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Sample records for preoperative imatinib therapy

  1. Positron emission tomography in patients with aggressive fibromatosis/desmoid tumours undergoing therapy with imatinib

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    Kasper, Bernd; Hohenberger, Peter [University of Heidelberg, Sarcoma Unit, ITM - Interdisciplinary Tumor Center Mannheim, Mannheim University Medical Center, Mannheim (Germany); Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig G. [German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

    2010-10-15

    We used {sup 18}F-FDG PET to evaluate the FDG uptake in patients with aggressive fibromatosis (AF, also known as desmoid tumours) undergoing therapy with imatinib (imatinib mesylate, Glivec). The pilot study included nine patients with progressive AF receiving oral treatment with imatinib at a daily dose of 800 mg. Patients were examined using PET prior to the start of therapy and during imatinib treatment. Restaging according to the Response Evaluation Criteria in Solid Tumors (RECIST) was performed in parallel using CT and/or MRI and served as reference. The clinical outcomes in nine evaluable patients were as follows: seven patients with stable disease, and two patients with progressive disease. A 27% decrease in the median average standardized uptake value (SUV) of the sequential PET examinations was demonstrated in all evaluable patients with three patients (33%) showing a decrease in SUV of more than 40% (48%, 52% and 54%, respectively); no patient showed a substantial increase in SUV. To our knowledge, this is the first series of AF patients undergoing treatment with imatinib and monitored using sequential PET imaging, that allows detection of SUV changes after imatinib induction, thus helping to decide whether treatment should be continued or not. (orig.)

  2. O tratamento da Leucemia Mielóide Crônica com mesilato de imatinibe Therapy of Chronic Myeloid Leukemia with imatinib mesylate

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    Vaneuza M. Funke

    2008-04-01

    Full Text Available O mesilato de imatinibe é atualmente o tratamento de escolha para pacientes com Leucemia mielóide Crônica (LMC recém-diagnosticados. Desde os primeiros estudos clínicos em 1998 até o estudo IRIS, que comparou o uso em primeira linha de imatinibe com interferon + ara-C, esta droga vem se consolidando em segurança e eficácia. Ainda há, entretanto questionamentos sobre a melhor dose inicial, a identificação dos pacientes que mais se beneficiariam e a melhor abordagem frente a respostas sub-ótimas e resistência. Os principais estudos clínicos publicados com mesilato de imatinibe são revisados no presente artigo, e discutidos sob a perspectiva da realidade brasileira.Imatinib mesylate is currently the gold-standard therapy for patients with newly diagnosed Chronic Myelogenous Leukemia. From the clinical trials in 1998 to the IRIS study, which compared first line imatinib treatment with interferon and low dose ara-C, this drug has been consolidated in regards to its safety and efficacy. There are still some questions to answer. Which would be the best initial dose? Are there any patients who benefit more than others? What is the best approach to suboptimal response and resistance? The most important published clinical studies are reviewed in the current article and discussed from a Brazilian perspective.

  3. Preoperative breast radiation therapy: Indications and perspectives

    DEFF Research Database (Denmark)

    Lightowlers, S V; Boersma, L J; Fourquet, A

    2017-01-01

    Preoperative breast radiation therapy (RT) is not a new concept, but older studies failed to change practice. More recently, there has been interest in revisiting preoperative RT using modern techniques. This current perspective discusses the indications, summarises the published literature and t...

  4. Surgery and imatinib therapy for liver oligometastasis of GIST: a study of Japanese Study Group on GIST.

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    Kanda, Tatsuo; Masuzawa, Toru; Hirai, Toshihiro; Ikawa, Osamu; Takagane, Akinori; Hata, Yasuhiro; Ojima, Hitoshi; Sodeyama, Harutsugu; Mochizuki, Izumi; Ishikawa, Takashi; Kagimura, Tatsuo; Nishida, Toshirou

    2017-04-01

    We conducted a multicenter prospective study to clarify the efficacy and safety of surgery and imatinib for liver oligometastasis of gastrointestinal stromal tumors. Eligible gastrointestinal stromal tumor patients were enrolled in the surgery trial or the imatinib trial. Primary endpoints were recurrence-free survival and progression-free survival, respectively. The trials were prematurely terminated due to amendment of guidelines for adjuvant imatinib therapy and low patient accrual. In the surgery trial, all the six patients showed hepatic recurrence: median recurrence-free survival was 145 days (range: 62-1366 days). Of the five patients receiving salvage imatinib therapy, two showed progressive disease although no death was observed. Of the five patients enrolled in the imatinib trial, one died of pneumonia after progressive disease, and four had not shown progressive disease as of last visit. The results suggest that liver oligometastasis of gastrointestinal stromal tumor may not be controllable by surgery alone and require concomitant imatinib therapy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Preoperative nutrition therapy - novel developments

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    Ljungqvist, Olle; Nygren, Jonas; Hausel, Jonatan; Thorell, Anders

    2000-01-01

    Elective surgery has until recently been performed in the overnight fasted state in order to reduce the risk of aspiration of gastric content during the induction of anaesthesia. However, in order to increase the preoperative well-being of surgical patients, most western countries have changed their routines during the last 10-15 years, allowing intake of clear fluids up to 2 hours before anaesthesia in most patients. Animal studies have demonstrated that undergoing different situations of st...

  6. Imatinib and gastrointestinal stromal tumor (GIST: a selective targeted therapy Imatinib y tumor del estroma gastrointestinal (GIST: un tratamiento selectivo frente a una diana molecular

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    A. Fernández

    2004-10-01

    Full Text Available Gastrointestinal stromal tumors are the most frequent mesenchymal tumors in the gastrointestinal tract. They originate from the interstitial cells of Cajal and are characterized by an anomalous receptor for a growth factor with tyrosine-kinase activity (c-kit. This anomaly causes a permanent activation of the receptor and uncontrolled cell growth. These tumors show a poor response to traditional chemotherapy drugs, and are thus associated with low survival in cases of advanced disease. Imatinib, a tyrosine kinase inhibitor, is an example of selective targeted oncologic therapy that induces improved survival in these patients. We discuss two cases of metastatic gastrointestinal stromal tumors with a good response to imatinib, and also review the pathophysiology and treatment-related outcome of this type of tumors. We include results from clinical phase-III studies.Los tumores del estroma gastrointestinal son los tumores mesenquimales más frecuentes del tracto digestivo y se originan de las células intersticiales de Cajal. Se caracterizan por presentar un receptor para el factor de crecimiento con actividad tirosin kinasa (c-kit anómalo que condiciona su activación permanente y un crecimiento celular incontrolado. Tienen una baja supervivencia en casos de enfermedad avanzada, con escasa respuesta a los agentes quimioterápicos tradicionales. El imatinib es un fármaco inhibidor de la tirosín kinasa y un ejemplo de terapia oncológica selectiva que condiciona un importante aumento en la supervivencia de estos pacientes. Se presentan 2 casos de enfermedad metastásica con buena respuesta a imatinib, así como una revisión sobre la fisiopatología y evolución en el tratamiento de este tipo de tumores, incluyendo resultados de estudios en fase III.

  7. Intravitreal Bevacizumab and Triamcinolone for Treatment of Cystoid Macular Oedema Associated with Chronic Myeloid Leukaemia and Imatinib Therapy

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    Eric K. Newcott

    2015-01-01

    Full Text Available Purpose. To evaluate the efficacy of intravitreal bevacizumab and triamcinolone in the treatment of cystoid macular oedema in a case with chronic myeloid leukaemia on imatinib treatment. Methods. We treated a 78-year-old man with bilateral cystoid macular oedema with intravitreal triamcinolone and subsequent bevacizumab in one eye and intravitreal bevacizumab, alone, in the fellow eye. Results. Serial intravitreal bevacizumab with and without triamcinolone treated cystoid macular oedema in both eyes and improved the vision. Conclusion. Intravitreal bevacizumab and triamcinolone could be viable options to treat cystoid macular oedema due to chronic myeloid leukaemia and imatinib therapy.

  8. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib

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    Ronan Swords

    2009-03-01

    Full Text Available Ronan Swords, Devalingam Mahalingam, Swaminathan Padmanabhan, Jennifer Carew, Francis GilesInstitute for Drug Development, Cancer Therapy and Research Centre, University of Texas Health Science Centre at San Antonio, USAAbstract: Chronic myeloid leukemia (CML is the consequence of a single balanced translocation that produces the BCR-ABL fusion oncogene which is detectable in over 90% of patients at presentation. The BCR-ABL inhibitor imatinib mesylate (IM has improved survival in all phases of CML and is the standard of care for newly diagnosed patients in chronic phase. Despite the very significant therapeutic benefits of IM, a small minority of patients with early stage disease do not benefit optimally while IM therapy in patients with advanced disease is of modest benefit in many. Diverse mechanisms may be responsible for IM failures, with point mutations within the Bcr-Abl kinase domain being amongst the most common resistance mechanisms described in patients with advanced CML. The development of novel agents designed to overcome IM resistance, while still primarily targeted on BCR-ABL, led to the creation of the high affinity aminopyrimidine inhibitor, nilotinib. Nilotinib is much more potent as a BCR-ABL inhibitor than IM and inhibits both wild type and IM-resistant BCR-ABL with significant clinical activity across the entire spectrum of BCR-ABL mutants with the exception of T315I. The selection of a second generation tyrosine kinase inhibitor to rescue patients with imatinib failure will be based on several factors including age, co-morbid medical problems and ABL kinase mutational profile. It should be noted that while the use of targeted BCR-ABL kinase inhibitors in CML represents a paradigm shift in CML management these agents are not likely to have activity against the quiescent CML stem cell pool. The purpose of this review is to summarize the pre-clinical and clinical data on nilotinib in patients with CML who have failed prior

  9. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib.

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    Swords, Ronan; Mahalingam, Devalingam; Padmanabhan, Swaminathan; Carew, Jennifer; Giles, Francis

    2009-09-21

    Chronic myeloid leukemia (CML) is the consequence of a single balanced translocation that produces the BCR-ABL fusion oncogene which is detectable in over 90% of patients at presentation. The BCR-ABL inhibitor imatinib mesylate (IM) has improved survival in all phases of CML and is the standard of care for newly diagnosed patients in chronic phase. Despite the very significant therapeutic benefits of IM, a small minority of patients with early stage disease do not benefit optimally while IM therapy in patients with advanced disease is of modest benefit in many. Diverse mechanisms may be responsible for IM failures, with point mutations within the Bcr-Abl kinase domain being amongst the most common resistance mechanisms described in patients with advanced CML. The development of novel agents designed to overcome IM resistance, while still primarily targeted on BCR-ABL, led to the creation of the high affinity aminopyrimidine inhibitor, nilotinib. Nilotinib is much more potent as a BCR-ABL inhibitor than IM and inhibits both wild type and IM-resistant BCR-ABL with significant clinical activity across the entire spectrum of BCR-ABL mutants with the exception of T315I. The selection of a second generation tyrosine kinase inhibitor to rescue patients with imatinib failure will be based on several factors including age, co-morbid medical problems and ABL kinase mutational profile. It should be noted that while the use of targeted BCR-ABL kinase inhibitors in CML represents a paradigm shift in CML management these agents are not likely to have activity against the quiescent CML stem cell pool. The purpose of this review is to summarize the pre-clinical and clinical data on nilotinib in patients with CML who have failed prior therapy with IM or dasatinib.

  10. Preoperative chemoradiation therapy for advanced rectal cancer

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    Tsujinaka, Toshimasa; Murotani, Masahiro; Iihara, Keisuke

    1997-01-01

    Preoperative concurrent chemoradiation therapy with 5-fluorouracil and cisplatin was applied for advanced rectal cancer. Eligible criteria were as follows: no previous treatment, more than hemicircular occupation, T 3 or more, invasion to adjacent organs or lymph node metastasis on CT scan, tumor fixation by digital examination. Eleven patients were enrolled with this regimen consisting of 5-FU; 500 mg/day x 5/w x 4, CDDP; 10 mg/day x 5/w x 4 and radiation; 2 Gy x 5/w x 4. As a toxicity, grade 2 leukopenia in 2 cases, grade 2 GI symptoms in one case and radiation dermatitis was observed in 8 cases. As a local response, there were PR in 10 cases and NC in 1 case. Surgical resection was performed on 8 patients. Histological responses in the resected specimens were grade 2, 5 cases; grade 1b, 1 case; and grade 1a, 2 cases. Operative radicalities were grade A, 3 cases; grade B, 3 cases; and grade C, 2 cases. Preoperative chemoradiation is one of the effective options in multimodal treatment for advanced rectal cancer. (author)

  11. 'Real-life' study of imatinib therapy in chronic phase-chronic myeloid leukemia: A novel retrospective observational longitudinal analysis.

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    Merante, Serena; Ferretti, Virginia; Elena, Chiara; Calvello, Celeste; Rocca, Barbara; Zappatore, Rita; Cavigliano, Paola; Orlandi, Ester

    2017-01-01

    Imatinib is a cornerstone of treatment of chronic myeloid leukemia. It remains unclear whether transient treatment discontinuation or dose changes affect outcome and this approach has not yet been approved for use outside clinical trials. We conducted a retrospective single-institution observational study to evaluate factors affecting response in 'real-life' clinical practice in 138 chronic myeloid leukemia patients in chronic phase treated with imatinib. We used a novel longitudinal data analytical model, with a generalized estimating equation model, to study BCR-ABL variation according to continuous standard dose, change in dose or discontinuation; BCR-ABL transcript levels were recorded. Treatment history was subdivided into time periods for which treatment was given at constant dosage (total 483 time periods). Molecular and cytogenetic complete response was observed after 154 (32%) and 358 (74%) time periods, respectively. After adjusting for length of time period, no association between dose and cytogenetic complete response rate was observed. There was a significantly lower molecular complete response rate after time periods at a high imatinib dosage. This statistical approach can identify individual patient variation in longitudinal data collected over time and suggests that changes in dose or discontinuation of therapy could be considered in patients with appropriate biological characteristics.

  12. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide

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    Dresemann, G.; Weller, M.; Ostenfeld-Rosenthal, Ann Maria

    2010-01-01

    A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor...

  13. Persistence of chromosomal abnormalities additional to the Philadelphia chromosome after Philadelphia chromosome disappearance during imatinib therapy for chronic myeloid leukemia.

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    Zaccaria, Alfonso; Valenti, Anna Maria; Donti, Emilio; Gozzetti, Alessandro; Ronconi, Sonia; Spedicato, Francesco

    2007-04-01

    Five Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) patients with additional chromosome abnormalities at diagnosis have been followed during Imatinib therapy. In all, the Ph chromosome disappeared, while the 5 cases, additional abnormalities [dup(1); del(5), +8 (2 patients) and +14] persisted in the subsequent studies, performed over a period of 11 to 49 months, either alone or together with a karyotypically normal cell population. This finding is consistent with a secondary origin of the Ph chromosome in these patients. It is still to early to evaluate the possible prognostic value of these additional abnormalities.

  14. Follow-up of hepatic and peritoneal metastases of gastrointestinal tumors (GIST) under Imatinib therapy requires different criteria of radiological evaluation (size is not everything!!!)

    International Nuclear Information System (INIS)

    Mabille, Mylene; Vanel, Daniel; Albiter, Marcela; Le Cesne, Axel; Bonvalot, Sylvie; Le Pechoux, Cecile; Terrier, Philippe; Shapeero, Lorraine G.; Dromain, Clarisse

    2009-01-01

    Purpose: To define computed tomography (CT) criteria for evaluating the response of patients with gastrointestinal stromal tumors (GIST) who are receiving Imatinib (tyrosine-kinase inhibitor therapy). Materials and methods: This prospective CT study evaluated 107 consecutive patients with advanced metastatic GIST treated with Imatinib. Results: Seventy patients had total or partial cystic-like transformation of hepatic and/or peritoneal metastases. These pseudocysts remained unchanged in size or stable in size on successive CT examinations (stable disease according to RECIST criteria). Forty-six patients developed metastases, 17 patients showed increasing parietal thickness and 29 patients with peripheral enhancing nodules. These CT changes represented local recurrence consistent with GIST resistance to Imatinib treatment. WHO or RECIST criteria did not provide a reliable evaluation of disease evolution or recurrence. Development of new enhancement of lesions (parietal thickness or nodule) was the only reliable criterion. Conclusion: The development of peripheral thickening or enhancing nodules within cystic-like metastatic lesions, even without any change in size, represented progressive GIST under Imatinib, growing in a short time and should alert the clinician for the possible need for a change in therapy

  15. Preoperative gemcitabine-based chemoradiation therapy for resectable pancreatic cancer

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    Takahashi, Hidenori; Ohigashi, Hiroaki; Goto, Kunihito; Marubashi, Shigeru; Yano, Masahiko; Ishikawa, Osamu

    2013-01-01

    During the period from 2002 to 2011, a total of 240 consecutive patients with resectable pancreatic cancer received preoperative chemoradiation therapy (CRT). Among 240 patients, 201 patients underwent the subsequent pancreatectomy (resection rate: 84%). The 5-year overall survival of resected cases was 56% and the median survival of 39 unresected cases was 11 months. The 5-year locoregional recurrence rate of resected cases was 15%. The 5-year overall survival of the entire cohort (n=240) was 47%. The preoperative CRT and subsequent pancreatectomy provided a favorable surgical result, which was contributed by several characteristics of preoperative CRT: the prominent locoregional treatment effect with lower incidence of locoregional recurrence, and the discrimination between patients who are likely to benefit from subsequent surgery and those who are not. (author)

  16. Oral rehydration therapy for preoperative fluid and electrolyte management.

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    Taniguchi, Hideki; Sasaki, Toshio; Fujita, Hisae

    2011-01-01

    Preoperative fluid and electrolyte management is usually performed by intravenous therapy. We investigated the safety and effectiveness of oral rehydration therapy (ORT) for preoperative fluid and electrolyte management of surgical patients. The study consisted of two studies, designed as a prospective observational study. In a pilot study, 20 surgical patients consumed 1000 mL of an oral rehydration solution (ORS) until 2 h before induction of general anesthesia. Parameters such as serum electrolyte concentrations, fractional excretion of sodium (FENa) as an index of renal blood flow, volume of esophageal-pharyngeal fluid and gastric fluid (EPGF), and patient satisfaction with ORT were assessed. In a follow-up study to assess the safety of ORT, 1078 surgical patients, who consumed ORS until 2 h before induction of general anesthesia, were assessed. In the pilot study, water, electrolytes, and carbohydrate were effectively and safely supplied by ORT. The FENa value was increased at 2 h following ORT. The volume of EPGF collected following the induction of anesthesia was 5.3±5.6 mL. In the follow-up study, a small amount of vomiting occurred in one patient, and no aspiration occurred in the patients. These results suggest that ORT is a safe and effective therapy for the preoperative fluid and electrolyte management of selected surgical patients.

  17. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide

    DEFF Research Database (Denmark)

    Dresemann, G.; Weller, M.; Ostenfeld-Rosenthal, Ann Maria

    2010-01-01

    A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor...... activity compared with HU monotherapy in the treatment of recurrent GBM. The target population consisted of patients with confirmed recurrent GBM and an Eastern Cooperative Oncology Group performance status of 0-2 who had completed previous treatment comprising surgical resection, irradiation therapy...

  18. ON012380: A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant CMLs

    National Research Council Canada - National Science Library

    Reddy, E. P

    2007-01-01

    Because it is now apparent that a significant proportion of patients chronically treated with imatinib develop resistance due to the acquisition of mutations in the kinase domain of BCR-ABL our aim...

  19. Preoperative depression symptom severity and its impact on adherence to preoperative beta-blocker therapy.

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    Schonberger, Robert B; Feinleib, Jessica; Holt, Natalie; Dai, Feng; Brandt, Cynthia; Burg, Matthew M

    2014-12-01

    To test the association among depression symptoms, distressed personality type, and preoperative beta-blocker nonadherence and to estimate the prevalence of untreated major depression in this population. Prospective observational study. A veterans hospital. One hundred twenty patients on outpatient beta-blocker therapy presenting for surgery. The Patient Health Questionnaire (PHQ)-9, the D-Scale-14 (DS14), and Modified Morisky Scale (MMS) questionnaires. Of 99 participants who presented for surgery, the incidence of preoperative nonadherence was 14.1% (95% confidence interval 7%-21%), consistent with prior research. Nonadherence was 9.5% among those with no depression, 27.8% among those with mild depression, and 28.6% among those with moderate-to-severe depression (Cochran-Armitage test for trend p = 0.03). Distressed personality type was found in 35% of the cohort (95% confidence interval 26-45%) and was not associated with beta-blocker nonadherence (Fisher's exact test, p = 0.24). Among participants with symptoms of major depressive disorder (n = 25, 25.3%), more than half (n = 14, 56%) had no indication of depression listed at their most recent primary care visit. Patients with symptoms of depression on chronic beta-blocker therapy are susceptible to medication nonadherence on the day of surgery. Most surgical patients with symptoms of major depression lack a diagnosis of depression. Preoperative depression screening may thus (1) identify a population at increased risk of beta-blocker withdrawal, and (2) identify patients who may benefit from anesthesiologist-initiated referral for this treatable condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Preoperative fluid and electrolyte management with oral rehydration therapy.

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    Taniguchi, Hideki; Sasaki, Toshio; Fujita, Hisae; Takamori, Mina; Kawasaki, Rieko; Momiyama, Yukinori; Takano, Osami; Shibata, Toshinari; Goto, Takahisa

    2009-01-01

    We hypothesized that oral rehydration therapy using an oral rehydration solution may be effective for preoperative fluid and electrolyte management in surgical patients before the induction of general anesthesia, and we investigated the safety and effectiveness of oral rehydration therapy as compared with intravenous therapy. Fifty female patients who underwent breast surgery were randomly allocated to two groups. Before entry to the operation room and the induction of general anesthesia, 25 patients drank 1000 ml of an oral rehydration solution ("oral group") and 25 patients were infused with 1000 ml of an intravenous electrolyte solution ("intravenous group"). Parameters such as electrolyte concentrations in serum and urine, urine volume, vital signs, vomiting and aspiration, volumes of esophageal-pharyngeal fluid and gastric fluid (EPGF), and patient satisfaction with the therapy (as surveyed by a questionnaire) were assessed. After treatment, the serum sodium concentration and the hematocrit value, which both declined within the normal limits, were significantly higher in the oral group than in the intravenous group (sodium, 140.8 +/- 2.9 mEq x l(-1) in the oral group and 138.7 +/- 1.9 mEq x l(-1) in the intravenous group; P = 0.005; hematocrit, 39.03 +/- 4.16% in the oral group and 36.15 +/- 3.41% in the intravenous group; P = 0.01). No significant difference was observed in serum glucose values. Urine volume was significantly larger in the oral group (864.9 +/- 211.5 ml) than in the intravenous group (561.5 +/- 216.0 ml; P rehydration therapy, as judged by factors such as "feeling of hunger", "occurrence of dry mouth", and "less restriction in physical activity". The volume of EPGF collected following the induction of anesthesia was significantly smaller in the oral group than in the intravenous group (6.03 +/- 9.14 ml in the oral group and 21.76 +/- 30.56 ml in the intravenous group; P rehydration therapy with an oral rehydration solution before surgery is

  1. Do polymorphisms in MDR1 and CYP3A5 genes influence the risk of cytogenetic relapse in patients with chronic myeloid leukemia on imatinib therapy?

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    Harivenkatesh, Natarajan; Kumar, Lalit; Bakhshi, Sameer; Sharma, Atul; Kabra, Madhulika; Velpandian, Thirumurthy; Gogia, Ajay; Shastri, Shivaram S; Gupta, Yogendra Kumar

    2017-09-01

    Influence of polymorphisms in the genes coding for imatinib transporters and metabolizing enzymes on cytogenetic relapse in patients with chronic myeloid leukemia (CML) is not known. One hundred and four patients (52 cases with cytogenetic relapse and 52 controls without relapse) with chronic-phase CML on imatinib therapy and have completed 5 years of follow-up were enrolled. The following single nucleotide polymorphisms (SNPs) were genotyped; C1236T, C3435T, G2677T/A in MDR1 gene and A6986G in CYP3A5 gene, using PCR-RFLP method and validated by direct gene sequencing. Imatinib trough levels were measured using LC-MS/MS. Patients with CC genotype for MDR1-C1236T polymorphism were at significantly higher risk for cytogenetic relapse [OR =4.382, 95% CI (1.145, 16.774), p = .022], while those with TT genotype for MDR1-C3435T polymorphism had significantly lower risk of relapse [OR =0.309, 95% CI (0.134, 0.708), p = .005]. Imatinib trough levels were lower in patients with relapse compared to those without relapse (1551.4 ± 1324.1 vs. 2154.2 ± 1358.3 ng/mL; p = .041). MDR1-C3435T genotype [adjusted-OR: 0.266; 95% CI (0.111, 0.636); p = .003] and trough levels (p = .014) were independent predictors of relapse in multivariate analysis. To conclude, C1236T and C3435T polymorphisms in MDR1 gene and trough levels significantly influence the risk of cytogenetic relapse. MDR1-C3435T genotype might emerge as a potential biomarker to predict the risk of cytogenetic relapse in patients with CML.

  2. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer

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    Rich, T.A.; Skibber, J.M.; Ajani, J.A. [Univ. of Texas M. D. Anderson Cancer Center, Houston, TX (United States)] [and others

    1995-07-15

    To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m{sup 2}/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. Posttreatment tumor stages were T1-2, N0 in 35%, T3, N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further. 22 refs., 2 figs., 3 tabs.

  3. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study

    International Nuclear Information System (INIS)

    Rutkowski, Piotr; Osuch, Czesław; Mierzejewska, Ewa; Wasielewski, Kacper; Woźniak, Agnieszka; Grzesiakowska, Urszula; Nowecki, Zbigniew I; Siedlecki, Janusz A; Limon, Janusz; Bylina, Elżbieta; Klimczak, Anna; Świtaj, Tomasz; Falkowski, Sławomir; Kroc, Jacek; Ługowska, Iwona; Brzeskwiniewicz, Magdalena; Melerowicz, Wojciech

    2012-01-01

    Gastrointestinal stromal tumors (GIST) mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM) or sunitinib (SU). Arterial hypertension (AH) is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+) GIST patients after IM failure. We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2 nd line treatment). Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs) of VEGFA and VEGFR2 genes. One year progression-free survival (PFS; calculated from the start of SU) rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM) was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks) in 55 patients with AH vs. 22% (median 17 weeks) in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively) than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively). We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism (OR: 10.0 p = 0.041 and OR: 10.5; p = 0

  4. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST after imatinib failure - one institution study

    Directory of Open Access Journals (Sweden)

    Rutkowski Piotr

    2012-03-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM or sunitinib (SU. Arterial hypertension (AH is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+ GIST patients after IM failure. Methods We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2nd line treatment. Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs of VEGFA and VEGFR2 genes. Results One year progression-free survival (PFS; calculated from the start of SU rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks in 55 patients with AH vs. 22% (median 17 weeks in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively. We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism

  5. Sphincter preservation with preoperative radiation therapy and coloanal anastomosis

    Energy Technology Data Exchange (ETDEWEB)

    Minsky, Bruce D; Cohen, Alfred M; Enker, Warren E; Paty, Philip

    1995-02-01

    Purpose: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. Methods and Materials: Thirty patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (2: T2, 28: T3) involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (range: 1.5-6 cm) and the median distance from the anal verge was 4 cm (range: 3-7 cm). The whole pelvis received 46.8 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 43 months (range: 6-82 months). Results: Of the 29 patients who underwent resection, 3 (10%) had a complete pathologic response and 24 (83%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 4-year actuarial: 23%. The 4-year actuarial survival was 75%. One patient developed a partial disruption of the anastomosis and two developed rectal stenosis. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in 22 of the 24 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 77%. The median number of bowel movements/day was two (range: 1-6). Conclusions: This technique may be an alternative to an abdominoperineal resection in selected patients. Continued follow-up is needed to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection.

  6. Sphincter preservation with preoperative radiation therapy and coloanal anastomosis

    International Nuclear Information System (INIS)

    Minsky, Bruce D.; Cohen, Alfred M.; Enker, Warren E.; Paty, Philip

    1995-01-01

    Purpose: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. Methods and Materials: Thirty patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (2: T2, 28: T3) involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (range: 1.5-6 cm) and the median distance from the anal verge was 4 cm (range: 3-7 cm). The whole pelvis received 46.8 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 43 months (range: 6-82 months). Results: Of the 29 patients who underwent resection, 3 (10%) had a complete pathologic response and 24 (83%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 4-year actuarial: 23%. The 4-year actuarial survival was 75%. One patient developed a partial disruption of the anastomosis and two developed rectal stenosis. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in 22 of the 24 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 77%. The median number of bowel movements/day was two (range: 1-6). Conclusions: This technique may be an alternative to an abdominoperineal resection in selected patients. Continued follow-up is needed to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection

  7. ON012380: A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant CMLs

    Science.gov (United States)

    2010-05-01

    imatinib resistance with a novel ABL kinase inhibitor. Science. 2004; 305(5682):399-401 3. Weisberg E, Manley PW, Breitenstein W, Bruggen J, Cowan-Jacob... Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid...araldehyde (5) (10 mmol), glacial acetic acid (5 mL), and a catalytic amount (100 lL ) of benzyl amine was re- fluxed for 5–8 h. After completion of

  8. Difficult Myotomy Is Not Determined by Preoperative Therapy and Does Not Impact Outcome

    OpenAIRE

    Cowgill, Sarah M.; Villadolid, Desiree V.; Al-Saadi, Sam; Rosemurgy, Alexander S.

    2007-01-01

    Objectives: The impact of preoperative endoscopic therapy on the difficulty of laparoscopic Heller myotomy and the impact of the difficulty of the myotomy on long-term outcome has not been determined. This study was undertaken to determine whether preoperative therapy impacts the difficulty of laparoscopic Heller myotomy and whether preoperative therapy or difficulty of myotomy impacts long-term outcomes. Methods: Since 1992, 305 patients, 56% male, median age 49 years, underwent laparoscopic...

  9. Dasatinib rapidly induces deep molecular response in chronic-phase chronic myeloid leukemia patients who achieved major molecular response with detectable levels of BCR-ABL1 transcripts by imatinib therapy.

    Science.gov (United States)

    Shiseki, Masayuki; Yoshida, Chikashi; Takezako, Naoki; Ohwada, Akira; Kumagai, Takashi; Nishiwaki, Kaichi; Horikoshi, Akira; Fukuda, Tetsuya; Takano, Hina; Kouzai, Yasuji; Tanaka, Junji; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

    2017-10-01

    With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment. In the present study, we attempted to investigate whether switching the treatment from imatinib to dasatinib can induce DMR in 16 CP-CML patients treated with imatinib for at least two years who achieved a major molecular response (MMR) with detectable levels of BCR-ABL1 transcripts. The rates of achievement of DMR at 1, 3, 6 and 12 months after switching to dasatinib treatment in the 16 patients were 44% (7/16), 56% (9/16), 63% (10/16) and 75% (12/16), respectively. The cumulative rate of achieving DMR at 12 months from initiation of dasatinib therapy was 93.8% (15/16). The proportion of natural killer cells and cytotoxic T cells in peripheral lymphocytes increased after switching to dasatinib. In contrast, the proportion of regulatory T cells decreased during treatment. The safety profile of dasatinib was consistent with previous studies. Switching to dasatinib would be a therapeutic option for CP-CML patients who achieved MMR but not DMR by imatinib, especially for patients who wish to discontinue TKI therapy.

  10. Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

    Science.gov (United States)

    Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

    2014-01-01

    Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

  11. Preoperative radiation therapy for muscle-invading bladder carcinoma

    International Nuclear Information System (INIS)

    Cox, J.A.; Greven, K.M.; Anscher, M.S.; Morgan, T.M.; Scott, J.

    1991-01-01

    This paper reports on low-dose and high-dose radiation therapy (RT) followed by cystectomy for bladder carcinoma that was evaluated for survival, failure patterns, and complications as these outcomes have been incompletely documented in the past. One hundred five patients with clinical stages T2-T4 (muscle-invading) transitional cell carcinoma of the bladder who completed preoperative RT followed by total cystectomy were evaluated. Eighty-five patients received 20-27 Gy in 4-7 fractions (group A). Twenty patients received 40-50 Gy in 20-28 fractions (group B). Actuarial 5-year survival was 45% and 29% (P = .06) for groups A and B, respectively; 6% of group A was stage T4 compared with 30% of group B. Five-year actuarial survival for patients with stages T2-T3 in groups A and B was 46% and 42%, respectively, while that for T4 was 33% and 0% in groups A and B, respectively. Multivariate analysis revealed that stage, grade, and presence of hydronephrosis independently affected survival. Five-year actuarial local control rates for T2, T3, and T4 were 93%, 93%, and 22%, respectively, with no significant difference between RT groups. Rates of distant metastasis and complications versus preoperative regime and stage were similar

  12. Preoperative combination therapy of 5-fluorouracil suppository and radiation for carcinoma of the rectum

    International Nuclear Information System (INIS)

    Mizusawa, Hirokazu; Takahashi, Toshio

    1983-01-01

    Twelve cases of carcinoma of the rectum were treated preoperatively by combination therapy with 5-fluorouracil (5-FU) suppository (100 mg twice a day consecutively, a total dose of more than 4,000 mg) and irradiation (300 rad x 3/week, a total dose of 3,000 rad). This group was compared with 34 cases given single preoperative 5-FU therapy and 24 control cases given no preoperative adjuvant modality. The group treated by preoperative combination therapy showed marked antitumor effects macroscopically and histologically. In addition, decrease in local recurrence was expected for this group, compared with the other two groups. (Chiba, N.)

  13. Combined preoperative therapy for oral cancer with nedaplatin and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Masatoshi; Shibata, Akihiko; Hayashi, Munehiro [Nippon Dental Univ., Tokyo (Japan). Hospital] (and others)

    2002-03-01

    We performed preoperative combined therapy using nedaplatin (CDGP) and radiation in 12 patients with squamous cell carcinoma originating from the oral cavity and maxillary sinus, and examined for any adverse events that may have occurred during this therapeutic regimen. Regarding the irradiation, external irradiation utilizing a 6 MV linac (linear accelerator) at a dose of 2.0 Gy/day was performed 5 times a week, with the target total radiation dose set at 40 Gy. In addition, CDGP was intravenously administered 30 minutes before irradiation at a dose of 5 mg/m{sup 2}/day. Mucositis was observed in all 12 subjects, however, the severity was observed to be grade 1-2 with no major differences in comparison to the patients given standard radiation monotherapy. Two subjects developed grade 3 leucopenia and were thus given granulocyte colony stimulating factor (G-CSF). In addition, grade 2 and grade 3 thrombocytopenia were both observed in one subject each. The subject with grade 3 thrombocytopenia required a platelet transfusion during surgery. No marked changes in serum creatinine levels were noted. These findings are therefore considered to provide evidence supporting the safety of this combination therapy. (author)

  14. Preoperative radiation therapy and iododeoxyuridine for large retroperitoneal sarcomas

    International Nuclear Information System (INIS)

    Robertson, John M.; Sondak, Vernon K.; Weiss, Sharon A.; Sussman, Jeffrey J.; Chang, Alfred E.; Lawrence, Theodore S.

    1995-01-01

    Purpose: Local failure is frequent after conventional therapy for patients with retroperitoneal sarcomas. A Phase I/II multimodality approach was used, combining iododeoxyuridine (IdUrd) and radiation therapy, followed by attempted surgical resection, with the goal of improving local control. Methods and Materials: Patients with retroperitoneal sarcomas were treated with three to five consecutive cycles of treatment. Each 14-day cycle consisted of a continuous intravenous infusion of IdUrd on days 1-5, twice a day radiation therapy (1.25 Gy/fraction) on days 8-12, and a break on day 13 and 14. Surgical resection was attempted after three or five cycles. Patients resected after three cycles received an additional two cycles of treatment with radiation directed to the tumor bed. IdUrd dose was escalated in Phase I fashion (1000 mg/m 2 /day, 1333 mg/m 2 /day, and 1600 mg/m 2 /day). The median potential follow-up was 31 months. Results: Sixteen patients (13 with high grade tumors) were treated. The median maximum tumor size was 17 cm. Resection margins were negative in four patients, microscopically positive in four patients, and grossly positive in three patients. Five patients were not resected. The only grade 4 acute toxicity observed was vomiting which occurred in three patients receiving upper abdominal radiation. Postsurgical and long-term complications were rare. Median survival overall and for resected patients were 18 and 32 months, respectively. Local control was observed in three out of four patients with negative margins (9, 40+, and 51+ months), two out of four patients with microscopically positive margins (4 and 22 months), and one out of three patients with grossly positive margins (46+ months). The overall freedom from local progression was 45% at 24 months. Conclusion: Retroperitoneal sarcomas can be resected after preoperative radiation therapy and IdUrd, with encouraging local control in patients resected with negative or microscopically positive

  15. Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Ramchandren

    2009-05-01

    Full Text Available Radhakrishnan Ramchandren, Charles A SchifferDivision of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USAAbstract: The development of imatinib for the treatment of chronic myeloid leukemia (CML has proven to be an example of medical success in the era of targeted therapy. However, imatinib resistance or intolerance occurs in a substantial number of patients. Additionally, patients who have progressed beyond the chronic phase of CML do relatively poorly with imatinib therapy. Mechanisms of imatinib resistance include BCR-ABL point mutations resulting in decreased imatinib binding, as well as mutation-independent causes of resistance such as SRC family kinase dysregulation, BCR-ABL gene amplification, drug influx/efflux mechanisms and other poorly understood processes. The options for therapy in these patients include stem cell transplantation, imatinib dose escalation as well as the use of second-generation tyrosine kinase inhibitors. Dasatinib is a second-generation multi-kinase inhibitor with several theoretical and mechanistic advantages over imatinib. Moreover, several studies have evaluated dasatinib in patients who have progressed on imatinib therapy with encouraging results. Other novel agents such as mTOR inhibitors, bosutinib and INNO 406 have also shown promise in this setting. Although treatment options have increased, the choice of second-line therapy in patients with CML is influenced by concerns surrounding the duration of response as well as toxicity. Consequently, there is no agreed upon optimal second-line agent. This paper reviews the current data and attempts to address these issues. Keywords: chronic myeloid leukemia (CML, dasatinib, imatinib, resistance (imatinib resistance, nilotinib, tyrosine kinase inhibitor

  16. Imatinib-induced postoperative periorbital purpura: GASP (Gleevec-Associated Surgical Purpura) in a woman with imatinib-treated chronic myelogenous leukemia.

    Science.gov (United States)

    Anzalone, C Lane; Cohen, Philip R; Kurzrock, Razelle; Cortes, Jorge E

    2014-01-15

    Imatinib mesylate is a selective tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukemia. Ocular side effects of imatinib include periorbital edema, which may become so severe as to obstruct the visual field. The purpose of this case study is to describe the clinical characteristics of imatinib- induced postoperative periorbital purpura. We retrospectively reviewed the medical literature using PubMed, searching the terms edema, Gleevec, imatinib, periorbital, postoperative and purpura. Patient reports and previous reviews of the subject were critically assessed and the salient features are presented. Three patients have undergone surgery to reduce the imatinib-induced periorbital edema; two of these individuals have developed imatinib-induced postoperative periorbital purpura. We recommend discontinuing imatinib usage one week prior to periorbital surgery and not resuming therapy until the eighth postoperative day.

  17. Difficult Myotomy Is Not Determined by Preoperative Therapy and Does Not Impact Outcome

    Science.gov (United States)

    Villadolid, Desiree V.; Al-Saadi, Sam; Rosemurgy, Alexander S.

    2007-01-01

    Objectives: The impact of preoperative endoscopic therapy on the difficulty of laparoscopic Heller myotomy and the impact of the difficulty of the myotomy on long-term outcome has not been determined. This study was undertaken to determine whether preoperative therapy impacts the difficulty of laparoscopic Heller myotomy and whether preoperative therapy or difficulty of myotomy impacts long-term outcomes. Methods: Since 1992, 305 patients, 56% male, median age 49 years, underwent laparoscopic Heller myotomy and were prospectively followed. The difficulty of the laparoscopic Heller myotomy was scored by the operating surgeon for the most recent 170 consecutive patients on a scale of 1 (easiest) to 5 (most difficult). Patients scored their symptoms before and after myotomy using a Likert scale from 0 (never/not bothersome) to 10 (always/very bothersome). Results: Before myotomy, 66% of patients underwent endoscopic therapy: 33% dilation, 11% Botox, and 22% both. Preoperative endoscopic therapy did not correlate with the difficulty of the myotomy (P=NS). Median follow-up was 25 months. Regardless of the difficulty of the myotomy, dysphagia improved with myotomy (Pmyotomy. Conclusions: Laparoscopic Heller myotomy improves the frequency and severity of dysphagia. The difficulty of laparoscopic Heller myotomy is not impacted by preoperative therapy, and neither preoperative therapy nor difficulty of the myotomy impact long-term outcome. PMID:17931516

  18. [New orientations in the management of advanced, metastatic gastrointestinal stromal tumors (GIST): combination of surgery and systemic therapy with imatinib in a case of primary gastric location].

    Science.gov (United States)

    Catani, Marco; De Milito, Ritanna; Simi, Mario

    2005-01-01

    the spleen, the transverse colon and the distal pancreatic tract. The neoplasm was directly linked to the left liver and to the inferior diaphragmatic surface. We performed total gastrectomy and resection of the tail of the pancreas, the spleen, and the transverse colon all in one and the same session. The patient was discharged on postoperative day 8 and commenced imatinib therapy 30 days after the operation with 4 tablets per day. In the following months the patient repeated the CT scan to monitor the progressive volume reduction of the liver and lung lesions and a PET scan confirmed that the lesions were not active; the patient experienced a 13 kg body weight increase. One year after the operation the outcome appears to be lasting and the patient has tolerated the drug treatment well.

  19. Myeloid Neoplasms with t(5;12 and ETV6-ACSL6 Gene Fusion, Potential Mimickers of Myeloid Neoplasm with PDGFRB Rearrangement: Case Report with Imatinib Therapy and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Javier De Luca-Johnson

    2016-01-01

    Full Text Available We report the second case of ETV6-ACSL6 associated myeloproliferative neoplasm that has received a full course of imatinib therapy. The patient was a 51-year-old previously healthy man who presented with three months of worsening dyspnea and was found to have a white count of 216,000/cmm, of which 84% were eosinophil lineage. Cytogenetic analysis revealed a t(5;12(q31~33;p13. FISH was negative for PDGFRB rearrangement but additional FISH testing demonstrated an ACSL6 rearrangement. ETV6-ACSL6 gene fusion is a rare abnormality that most often presents as a myeloproliferative-type disorder with prominent eosinophilia or basophilia. Review of the literature yielded a total of 11 previous cases. This gene fusion results in a t(5;12(q31~33;p13 that mimics the t(5;12 found in ETV6-PDGFRB neoplasms. Identification of the fusion genes involved in t(5;12 in eosinophilia-associated myeloproliferative disorders is crucial to direct an effective treatment plan. In particular, while tyrosine kinase inhibitor therapy is effective in patients with PDGFRB rearrangement, there is little information on imatinib efficacy in patients with ETV6-ACSL6 gene fusion. Our patient was found to be nonresponsive to imatinib therapy.

  20. Profile of imatinib in pediatric leukemia

    Directory of Open Access Journals (Sweden)

    Burke MJ

    2014-02-01

    Full Text Available Michael J BurkeDepartment of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI, USAAbstract: Using targeted therapy for treatment of cancer has become the paradigm to which clinical trials aspire. Imatinib, the BCR-ABL1 tyrosine kinase inhibitor (TKI, was the first of its kind to specifically target and inhibit the underlying Philadelphia chromosome (Ph+ oncogene found to be driving chronic myeloid leukemia in adults, and has since become standard of care for the treatment of chronic myeloid leukemia in children. Imatinib, with its ability to target Ph+ leukemia, has been successfully incorporated into the treatment of not only pediatric chronic myeloid leukemia but also Ph+ acute lymphoblastic leukemia. With the incorporation of imatinib into combination chemotherapy for pediatric Ph+ acute lymphoblastic leukemia, current survival rates are far higher than at any other time for this once dreadful disease. With more children today receiving treatment with imatinib for either chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia, knowledge is accumulating surrounding the short-term and long-term toxicities observed in children, adolescents, and young adults treated with this TKI. In summary, the TKI imatinib has made a historic impact in the treatment of pediatric Ph+ leukemias, transforming what were once very high-risk diseases with considerable morbidity and mortality into ones that are now very treatable but with a new awareness surrounding the long-term toxicities that may come with this price for cure.Keywords: imatinib, leukemia, lymphoblastic leukemia, chronic myeloid leukemia, pediatric

  1. Preoperative Therapy for Lower Rectal Cancer and Modifications in Distance From Anal Sphincter

    International Nuclear Information System (INIS)

    Gavioli, Margherita; Losi, Lorena; Luppi, Gabriele; Iacchetta, Francesco; Zironi, Sandra; Bertolini, Federica; Falchi, Anna Maria; Bertoni, Filippo; Natalini, Gianni

    2007-01-01

    Purpose: To assess the frequency and magnitude of changes in lower rectal cancer resulting from preoperative therapy and its impact on sphincter-saving surgery. Preoperative therapy can increase the rate of preserving surgery by shrinking the tumor and enhancing its distance from the anal sphincter. However, reliable data concerning these modifications are not yet available in published reports. Methods and Materials: A total of 98 cases of locally advanced cancer of the lower rectum (90 Stage uT3-T4N0-N+ and 8 uT2N+M0) that had undergone preoperative therapy were studied by endorectal ultrasonography. The maximal size of the tumor and its distance from the anal sphincter were measured in millimeters before and after preoperative therapy. Surgery was performed 6-8 weeks after therapy, and the histopathologic margins were compared with the endorectal ultrasound data. Results: Of the 90 cases, 82.5% showed tumor downsizing, varying from one-third to two-thirds or more of the original tumor mass. The distance between the tumor and the anal sphincter increased in 60.2% of cases. The median increase was 0.73 cm (range, 0.2-2.5). Downsizing was not always associated with an increase in distance. Preserving surgery was performed in 60.6% of cases. It was possible in nearly 30% of patients in whom the cancer had reached the anal sphincter before the preoperative therapy. The distal margin was tumor free in these cases. Conclusion: The results of our study have shown that in very low rectal cancer, preoperative therapy causes tumor downsizing in >80% of cases and in more than one-half enhances the distance between the tumor and anal sphincter. These modifications affect the primary surgical options, facilitating or making sphincter-saving surgery possible

  2. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Science.gov (United States)

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  3. Improving breast cancer outcome by preoperative systemic therapy and image-guided surgery

    NARCIS (Netherlands)

    Mieog, Jan Sven David

    2011-01-01

    This thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to achieve improved surgical options and to assess tumor response. We also demonstrated that

  4. Hepatic stellate cell-targeted imatinib nanomedicine versus conventional imatinib: A novel strategy with potent efficacy in experimental liver fibrosis.

    Science.gov (United States)

    El-Mezayen, Nesrine S; El-Hadidy, Wessam F; El-Refaie, Wessam M; Shalaby, Th I; Khattab, Mahmoud M; El-Khatib, Aiman S

    2017-11-28

    Liver fibrosis is a global health problem without approved treatment. Imatinib inhibits two key profibrotic pathways; platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) and thus can be used to treat liver fibrosis. However, conventional imatinib therapy is hampered by low concentration at target tissue and increased toxicity to other tissues especially heart, lung and liver. Since hepatic stellate cells (HSCs) are the main contributors to liver fibrosis pathogenesis and sole hepatic vitamin A (V A ) storage cells, they can be actively targeted by coupling liposomes to V A . In this study, novel V A -coupled imatinib-loaded liposomes (ILC) were prepared and optimized regarding V A -coupling efficiency, imatinib entrapment efficiency, and particle size. Preferential accumulation of the selected formula in liver was proved by tracing intraperitoneally (i.p.)-injected V A -coupled liposomes loaded with Nile Red (LCNR) to rats with CCl 4 -induced liver fibrosis using live animal imaging. Co-localization of LCNR with immunofluorescently-labeled PDGFR-β in frozen liver tissue sections confirmed HSCs targeting. ILC bio-distribution, following single i.p. injection, revealed 13.5 folds higher hepatic accumulation than conventional imatinib in addition to limited bio-distribution to other organs including heart and lung reflecting diminished adverse effects. ILC therapy resulted in a potent inhibition of phosphorylated PDGFR-β expression when compared to conventional imatinib. Subsequently, there was a statistically significant improvement in liver function tests and reversal of hepatotoxicity along with liver fibrosis. Anti-fibrotic effect was evident from histopathologic Ishak score reduction as well as normalization of the level of profibrotic mediators (hydroxyproline, TGF-B and matrix metalloproteinase-2). Thus, HSC-targeted imatinib therapy shows outstanding anti-fibrotic effects with reduced cytotoxicity compared to conventional

  5. Non-Hodgkin's lymphoma in a chronic myelocytic leukemia patient treated with imatinib

    Directory of Open Access Journals (Sweden)

    Semra Paydaş

    2011-09-01

    Full Text Available Imatinib is an important example of tyrosine kinase inhibitors (TKIs used in clinical practice. Imatinib blocks the ATP binding site of the Bcr-Abl fusion protein and selectively inhibits Bcr-Abl tyrosine kinase (TK activity. Treatment of chronic myelocytic leukemia (CML with imatinib is encouraging and it has an acceptable toxicity profile, and as such has changed the management of CML during the last decade. As with all drugs used in clinical practice, side effects of imatinib have been reported in studies with extended follow-up periods. In addition, some neoplastic disorders have been reported to occur during imatinib therapy. Herein we present a CML case that developed non-Hodgkin’s lymphoma (NHL while receiving imatinib treatment.

  6. Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Wang, Dian [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Haas, Rick L.M. [Department of Radiotherapy, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Catton, Charles N. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Indelicato, Daniel J. [Department of Radiation Oncology, University of Florida Medical Center, Jacksonville, Florida (United States); Kirsch, David G. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Roberge, David [Department of Radiation Oncology, Centre Hospitalier de l' Université de Montreal, Montreal, Quebec (Canada); Salerno, Kilian [Department of Radiation Oncology, Roswell Park Cancer Institute, Buffalo, New York (United States); Deville, Curtiland [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Sidney Kimmel Cancer Center, Washington, DC (United States); Guadagnolo, B. Ashleigh [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); O' Sullivan, Brian [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Petersen, Ivy A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Le Pechoux, Cecile [Department of Radiotherapy, Institut Gustave-Roussy, Villejuif (France); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-07-01

    Purpose: Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. Methods and Materials: An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available. Results: Treatment guidelines for preoperative RT for RPS are presented. Conclusions: An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy

  7. Oral Effects and Early Implant Survival Results After Imatinib Discontinuation Therapy for Chronic Myelogenous Leukemia: A Case Report.

    Science.gov (United States)

    Dixon, Douglas R; Yassin, Alaa

    2017-08-01

    Little is known regarding the success, failure, or complication rates of advanced implant procedures in patients after discontinuation therapy of long-term medications for the treatment of chronic myelogenous leukemia (CML). This case report presents initial results of a case involving implant placement in the mandible and maxilla as well as reduction of palatal oral pigmentation in a patient discontinuing long-term tyrosine kinase inhibitor (TKI) therapy for CML. A 57-year-old male was referred to the Department of Periodontics, University of Washington, Seattle, Washington, for an assessment of edentulous areas (tooth sites #3 and #14) and failing tooth #19. Previous medical treatment included oral administration (>10 years) of TKI for the treatment of CML. Systemic complications arising from long-term TKI therapy were treated with discontinuation of this medication. Concurrently, after multispecialty dental and medical consultation, extraction of tooth #19 with immediate implant placement and bilateral sinus augmentation with simultaneous implant placement were successfully performed during three separate surgical appointments. Additionally, marked reduction of oral palatal pigmentation was observed during the surgical and restorative phases after TKI discontinuation. Patients with a history of long-term TKIs for CML are at risk for developing complications that result in discontinuation of therapy. Long-term benefits of therapy may allow these patients to enjoy remission with an extended and improved quality of life. Patients undergoing discontinuation therapy may seek dental care. Therefore, dental providers need to understand these systemic interactions and, with multispecialty consultation, may help effectively treat these individuals.

  8. Preoperative combination therapy of 5-fluorouracil suppository and radiation for carcinoma of the rectum

    International Nuclear Information System (INIS)

    Mizusawa, Hirokazu

    1986-01-01

    The effect of adjuvant preoperative treatments with radiation and 5-fluorouracil (5-FU) on rectal carcinomas was investigated. The radiation therapy was administered in the area including the rectum and regional lymph nodes up to the level of the promontorium with 10 doses of 300 rad in three-week periods (a total dose of 3,000 rad). The suppository containing 100 mg of 5-FU was given intrarectally twice daily in the same period (a total dose of 4,000 mg of 5-FU). The surgical procedure with either abdominoperineal excision or anterior resection was performed within 14 days after the last preoperative treatment. The resected specimens were examined microscopically. The mean thickness of excised tumor-free tissue around the rectal wall having the most extended tumor growth was 6.2 mm in 16 patients receiving the treatment with radiation and 5-FU, 3.9 mm in 31 patients with 5-FU alone and 3.7 mm in 19 patients without preoperative treatments. Lymph node metastases were detected in 3 of 17 patients (19 %) with radiation and 5-FU, in 18 of 33 patients (55 %) with 5-FU alone, and in 11 of 24 patients (46 %) without preoperative treatments. The extensive degenerative pictures of cancer cells such as nuclear picnosis, and the growth of collagen fibers in carcinoma foci were observed in resected specimens with radiation and 5-FU treatments. Those findings suggest that preoperative adjuvant therapy with moderate dose of radiation and 5-FU affected significantly rectal carcinomas. There were no adverse effects. It seems likely, thus, that this combined therapy could prevent postoperative local or intrapelvic recurrence, which was the most frequent form of recurrence after curative surgery in rectal cancer. (author)

  9. [Use of laser- and extremely high frequency magnetic therapy in the preoperative period before diskectomy].

    Science.gov (United States)

    Miriotova, N F; Levitskiĭ, E F; Stupak, I N; Serebrennikov, A N

    2002-01-01

    Electromagnetic therapy and tractions contributed to reduction of neurovascular structures compression evident not only from regression of clinical symptoms but also from improvement of regional hemodynamics, functional condition of the affected nerves and muscles of the limbs. This prediscectomy preparation appeared an effective conservative treatment for 69% patients. The rest patients benefited from such preoperative preparation which provided stabilization of the patients' condition before and after dyscectomy.

  10. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarty, Twisha; Crane, Christopher H. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mansfield, Paul F. [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Briere, Tina M.; Beddar, A. Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  11. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    International Nuclear Information System (INIS)

    Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.; Mansfield, Paul F.; Briere, Tina M.; Beddar, A. Sam; Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E.; Das, Prajnan

    2012-01-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92–1.01). The median V 30 (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V 20 (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V 40 (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate pathologic

  12. Comparison of preoperative and postoperative radiation therapy for patients with carcinoma of head and neck

    International Nuclear Information System (INIS)

    Snow, J.B.; Gelber, R.D.; Kramer, S.; Davis, L.W.; Marcial, V.A.; Lowry, L.D.

    1981-01-01

    Three hundred and fifty-four patients with squamous cell carcinoma of the oral cavity, oropharynx, supraglottic larynx, hypopharynx or maxillary sinus have been randomized for preoperative radiation therapy and surgery versus surgery and postoperative radiation therapy plus, in the case of patients with lesions of the oral cavity and oropharynx, radical radiation therapy. Data have been analyzed on 320 patients in this interim report. In the supraglottic larynx group local-regional control is significantly better for surgery and postoperative radiation therapy. The treatment differences in local-regional control in the oral cavity oropharynx and hypopharynx groups are statistically significant. No statistically significant treatment differences exist for survival in all sites or in any site; continued follow- up is necessary to make definite treatment comparisons. (authors)

  13. Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

    International Nuclear Information System (INIS)

    Qu, Xuanlu M.; Louie, Alexander V.; Ashman, Jonathan; Wasif, Nabil

    2017-01-01

    Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon of 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.

  14. Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Xuanlu M. [Department of Oncology, Queen' s University, Kingston, Ontario (Canada); Louie, Alexander V. [Department of Radiation Oncology, London Health Sciences Center, London, Ontario (Canada); Ashman, Jonathan [Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, Arizona (United States); Wasif, Nabil, E-mail: wasif.nabil@mayo.edu [Department of General Surgery, Mayo Clinic Arizona, Phoenix, Arizona (United States)

    2017-02-01

    Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon of 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.

  15. Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eng, Cathy [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez-Bigas, Miguel A.; Chang, George J.; Skibber, John M.; You, Y. Nancy [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Maru, Dipen M. [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Clemons, Marilyn V. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kopetz, Scott E.; Garrett, Christopher R.; Shureiqi, Imad [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-02-01

    Purpose: The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials: Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m{sup 2} to 825 mg/m{sup 2} orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions: The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

  16. The long term effect and outcome of preoperative chemotherapy combined with radiation therapy for bladder cancer

    International Nuclear Information System (INIS)

    Nasu, Takahito; Nakane, Hiroshi; Kamata, Seiji; Mitsui, Hiroshi; Hayashida, Shigeaki; Shinohara, Youichi.

    1996-01-01

    The object of this study is to evaluate the efficacy of preoperative chemotherapy combined with radiation therapy for bladder cancer. A total of 44 patients with bladder cancer were treated by preoperative chemotherapy combined with radiation therapy between October, 1981 and December, 1986. Clinical stages included 4 patients in Ta, 25 in T1, 11 in T2, and 4 in T3. Each patient was treated twice with 15 gray of radiation to the small pelvic cavity and a chemotherapy combination of adriamycin, cis-platinum, tegaful, and peplomycin. The average observation time after the therapy was 83 month, with the maximum being 146 months. Complete remission was included in 5 patients, partial remission in 27, and no change in 12. Thus, the overall effective rate was 72.8%. Operations, selected by the results of the preoperative therapy, included transurethral resection on 28 patients, transurethral fulguration on 2, partial cystectomy on 4, resection of tumor on 4, and total cystectomy on 3. Operations were not performed on 2 patients and not allowed on 1 patient. The outcome during the long-term follow-up included cancer related deaths in 4 patients, and death resulting from other disorders in 9. The 5-year survival rates for superficial and invasive bladder cancer were 92.4%, and 83.9%, respectively. The 10-year survival rates for superficial and invasive bladder cancer were also 92.4% and 83.9%, respectively. The 3-year and 5-year non-recurrence rates for superficial bladder cancer were 75.8%, and 66.9% respectively, according to the Kaplan-Meier method. On the other hand, the 3-year and 5-year non-recurrence rates for invasive bladder cancer were both 73.8%. During the follow-up between 9 and 11 years, 3 upper tract tumor were diagnosed (2 ureteral cancer, and 1 renal pelvic cancer). We concluded that preoperative chemotherapy combined with radiation therapy may be effective for the treatment of bladder cancer. (author)

  17. Comparing Active and Passive Distraction-Based Music Therapy Interventions on Preoperative Anxiety in Pediatric Patients and Their Caregivers.

    Science.gov (United States)

    Millett, Christopher R; Gooding, Lori F

    2018-01-13

    Young children who experience high levels of preoperative anxiety often exhibit distress behaviors, experience more surgical complications, and are at a higher risk for developing a variety of negative postoperative consequences. A significant factor in pediatric preoperative anxiety is the level of anxiety present in their caregivers. Active and passive music therapy interventions addressing anxiety prior to invasive procedures have been met with success. The purpose of this study was to investigate the comparative effectiveness of two distraction-based music therapy interventions on reducing preoperative anxiety in young pediatric surgical patients and their caregivers. A total of 40 pediatric patient and caregiver dyads undergoing ambulatory surgery were included in this study. Pediatric preoperative anxiety was measured pre- and post-intervention using the modified Yale Pediatric Anxiety Scale, while caregiver anxiety was measured through self-report using the short-form Strait-Trait Anxiety Inventory-Y6. Participants were randomized to either an active or passive intervention group for a preoperative music therapy session. Results indicated a significant reduction in preoperative anxiety for both patients and their caregivers regardless of intervention type. Neither active nor passive music therapy interventions were significantly more effective than the other. For future studies, the researchers recommend an increased sample size, controlling for various factors such as sedative premedication use, and testing interventions with patients in various stages of development. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  18. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    DEFF Research Database (Denmark)

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.

    2013-01-01

    estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...... of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect...... of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly...

  19. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    Energy Technology Data Exchange (ETDEWEB)

    Kordes, Sil [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Berge Henegouwen, Mark I. van [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Hulshof, Maarten C. [Department of Radiotherapy, Academic Medical Center, Amsterdam (Netherlands); Bergman, Jacques J.G.H.M. [Department of Gastroenterology, Academic Medical Center, Amsterdam (Netherlands); Vliet, Hans J. van der [Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam (Netherlands); Kapiteijn, Ellen [Department of Medical Oncology, Leiden University Medical Center, Leiden (Netherlands); Laarhoven, Hanneke W.M. van; Richel, Dick J. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Klinkenbijl, Jean H.G. [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Meijer, Sybren L. [Department of Pathology, Academic Medical Center, Amsterdam (Netherlands); Wilmink, Johanna W. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands)

    2014-09-01

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m{sup 2}) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.

  20. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    International Nuclear Information System (INIS)

    Kordes, Sil; Berge Henegouwen, Mark I. van; Hulshof, Maarten C.; Bergman, Jacques J.G.H.M.; Vliet, Hans J. van der; Kapiteijn, Ellen; Laarhoven, Hanneke W.M. van; Richel, Dick J.; Klinkenbijl, Jean H.G.; Meijer, Sybren L.; Wilmink, Johanna W.

    2014-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m 2 ) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%

  1. Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.

    Science.gov (United States)

    Nakao, Toshihiro; Iwata, Takashi; Hotchi, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Nishi, Masaaki; Takasu, Chie; Eto, Shohei; Teraoku, Hiroki; Shimada, Mitsuo

    2015-10-01

    Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non‑responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.

  2. Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates

    International Nuclear Information System (INIS)

    Malzoni, Carlos Eduardo

    1996-01-01

    The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author)

  3. Celecoxib sensitizes imatinib-resistant K562 cells to imatinib by inhibiting MRP1-5, ABCA2 and ABCG2 transporters via Wnt and Ras signaling pathways.

    Science.gov (United States)

    Dharmapuri, Gangappa; Doneti, Ravinder; Philip, Gundala Harold; Kalle, Arunasree M

    2015-07-01

    Imatinib mesylate, a tyrosine kinase inhibitor, is very effective in the treatment of chronic myeloid leukemia (CML). However, development of resistance to imatinib therapy is also a very common mechanism observed with long-term administration of the drug. Our previous studies have highlighted the role of cyclooxygenase-2 (COX-2) in regulating the expression of multidrug resistant protein-1 (MDR1), P-gp, in imatinib-resistant K562 cells (IR-K562) via PGE2-cAMP-PKC-NF-κB pathway and inhibition of COX-2 by celecoxib, a COX-2 specific inhibitor, inhibits this pathway and reverses the drug resistance. Studies have identified that not only MDR1 but other ATP-binding cassette transport proteins (ABC transporters) are involved in the development of imatinib resistance. Here, we tried to study the role of COX-2 in the regulation of other ABC transporters such as MRP1, MRP2, MRP3, ABCA2 and ABCG2 that have been already implicated in imatinib resistance development. The results of the study clearly indicated that overexpression of COX-2 lead to upregulation of MRP family proteins in IR-K562 cells and celecoxib down-regulated the ABC transporters through Wnt and MEK signaling pathways. The study signifies that celecoxib in combination with the imatinib can be a good alternate treatment strategy for the reversal of imatinib resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Appelt, Ane L.; Pløen, John; Vogelius, Ivan R.; Bentzen, Søren M.; Jakobsen, Anders

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D 50,i , and the normalized dose-response gradient, γ 50,i . Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D 50,TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), γ 50,TRG1 = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D 50,TRG1 and 2 = 72.1 Gy (CI 65.3-94.0 Gy), γ 50,TRG1 and 2 = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

  5. Imatinib en leucemia mieloide crónica Imatinib in chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Valia Pavón Morán

    2005-12-01

    Full Text Available La leucemia mieloide crónica (LMC fue la primera neoplasia en la que se pudo presentar un modelo de genotipo que sirviera de blanco a una terapia de acción molecular. La activación de múltiples vías de señales de transducción en las células con el gen BCR- ABL favorece el incremento de la proliferación celular, interfiere en la apoptosis y perturba la interacción con la matriz extracelular y el estroma. La introducción del Imatinib en el tratamiento de la LMC ha modificado la evolución y pronóstico de la enfermedad. Cuando se compara con los regímenes basados en interferón e hidroxiurea, el imatinib ha demostrado un alto nivel de eficacia asociado con un número menor de reacciones adversasChronic myeloid leukemia (CML was the first neoplasia in which it was possible to present a model of genotype that served as a target for a molecular action therapy. The activation of multiple ways of transduction signals in the cells with the BCR-ABL gene favors the increase of the cellular proliferation, interferes the apoptosis, and perturbs the interaction with the extracellular matrix and the stroma. The introduction of Imatinib in the treatment of CML has modified the evolution and prognosis of this disease. Imatinib has proved to have a high level of efficiency associated with a smaller number of adverse reactions on being compared with the regimens based on interferon and hydroxyurea

  6. Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer.

    Science.gov (United States)

    Myerson, Robert J; Tan, Benjamin; Hunt, Steven; Olsen, Jeffrey; Birnbaum, Elisa; Fleshman, James; Gao, Feng; Hall, Lannis; Kodner, Ira; Lockhart, A Craig; Mutch, Matthew; Naughton, Michael; Picus, Joel; Rigden, Caron; Safar, Bashar; Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea; Parikh, Parag

    2014-03-15

    Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT chemotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Effects of Tyrosine Kinase inhibitor Imatinib (Glivec) on PDGFR-positive primary and metastatic melanoma cells

    International Nuclear Information System (INIS)

    Straface, E.; Gambardella, L.; Vona, R.

    2009-01-01

    In summary these preliminary results indicate that Imatinib is able to induce apoptosis in metastatic cells and to sensitize these cells to pro-apoptotic agents commonly used in melanoma therapy, e.g. radiation or Cisplatin. Conversely, primary melanoma cells seem to be intrinsically resistant either to Imatinib given alone or in combination with Cisplatin or radiation. By contrast, these cells underwent autophagy and replicative senescence boostering their survival. Interestingly, the use of Imatinib in combination with anti-CD95/Fas antibodies sensitizes primary melanoma cells to apoptosis

  8. SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kotti, Angeliki, E-mail: angkotti@yahoo.gr; Holmqvist, Annica; Albertsson, Maria; Sun, Xiao-Feng, E-mail: xiao-feng.sun@liu.se

    2014-04-01

    Purpose: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT. Methods and Materials: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry. Results: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569). Conclusions: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  9. Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer.

    Science.gov (United States)

    Han, Kyung Su; Sohn, Dae Kyung; Kim, Dae Yong; Kim, Byung Chang; Hong, Chang Won; Chang, Hee Jin; Kim, Sun Young; Baek, Ji Yeon; Park, Sung Chan; Kim, Min Ju; Oh, Jae Hwan

    2016-04-01

    Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

  10. Impact of preoperative antithrombotic therapy on blood management after implantation of primary total knee arthroplasty.

    Science.gov (United States)

    Leitner, Lukas; Musser, Ewald; Kastner, Norbert; Friesenbichler, Jörg; Hirzberger, Daniela; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

    2016-08-04

    Red blood cell concentrates (RCC) substitution after total knee arthroplasty (TKA) is correlated with multifold of complications and an independent predictor for higher postoperative mortality. TKA is mainly performed in elderly patients with pre-existing polymorbidity, often requiring permanent preoperative antithrombotic therapy (PAT). The aim of this retrospective analysis was to investigate the impact of demand for PAT on inpatient blood management in patients undergoing TKA. In this study 200 patients were retrospectively evaluated after TKA for differences between PAT and non-PAT regarding demographic parameters, preoperative ASA score > 2, duration of operation, pre-, and intraoperative hemoglobin level, and postoperative parameters including amount of wound drainage, RCC requirement, and inpatient time. In a multivariate logistic regression analysis the independent influences of PAT, demographic parameters, ASA score > 2, and duration of the operation on RCC demand following TKA were analyzed. Patients with PAT were significantly older, more often had an ASA > 2 at surgery, needed a higher number of RCCs units and more frequently and had lower perioperative hemoglobin levels. Multivariate logistic regression revealed PAT was an independent predictor for RCC requirement. PAT patients are more likely to require RCC following TKA and should be accurately monitored with respect to postoperative blood loss.

  11. ART THERAPY MANAGEMENT IN THE PRE-OPERATIVE PERIOD IN PEDIATRICS

    Directory of Open Access Journals (Sweden)

    Ana Cláudia Afonso Valladares

    2004-04-01

    Full Text Available Every child, particularly those who will be submitted to surgery, needs to express themselves, createand establish relationships with the world. This study was based on qualitative studies which were, in turn,substantiated on the behavioral changes of patients and their images. It was developed in the pediatric clinic of apublic hospital in the city of Goiânia/GO in a two years’ period (1998-2000. The target population consisted ofhospitalized children in the pre-operative process. It was concluded that great therapeutic benefit was achievedfrom the use of art therapy for this population as it helped the children to recover their mental balance, thusstrengthening a healthier side of the child which had been deadened by the illness, hospitalization and treatment.

  12. Effect of preoperative chemotherapy and radiation therapy during and after radical operation for esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakamichi, Sonoko; Fujino, Yuji; Taenaka, Nobuyuki; Yoshiya, Ikuto; Murata, Atsuo [Osaka Univ., Suita (Japan). Hospital

    1997-10-01

    The effect of preoperative chemotherapy and radiation therapy (CR therapy) on peri- and postoperative circulatory and respiratory status was studied retrospectively. Forty-two patients of esophageal cancer who had radical operation were included in this study. Twelve patients had CR therapy before operation (group CR) and 30 patients without CR (group N). During the operation there was more bleeding in group CR than in group N, necessitating more intraoperative blood transfusion in group CR. Body weight of group CR increased more than that of group N from the 1st to the 4th postoperative day. AaDo{sub 2} also increased in group CR on the 1st postoperative day, which was thought to reflect an increase in water in the lungs. Diuretics required during the postoperative period did not show difference between both groups. Plasma IL-6 level was lower in group CR than in group N, although there was no statistical significance. No patients died in both groups. In conclusion, postoperative body weight and AaDo{sub 2} in group CR increased more than those in group N. (author)

  13. Associations between preoperative physical therapy and post-acute care utilization patterns and cost in total joint replacement.

    Science.gov (United States)

    Snow, Richard; Granata, Jaymes; Ruhil, Anirudh V S; Vogel, Karen; McShane, Michael; Wasielewski, Ray

    2014-10-01

    Health-care costs following acute hospital care have been identified as a major contributor to regional variation in Medicare spending. This study investigated the associations of preoperative physical therapy and post-acute care resource use and its effect on the total cost of care during primary hip or knee arthroplasty. Historical claims data were analyzed using the Centers for Medicare & Medicaid Services Limited Data Set files for Diagnosis Related Group 470. Analysis included descriptive statistics of patient demographic characteristics, comorbidities, procedures, and post-acute care utilization patterns, which included skilled nursing facility, home health agency, or inpatient rehabilitation facility, during the ninety-day period after a surgical hospitalization. To evaluate the associations, we used bivariate and multivariate techniques focused on post-acute care use and total episode-of-care costs. The Limited Data Set provided 4733 index hip or knee replacement cases for analysis within the thirty-nine-county Medicare hospital referral cluster. Post-acute care utilization was a significant variable in the total cost of care for the ninety-day episode. Overall, 77.0% of patients used post-acute care services after surgery. Post-acute care utilization decreased if preoperative physical therapy was used, with only 54.2% of the preoperative physical therapy cohort using post-acute care services. However, 79.7% of the non-preoperative physical therapy cohort used post-acute care services. After adjusting for demographic characteristics and comorbidities, the use of preoperative physical therapy was associated with a significant 29% reduction in post-acute care use, including an $871 reduction of episode payment driven largely by a reduction in payments for skilled nursing facility ($1093), home health agency ($527), and inpatient rehabilitation ($172). The use of preoperative physical therapy was associated with a 29% decrease in the use of any post-acute care

  14. Preoperative distraction in children: hand-held videogames vs clown therapy

    Directory of Open Access Journals (Sweden)

    M. Messina

    2014-12-01

    Full Text Available Anxiety in children undergoing surgery is characterized by feelings of tension, apprehension, nervousness and fear which may manifest differently. Postoperative behavioural changes such as nocturnal enuresis, feeding disorders, apathy, and sleep disturbances may stem from postoperative anxiety. Some Authors pointed out that over 60% of children undergoing surgery are prone to developing behavioural alterations 2 weeks after surgery. Variables such as age, temperament and anxiety both in children and parents are considered predictors of such changes.1 Studies were published describing how psycho-behavioural interventions based on play, learning and entertainment in preparing children for surgery, may reduce preoperative anxiety. Clown-therapy is applied in the most important paediatric facilities and has proved to diminish children’s emotional distress and sufferance, as well as consumption of both analgesics and sedatives and to facilitate the achievement of therapeutic goals. The aim of our study was to evaluate the efficacy of clown-therapy during the child’s hospital stay, with a view to optimizing treatment and care, preventing behavioural alterations and enhancing the child’s overall life quality.

  15. Significance of endoscopic biopsy after preoperative irradiation therapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Takiguchi, Nobuhiro; Sarashina, Hiromi; Saito, Norio; Nunomura, Masao; Kohda, Keishi; Nakajima, Nobuyuki (Chiba Univ. (Japan). School of Medicine)

    1994-05-01

    To evaluate the utility of endoscopic biopsy before and after preoperative irradiation therapy for rectal cancer, we examined histologically both biopsy specimens and resected materials of forty-three patients. Two pieces of biopsy materials were taken both before and after irradiation therapy (total dose 42.6 Gy) from the marginal wall of the tumor, cavity and transitional mucosa, respectively. In biopsy specimens, according to the degree of degeneration of cancer cells, cases with remarkable changes of nucleus, nucleolus, and cytoplasm due to irradiation were classified into the severely degenerated group. According to the histological examinations of resected materials, twenty-four cases were under Grade 1b (Gr I), and nineteen cases were over Grade 2 (Gr II). The rates of cancer cells found in biopsy materials after irradiation were 91.7% in Gr I and were 47.4% in Gr II, respectively (p<0.01). Among the cases, 54.5% in Gr I and 100% in Gr II belonged to the severely degenerated group (p<0.05). Transitional mucosas were not greatly damaged by irradiation. As a result, the greater the irradiation effect was, the fewer cancer cells were found and the more degenerated cancer cells were found in biopsy specimens. But the rate of severely degenerated cells found in the biopsy specimens of little effect cases was high. So it was thought to be too difficult to predict the histological radiation effect of resected specimens from only biopsy specimens. (author).

  16. Preoperative distraction in children: hand-held videogames vs clown therapy.

    Science.gov (United States)

    Messina, M; Molinaro, F; Meucci, D; Angotti, R; Giuntini, L; Cerchia, E; Bulotta, A L; Brandigi, E

    2014-12-30

    Anxiety in children undergoing surgery is characterized by feelings of tension, apprehension, nervousness and fear which may manifest differently. Postoperative behavioural changes such as nocturnal enuresis, feeding disorders, apathy, and sleep disturbances may stem from postoperative anxiety. Some Authors pointed out that over 60% of children undergoing surgery are prone to developing behavioural alterations 2 weeks after surgery. Variables such as age, temperament and anxiety both in children and parents are considered predictors of such changes.1 Studies were published describing how psycho-behavioural interventions based on play, learning and entertainment in preparing children for surgery, may reduce preoperative anxiety. Clown-therapy is applied in the most important paediatric facilities and has proved to diminish children's emotional distress and sufferance, as well as consumption of both analgesics and sedatives and to facilitate the achievement of therapeutic goals. The aim of our study was to evaluate the efficacy of clown-therapy during the child's hospital stay, with a view to optimizing treatment and care, preventing behavioural alterations and enhancing the child's overall life quality.

  17. Acompanhamento farmacoterapêutico dos pacientes com leucemia mieloide crônica em uso de mesilato de imatinibe na Universidade Federal do Ceará The pharmacotherapeutic follow- up of patients with chronic myeloid leukemia (CML on imatinib mesylate therapy

    Directory of Open Access Journals (Sweden)

    Sterfen S. Aquino

    2009-01-01

    unregulated growth of myeloid precursor cells in the bone marrow. CML is associated with a characteristic chromosomal translocation known as the Philadelphia chromosome. This is a descriptive observational study of CML patients in the Walter Cantídio University Hospital, Federal University of Ceará, Brazil. The aim of the study was to investigate the efficacy and common side effects of imatinib mesylate therapy. Twenty- six patients were included in the study: 9 in the chronic phase (34.61%, 6 in the accelerated phase (23.08% and 11 in blast crises (42.31 %. The cases in the chronic phase had previous intolerance to interferon alpha (IFN- α. Complete hematological responses were observed in 7 patients: 5 in the chronic phase, 1 in the accelerated phase and 1 in blast crisis. During the first year of treatment, 4 patients in the chronic phase presented complete cytogenetic responses. One of these patients subsequently lost response. No patient in the accelerated phase or blast crisis showed complete cytogenetic response. Complete molecular response was confirmed in 1 patient in the chronic phase. Among the 18 patients who were alive at the end of the study, only 4 patients (22.22% had no complaint. The most commonly reported adverse events were: edema (50%, adynamia (33.33%, bone and / or joint pain (33.33%, headaches (27.78%, cramps (16,67%, diarrhea (16.67%, insomnia (16.67%, itching (16.67%, ecchymosis (11.11%, nauseas (11.11%, epigastric pain (5.55%, erythema (5.55%, shedding of tears (5.55%, dehydration of the skin and lips (5.55%, rush (5.55%, and sweating (5.55%. A minority of patients evolved with imatinib resistance. Newer drugs and trials are being developed to overcome resistance and to increase responsiveness to tyrosine- kinase inhibitors.

  18. [Use and Safety of Preoperative Oral Rehydration Therapy Using a Jelly Type Oral Rehydration Solution].

    Science.gov (United States)

    Yamada, Tomomi; Mukai, Nobuhiro; Tsuchida, Keiichirou; Hayashi, Kazuko

    2015-04-01

    Traditionally, perioperative nutritional management centered on fluid therapy, but in recent years, with the spread of enhanced recovery after surgery (ERAS) protocols, the utility of oral rehydration therapy (ORT) has been reported. There are few reports, however, on the safety of using jelly type oral rehydration solutions for ORT. We examined the effects of OS-1 jelly on gastric fluid and investigated its safety. A total of 147 patients (age range, 4-91 years), scheduled for elective surgery at our institution for whom ORT was indicated, were enrolled in this study. If the surgery was scheduled for the morning, patients were given two bottles of 200 g OS-1 jelly during the previous evening meal. If surgery was scheduled for the afternoon, two additional 200 g bottles were given to the patient with the morning meal on the day of surgery. Patients were allowed to drink water until two hours before the surgery. Gastric fluid was aspirated with a gastric tube after anesthesia induction, after which, volume and pH were measured. In all cases, gastric content was aspirated as a liquid, not a jelly. The volume and pH were 11.4 ± 14.6 ml and 2.8 ± 2.2, respectively. No major difference was seen in comparison with the data for OS-1 liquid. No postoperative aspiration pneumonia or reflux of gastric contents at the time of anesthesia induction was seen in any of the patients. From the present findings, if the time of water intake is strictly controlled, preoperative rehydration therapy using jelly-type oral rehydration solution is thought to be safe and comparable to liquid solution regarding its effects on gastric fluid.

  19. Synthesis and positron emission tomography studies of carbon-11-labeled imatinib (Gleevec)

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Kun-Eek [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Ding Yushin [Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Lin Kuoshyan [Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Alexoff, David [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Shea, Colleen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Xu Youwen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Muench, Lisa [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States)]. E-mail: fowler@bnl.gov

    2007-02-15

    Introduction: Imatinib mesylate (Gleevec) is a well known drug for treating chronic myeloid leukemia and gastrointestinal stromal tumors. Its active ingredient, imatinib ([4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridyl) -2-pyrimidinyl]amino]phenyl]benzamide), blocks the activity of several tyrosine kinases. Here we labeled imatinib with carbon-11 as a tool for determining the drug distribution and pharmacokinetics of imatinib, and we carried out positron emission tomography (PET) studies in baboons. Methods: [N-{sup 11}C-methyl]imatinib was synthesized from [{sup 11}C]methyl iodide and norimatinib was synthesized by the demethylation of imatinib (isolated from Gleevec tablets) according to a patent procedure [Collins JM, Klecker RW Jr, Anderson LW. Imaging of drug accumulation as a guide to antitumor therapy. US Patent 20030198594A1, 2003]. Norimatinib was also synthesized from the corresponding amine and acid. PET studies were carried out in three baboons to measure pharmacokinetics in the brain and peripheral organs and to determine the effect of a therapeutic dose of imatinib. Log D and plasma protein binding were also measured. Results: [N-{sup 11}C-methyl]imatinib uptake in the brain is negligible (consistent with P-glycoprotein-mediated efflux); it peaks and clears rapidly from the heart, lungs and spleen. Peak uptake and clearance occur more slowly in the liver and kidneys, followed by accumulation in the gallbladder and urinary bladder. Pretreatment with imatinib did not change uptake in the heart, lungs, kidneys and spleen, and increased uptake in the liver and gallbladder. Conclusions: [N-{sup 11}C-methyl]imatinib has potential for assessing the regional distribution and kinetics of imatinib in the human body to determine whether the drug targets tumors and to identify other organs to which the drug or its labeled metabolites distribute. Paired with tracers such as 2'deoxy-2'-[{sup 18}F]fluoro-D-glucose ({sup 18}FDG) and 3&apos

  20. Imatinib mesylate--gold standards and silver linings.

    Science.gov (United States)

    Peggs, K

    2004-09-01

    Imatinib mesylate represents the first of a new generation of molecularly targeted therapies engineered to disrupt signal transduction pathways. It is a tyrosine kinase inhibitor with relatively selective activity against the Abelson (ABL) proto-oncogene, platelet-derived growth factor receptor, and c-KIT receptor. Deregulated tyrosine kinase activity has been implicated as a central pathogenic event in a number of human malignancies, most notably chronic myeloid leukemia. In this myeloproliferative disorder the t(9;22) reciprocal translocation results in the generation of a novel fusion oncoprotein, BCR-ABL, with constitutive tyrosine kinase activity. Imatinib inhibits this activity, inducing remarkable rates of hematological and cytogenetic remission in excess of those seen with alternative medical therapies. Following a large phase III study comparing its efficacy with the combination of interferon alpha and low-dose cytarabine, it has emerged as the current gold standard therapy for patients with chronic-phase disease without a potential bone marrow donor and those considered unsuitable for bone marrow transplantation. Its integration into the management of those patients who might be considered for transplantation, which has historically been considered the only potentially curative approach, remains a major challenge. The increasing recognition and subsequent molecular characterization of resistance mechanisms has reinforced the need to exercise caution against deferring a proven curative therapy in favor of a treatment approach that is still investigational, with the spectre of increased numbers of patients progressing to sudden-onset blast crisis remaining the potential dark cloud in the silver lining for imatinib.

  1. Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

    1997-01-01

    Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

  2. Sphincter preservation in rectal cancer with preoperative radiation therapy and coloanal anastomosis: long term follow-up

    International Nuclear Information System (INIS)

    Wagman, Raquel; Minsky, Bruce D.; Cohen, Alfred M.; Guillem, Jose G.; Paty, Philip P.

    1998-01-01

    Background: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. Methods: Thirty six patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (5,T 2; 31,T 3 ) involving the distal half of the rectum and clinically required an abdominoperineal resection. The median tumor size was 3.8 cm [range: 1.5-7 cm] and the median distance from the anal verge was 4 cm [range: 3-7 cm]. The whole pelvis received 46.80 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 56 months [range: 4-121 months]. Results: Of the 35 patients who underwent resection, 5 (14%) had a complete pathologic response and 27 (77%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 5-year actuarial: 21%. The 5-year actuarial survival was 64%. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in the 27 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 85%. The median number of bowel movements/day was 2 (range: 0-8). Conclusions: Our data suggest that preoperative radiation therapy allows sphincter preservation in 77% of selected patients who would otherwise require an abdominoperineal resection, and 85% have good to excellent sphincter function. Given the moderate local failure rate, we now routinely use preoperative combined modality therapy plus postoperative chemotherapy for patients with clinical T 3 disease

  3. Five Fractions of Radiation Therapy Followed by 4 Cycles of FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

    International Nuclear Information System (INIS)

    Myerson, Robert J.; Tan, Benjamin; Hunt, Steven; Olsen, Jeffrey; Birnbaum, Elisa; Fleshman, James; Gao, Feng; Hall, Lannis; Kodner, Ira; Lockhart, A. Craig; Mutch, Matthew; Naughton, Michael; Picus, Joel; Rigden, Caron; Safar, Bashar; Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea; Parikh, Parag

    2014-01-01

    Background: Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results: 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87

  4. Five Fractions of Radiation Therapy Followed by 4 Cycles of FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Myerson, Robert J., E-mail: rmyerson@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Tan, Benjamin [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Hunt, Steven [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Olsen, Jeffrey [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Birnbaum, Elisa; Fleshman, James [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Gao, Feng [Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri (United States); Hall, Lannis [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Kodner, Ira [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Lockhart, A. Craig [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Mutch, Matthew [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Naughton, Michael; Picus, Joel; Rigden, Caron [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Safar, Bashar [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Parikh, Parag [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-03-15

    Background: Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. Methods and Materials: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. Results: 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87

  5. Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Michio [Minamata City Hospital and Medical Center, Minamata City, Kumamoto 867 (Japan); Kortylewicz, Zbigniew P.; Enke, Charles A.; Mack, Elizabeth; Baranowska-Kortylewicz, Janina, E-mail: jbaranow@unmc.edu [Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, NE 68198 (United States)

    2011-05-25

    Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy.

  6. Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

    International Nuclear Information System (INIS)

    Abe, Michio; Kortylewicz, Zbigniew P.; Enke, Charles A.; Mack, Elizabeth; Baranowska-Kortylewicz, Janina

    2011-01-01

    Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy

  7. Preoperative chemotherapy and radiation therapy for squamous cell carcinoma of the maxillary sinus

    International Nuclear Information System (INIS)

    Isobe, Koichi; Uno, Takashi; Hanazawa, Toyoyuki

    2005-01-01

    This study was undertaken to assess the prognostic factors for the management of squamous cell carcinoma (SCC) of the maxillary sinus, who received preoperative chemotherapy and radiation therapy (RT). We also elucidated the appropriate sequence of chemotherapy. A total of 124 patients (median age 62 years) with SCC of the maxillary sinus were analysed retrospectively. T3 or T4 disease was found in 93% of the patients. Thirty-nine patients received neoadjuvant chemotherapy (NA), 38 patients received concurrent chemoradiotherapy (CRT) and 47 patients received NA followed by CRT. The median dose of RT was 60 Gy. Maxillectomy was undertaken in 98 patients. The 5 year overall survival (OAS) and local control probability (LCP) were 56.6 and 73.7%, respectively. On univariate analysis, surgery (P<0.0001) and T classification (P<0.04) were significant prognostic factors for OAS and LCP. Histological grade and nodal status were also related to OAS. However, any chemotherapy sequence was not associated with the treatment outcome. On multivariate analysis, surgery (P<0.0005) and T classification (P<0.05) were identified as significant prognostic factors for LCP and OAS. This study suggests that both surgery and T stage are important prognostic factors for LCP and OAS in the management of SCC of the maxillary sinus. The appropriate sequence of chemotherapy remains to be elucidated in the future study. (author)

  8. Preoperative radiation therapy in regionally localized stage III non-small-cell lung carcinoma

    International Nuclear Information System (INIS)

    Reddy, S.; Faber, L.P.; Baumann, L.M.; Lee, M.S.; Jensik, R.J.; Kittle, C.F.; Bonomi, P.; Taylor, S.; Hendrickson, F.R.

    1988-01-01

    Seventy-four patients seen from January 1975 through December 1982 with clinical stage III M0 non-small-cell carcinoma of the lung were treated with a course of preoperative radiation therapy to be followed by surgical resection. Surgical resection was attempted 4 weeks later. All the patients except two were followed up for a minimum of 5 years or until death. Sixty-four patients (86%) had T3 tumors, while mediastinal nodal involvement was found in 41 (55%). The actuarial 5-year survival and disease-free survival rates for the entire group were 20% and 26%, respectively. Patients with a pathologically complete response had an actuarial disease-free survival rate of 50% at 5 years, compared with only 17% for those with gross residual disease at surgery. One-half of the patients with clinically uninvolved nodes were living disease free at 5 years, compared with only 20% of the patients with N2 disease. The patterns of failure are presented according to the histologic type and stage of the disease

  9. The Effects of Hyperbaric Oxygen Therapy on Experimental Colon Anastomosis After Preoperative Chemoradiotherapy

    Science.gov (United States)

    Yildiz, Ramazan; Can, Mehmet Fatih; Yagci, Gokhan; Ozgurtas, Taner; Guden, Metin; Gamsizkan, Mehmet; Ozturk, Erkan; Cetiner, Sadettin

    2013-01-01

    The aim of the present study was to investigate the effect of hyperbaric oxygen therapy (HBOT) on colon anastomosis after chemoradiotherapy (CRT). Sixty female Wistar-Albino rats were divided into 5 groups and underwent left colon resection and end-to-end anastomosis. CRT simulation was performed on 2 sham groups before the anastomosis, and 1 of these groups was administered additional postoperative HBOT. Two groups were administered CRT before the anastomosis, and 1 of them received additional postoperative HBOT. On postoperative day 5, all groups underwent relaparotomy; burst pressure was measured and samples were obtained for histopathologic and biochemical analysis. There was a significant weight loss in the CRT groups and postoperative HBOT had an improving effect. Significantly decreased burst pressure values increased up to the levels of the controls after HBOT. Hydroxyproline levels were elevated in all groups compared to the control group. Hydroxyproline levels decreased with HBOT after CRT. No significant difference was observed between the groups regarding fibrosis formation at the anastomosis site. However, regression was observed in fibrosis in the group receiving HBOT after CRT. Preoperative CRT affected anastomosis and wound healing unfavorably. These unfavorable effects were alleviated by postoperative HBOT. HBOT improved the mechanical and biochemical parameters of colon anastomosis in rats. PMID:23438274

  10. Medical impulsive therapy (MIT): the impact of 1 week of preoperative tamsulosin on deployment of 16-French ureteral access sheaths without preoperative ureteral stent placement.

    Science.gov (United States)

    Kaler, Kamaljot S; Safiullah, Shoaib; Lama, Daniel J; Parkhomenko, Egor; Okhunov, Zhamshid; Ko, Young H; Huynh, Linda; Patel, Roshan M; Landman, Jaime; Clayman, Ralph V

    2018-05-25

    Medical expulsive therapy is based on pharmacologic ureteral relaxation. We hypothesized this concept may facilitate the deployment of the large 16 French (F) ureteral access sheath (UAS) when patients are intentionally pre-treated with oral tamsulosin, i.e., medical impulsive therapy. We retrospectively analyzed our experience with UAS deployment during endoscopic-guided percutaneous nephrolithotomy in prone position in patients pre-treated for 1 week with oral tamsulosin with a contemporary untreated cohort. Between January 2015 and September 2016, seventy-seven patients without a pre-existing ureteral stent met inclusion criteria. Demographic data, tamsulosin usage, UAS size, deployment failure, ureteral injuries, stone-free rates, and complications were recorded. Univariate and multivariate analysis was conducted to assess the impact of tamsulosin on deployment of the 16F UAS. There was no statistical difference between the tamsulosin (n = 40) group and non-tamsulosin (n = 37) group in regard to demographic data. The tamsulosin group had a significantly higher percentage of 16F UAS deployment, 87 vs. 43% (p < 0.001), and no significant difference in ureteral injuries (p = 0.228). Univariate and multivariate analysis revealed that tamsulosin significantly increased the odds ratio (9.3 and 19.4, respectively) for successful passage of a 16F UAS. Despite a larger stone volume, there was no significant difference in computed tomography scan complete stone-free rates (29 vs. 42%; p = 0.277) at median post-operative time of only 3 days. In this retrospective study, 1 week of preoperative tamsulosin was associated with an increase in the deployment of a 16F UAS in patients without preoperative ureteral stent placement.

  11. Concurrent Male Gynecomastia and Testicular Hydrocele after Imatinib Mesylate Treatment of a Gastrointestinal Stromal Tumor

    Science.gov (United States)

    Kim, Hawk; Chang, Heung-Moon; Ryu, Min-Hee; Kim, Tae-Won; Sohn, Hee-Jung; Kim, So-Eun; Kang, Hye-Jin; Park, Sarah; Lee, Jung-Shin

    2005-01-01

    We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male patient presented for management of hepatic masses. Two years earlier, he had undergone a small bowel resection to remove an intraabdominal mass later shown to be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan revealed multiple hepatic masses, which were compatible with metastatic GIST, and he was prescribed imatinib 400 mg/day. During treatment, he experienced painful enlargement of the left breast and scrotal swelling. Three months after cessation of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he experienced painful enlargement of the right breast and scrotal swelling. He was diagnosed with male gynecomastia caused by decreased testosterone and non-communicative testicular hydrocele. He was given androgen support and a hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. This is the first report, to our knowledge, describing concurrent male gynecomastia and testicular hydrocele after imatinib treatment of a patient with GIST. PMID:15953881

  12. Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Vidal-Petiot, Emmanuelle; Rea, Delphine; Serrano, Fidéline; Stehlé, Thomas; Gardin, Claude; Rousselot, Philippe; Peraldi, Marie-Noëlle; Flamant, Martin

    2016-03-01

    Monitoring renal function is important in imatinib-treated patients with chronic myeloid leukemia because serum creatinine may increase during the course of therapy. The mechanism of this increase and its reversibility on treatment cessation have never been investigated. We retrospectively analyzed data from imatinib-treated patients explored in our renal physiology unit with measurement of glomerular filtration rate (urinary clearance of (51)CrEDTA) and of urinary clearance and tubular secretion of creatinine. Results were compared with those of controls matched for measured glomerular filtration rate, age, gender, and ethnicity. We also analyzed variations of serum creatinine before and during imatinib cessation and after imatinib resumption in patients enrolled in imatinib discontinuation studies. In 4 imatinib-treated patients who underwent thorough renal exploration, the part of creatinine clearance due to tubular secretion was negligible (2.4, 3.1, -1.3, and 2.8 mL/min) and significantly lower than that measured in their respective controls (17.7 ± 5.6, 43.0 ± 18.0, 23.1 ± 6.7, and 18.6 ± 5.6 mL/min, P creatinine tubular secretion (20.3 vs. 17.9 ± 5.2 mL/min in the control population, P = .2). In 15 patients of imatinib discontinuation studies, a median decrease in serum creatinine of 17.9% was observed after imatinib cessation. Resumption of treatment in 6 patients led to a median increase in serum creatinine of 18.8%. Imatinib completely blunts tubular secretion of creatinine, a previously unreported pharmacologic property. This inhibition increases serum creatinine independently of any glomerular dysfunction and is fully reversible on imatinib cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. One year results of preoperative single bolus ATG-Fresenius induction therapy in sensitized renal transplant recipients.

    Science.gov (United States)

    Wang, D; Chen, J H; Wu, W Z; Yang, S L; Wu, G J; Wang, H; Tan, J M

    2007-01-01

    Sensitization in kidney transplantation is associated with more acute rejections, inferior graft survival, and an increase in delayed graft function. This study was designed to evaluate the efficacy and safety of preoperative single bolus antithymocyte globulin (ATG) induction therapy in sensitized renal transplant recipients. Fifty-six cadaveric donor kidney transplant recipients were divided into two groups: Group I (nonsensitized group, n = 30) and group II (sensitized group, PRA>10%, n = 26). ATG was given as a single preoperative bolus induction therapy to group II (ATG IV; 9 mg/kg). The group I patients were treated with mycophenolate mofetil preoperatively as induction therapy. The basic immunosuppressive regimen included tacrolimus (FK-506) or cyclosporine, mycophenolate mofetil, and prednisolone. After hospital discharge, patients were followed on a routine outpatient basis for 12 months. Acute rejection episodes (ARE) occurred in 20% (6/30) of group I and 15.38% (4/26) of group II patients (P = NS). Infections occurred in eight patients (26.7%) as 11 episodes (36.7%), averaging 1.4 episodes per infected patient in group 1, and 6 patients (23.1%) for a total of 10 episodes (38.5%), averaging 1.7 episodes per infected patient, in group II (P = NS). Occurrence of side effects and hospital stay were almost comparable in the two groups. No delayed graft function was observed in either group. The 12-month actuarial patient and graft survival were 100% in Group I and II. A preoperative single bolus ATG induction therapy was an effective and safe therapeutic measure, yielding an acceptable acute rejection rate in presensitized renal transplant recipients.

  14. Phase I study of imatinib, cisplatin and 5-fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma

    International Nuclear Information System (INIS)

    Mayr, Martina; Becker, Karen; Schulte, Nadine; Belle, Sebastian; Hofheinz, Ralf; Krause, Annekatrin; Schmid, Roland M; Röcken, Christoph; Ebert, Matthias P

    2012-01-01

    Despite all benefit provided by established therapies prognosis of gastric cancer remains poor. Targeted inhibition of platelet derived growth factor receptor (PDGFR) by imatinib may influence tumor growth and amplify chemotherapeutic effects. This phase I study evaluated dose limiting toxicity (DLT) of imatinib combinated with chemotherapy according to a 3-patient cohort dose-escalating design. Thirty-five patients received cisplatin (60 mg/m 2 d1 q 3w)/ capecitabine (1250 mg/m 2 bid d1-14 q 21) or cisplatin (50 mg/m 2 d1 q 2w)/ 5-fluoruracil (2 g/m 2 d1, q 1w). Imatinib was started d - 4 with dose escalation from 300 to 700 mg QD in 100 mg steps. At imatinib dose level 1 (300mg) one DLT was observed, three more patients were enrolled without further DLT. At dose level 5 (700 mg) two gastric perforations occurred, so 600 mg imatinib emerged as the maximum tolerated dose. Major grade 3/4 toxicities were nausea (6%), anemia (6%) and fatigue (3%). Response evaluation revealed partial response in 27% and stable disease in 43% of the assessable patients. Combination of imatinib and chemotherapy is well tolerated. Response rates were not superior to those of standard therapy. Further investigations of a larger group of patients are required to confirm the amplification of chemotherapy effects by imatinib. European Clinical Trials Database: Eudra-CT2006-005792-17 and Clinical Trials Database: NCT00601510

  15. Intensity modulated radiation-therapy for preoperative posterior abdominal wall irradiation of retroperitoneal liposarcomas

    International Nuclear Information System (INIS)

    Bossi, Alberto; De Wever, Ivo; Van Limbergen, Erik; Vanstraelen, Bianca

    2007-01-01

    Purpose: Preoperative external-beam radiation therapy (preop RT) in the management of Retroperitoneal Liposarcomas (RPLS) typically involves the delivery of radiation to the entire tumor mass: yet this may not be necessary. The purpose of this study is to evaluate a new strategy of preop RT for RPLS in which the target volume is limited to the contact area between the tumoral mass and the posterior abdominal wall. Methods and Materials: Between June 2000 and Jan 2005, 18 patients with the diagnosis of RPLS have been treated following a pilot protocol of pre-op RT, 50 Gy in 25 fractions of 2 Gy/day. The Clinical Target Volume (CTV) has been limited to the posterior abdominal wall, region at higher risk for local relapse. A Three-Dimensional conformal (3D-CRT) and an Intensity Modulated (IMRT) plan were generated and compared; toxicity was reported following the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0. Results: All patients completed the planned treatment and the acute toxicity was tolerable: 2 patients experienced Grade 3 and 1 Grade 2 anorexia while 2 patients developed Grade 2 nausea. IMRT allows a better sparing of the ipsilateral and the contralateral kidney. All tumors were successfully resected without major complications. At a median follow-up of 27 months 2 patients developed a local relapse and 1 lung metastasis. Conclusions: Our strategy of preop RT is feasible and well tolerated: the rate of resectability is not compromised by limiting the preop CTV to the posterior abdominal wall and a better critical-structures sparing is obtained with IMRT

  16. Avoiding preoperative breast MRI when conventional imaging is sufficient to stage patients eligible for breast conserving therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pengel, Kenneth E., E-mail: k.pengel@nki.nl [Department of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Loo, Claudette E. [Department of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Wesseling, Jelle [Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Pijnappel, Ruud M. [Department of Radiology/Image Sciences Institute, University Medical Center Utrecht Heidelberglaan 100, 3584 CX Utrecht (Netherlands); Rutgers, Emiel J.Th. [Department of Surgical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Gilhuijs, Kenneth G.A. [Department of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Department of Radiology/Image Sciences Institute, University Medical Center Utrecht Heidelberglaan 100, 3584 CX Utrecht (Netherlands)

    2014-02-15

    Aim: To determine when preoperative breast MRI will not be more informative than available breast imaging and can be omitted in patients eligible for breast conserving therapy (BCT). Methods: We performed an MRI in 685 consecutive patients with 692 invasive breast tumors and eligible for BCT based on conventional imaging and clinical examination. We explored associations between patient, tumor, and conventional imaging characteristics and similarity with MRI findings. Receiver operating characteristic (ROC) analysis was employed to compute the area under the curve (AUC). Results: MRI and conventional breast imaging were similar in 585 of the 692 tumors (85%). At univariate analysis, age (p < 0.001), negative preoperative lymph node status (p = 0.011), comparable tumor diameter at mammography and at ultrasound (p = 0.001), negative HER2 status (p = 0.044), and absence of invasive lobular cancer (p = 0.005) were significantly associated with this similarity. At multivariate analysis, these factors, except HER2 status, retained significant associations. The AUC was 0.68. Conclusions: It is feasible to identify a subgroup of patients prior to preoperative breast MRI, who will most likely show similar results on conventional imaging as on MRI. These findings enable formulation of a practical consensus guideline to determine in which patients a preoperative breast MRI can be omitted.

  17. Avoiding preoperative breast MRI when conventional imaging is sufficient to stage patients eligible for breast conserving therapy

    International Nuclear Information System (INIS)

    Pengel, Kenneth E.; Loo, Claudette E.; Wesseling, Jelle; Pijnappel, Ruud M.; Rutgers, Emiel J.Th.; Gilhuijs, Kenneth G.A.

    2014-01-01

    Aim: To determine when preoperative breast MRI will not be more informative than available breast imaging and can be omitted in patients eligible for breast conserving therapy (BCT). Methods: We performed an MRI in 685 consecutive patients with 692 invasive breast tumors and eligible for BCT based on conventional imaging and clinical examination. We explored associations between patient, tumor, and conventional imaging characteristics and similarity with MRI findings. Receiver operating characteristic (ROC) analysis was employed to compute the area under the curve (AUC). Results: MRI and conventional breast imaging were similar in 585 of the 692 tumors (85%). At univariate analysis, age (p < 0.001), negative preoperative lymph node status (p = 0.011), comparable tumor diameter at mammography and at ultrasound (p = 0.001), negative HER2 status (p = 0.044), and absence of invasive lobular cancer (p = 0.005) were significantly associated with this similarity. At multivariate analysis, these factors, except HER2 status, retained significant associations. The AUC was 0.68. Conclusions: It is feasible to identify a subgroup of patients prior to preoperative breast MRI, who will most likely show similar results on conventional imaging as on MRI. These findings enable formulation of a practical consensus guideline to determine in which patients a preoperative breast MRI can be omitted

  18. Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

    International Nuclear Information System (INIS)

    Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J.

    1993-01-01

    The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs

  19. A comparison of laparoscopic and open surgery following pre-operative chemoradiation therapy for locally advanced lower rectal cancer

    International Nuclear Information System (INIS)

    Kusano, Toru; Inomata, Masafumi; Hiratsuka, Takahiro

    2014-01-01

    Although pre-operative chemoradiation therapy for advanced lower rectal cancer is a controversial treatment modality, it is increasingly used in combination with surgery. Few studies have considered the combination of chemoradiation therapy followed by laparoscopic surgery for locally advanced lower rectal cancer; therefore, this study aimed to assess the usefulness of this therapeutic combination. We retrospectively reviewed the medical records of patients with locally advanced lower rectal cancer treated by pre-operative chemoradiation therapy and surgery from February 2002 to November 2012 at Oita University. We divided patients into an open surgery group and a laparoscopic surgery group and evaluated various parameters by univariate and multivariate analyses. In total, 33 patients were enrolled (open surgery group, n=14; laparoscopic surgery group, n=19). Univariate analysis revealed that compared with the open surgery group, operative time was significantly longer, whereas intra-operative blood loss and intra-operative blood transfusion requirements were significantly less in the laparoscopic surgery group. There were no significant differences in post-operative complication and recurrence rates between the two groups. According to multivariate analysis, operative time and intra-operative blood loss were significant predictors of outcome in the laparoscopic surgery group. This study suggests that laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is a safe procedure. Further prospective investigation of the long-term oncological outcomes of laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is required to confirm the advantages of laparoscopic surgery over open surgery. (author)

  20. Downregulation of miR-451 in Tunisian chronic myeloid leukemia patients: potential implication in imatinib resistance.

    Science.gov (United States)

    Soltani, Ismael; Douzi, Kais; Gharbi, Hanen; Benhassine, Islem; Teber, Mouheb; Amouri, Hassiba; Ben Hadj Othman, Hind; Farrah, Ahlem; Ben Lakhel, Raihane; Abbes, Salem; Menif, Samia

    2017-05-01

    Resistance to imatinib has been recognized as a major challenge for the treatment of chronic myeloid leukemia (CML). Aberrant expression of miR-451 has been reported to participate in anticancer drug resistance. However, the role of miR-451 in imatinib resistance has not been investigated. The present study was undertaken to determine the expression of miR-451 in order to find a possible association between the expression of this miRNA and imatinib resistance in Tunisian CML patients. First, real-time RT-PCR was performed to identify the expression of miR-451 in peripheral leukocytes of 59 CML patients treated with imatinib. Then, bioinformatics analysis was carried out to understand the regulatory roles of miR-451 in imatinib-resistant process. Downregulated miR-451 was observed in imatinib-resistant CML cases. In silico analysis identified MYC as a potential target of miR-451. We further revealed the existence of an MYC-binding site in MiR-451 promoter region. On the other hand, increased level of MYC was detected in imatinib-resistant CML cases which may explain the causative role of MYC in CML cases and the downregulation of miR-451. Taken together, our findings suggest that miR-451 and MYC form together a regulatory loop which may act as a potential therapeutic target, and disruption of suggested regulatory loop could help to improve CML therapy.

  1. LAM Pilot Study with Imatinib Mesylate (LAMP-1)

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0132 TITLE: LAM Pilot Study with Imatinib Mesylate (LAMP-1) PRINCIPAL INVESTIGATOR: Charlie Strange, MD...regarding imatinib mesylate (imatinib) in the treatment of Lymphangioleiomyomatosis ( LAM ) sufficient to power and design a phase 3 imatinib vs. placebo...clinical trial. The hypothesis is that imatinib will be equivalent to rapamycin in short term efficacy and safety. Currently, most LAM patients are

  2. Successful combination treatment of a patient with progressive juvenile localized scleroderma (morphea) using imatinib, corticosteroids, and methotrexate.

    Science.gov (United States)

    Inamo, Yasuji; Ochiai, Toyoko

    2013-01-01

    We report a case of progressive juvenile localized scleroderma (JLS or morphea) treated with a combination of imatinib, corticosteroids, and methotrexate. This therapy halted the progressive skin thickening and the hand and finger joint deformity in the early stages of the disease. We conclude that imatinib used in addition to standard treatment with systemic corticosteroids and methotrexate may be of therapeutic benefit for individuals with JLS. © 2012 Wiley Periodicals, Inc.

  3. Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease.

    Science.gov (United States)

    Waterman, Matti; Xu, Wei; Dinani, Amreen; Steinhart, A Hillary; Croitoru, Kenneth; Nguyen, Geoffrey C; McLeod, Robin S; Greenberg, Gordon R; Cohen, Zane; Silverberg, Mark S

    2013-03-01

    Previous investigations of short-term outcomes after preoperative exposure to biological therapy in inflammatory bowel disease (IBD) were conflicting. The authors aimed to assess postoperative outcomes in patients who underwent abdominal surgery with recent exposure to anti-tumour necrosis factor therapy. A retrospective case-control study with detailed matching was performed for subjects with IBD with and without exposure to biologics within 180 days of abdominal surgery. Postoperative outcomes were compared between the groups. 473 procedures were reviewed consisting of 195 patients with exposure to biologics and 278 matched controls. There were no significant differences in most postoperative outcomes such as: length of stay, fever (≥ 38.5°C), urinary tract infection, pneumonia, bacteraemia, readmission, reoperations and mortality. On univariate analysis, procedures on biologics had more wound infections compared with controls (19% vs 11%; p=0.008), but this was not significant in multivariate analysis. Concomitant therapy with biologics and thiopurines was associated with increased frequencies of urinary tract infections (p=0.0007) and wound infections (p=0.0045). Operations performed ≤ 14 days from last biologic dose had similar rates of infections and other outcomes when compared with those performed within 15-30 days or 31-180 days. Patients with detectable preoperative infliximab levels had similar rates of wound infection compared with those with undetectable levels (3/10 vs 0/9; p=0.21). Preoperative treatment with TNF-α antagonists in patients with IBD is not associated with most early postoperative complications. A shorter time interval from last biological dose is not associated with increased postoperative complications. In most cases, surgery should not be delayed, and appropriate biological therapy may be continued perioperatively.

  4. Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

    Directory of Open Access Journals (Sweden)

    Fiorentini Giammaria

    2006-01-01

    Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

  5. Cumulative clinical experience from a decade of use: imatinib as first-line treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Baran Y

    2012-11-01

    Full Text Available Yusuf Baran,1 Guray Saydam21Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey; 2Department of Hematology, School of Medicine, Ege University, Izmir, TurkeyAbstract: Chronic myeloid leukemia (CML is a malignant disease that originates in the bone marrow and is designated by the presence of the Philadelphia (Ph+ chromosome, a translocation between chromosomes 9 and 22. Targeted therapy against CML commenced with the development of small-molecule tyrosine kinase inhibitors (TKIs exerting their effect against the oncogenic breakpoint cluster region (BCR-ABL fusion protein. Imatinib emerged as the first successful example of a TKI used for the treatment of chronic-phase CML patients and resulted in significant improvements in response rate and overall survival compared with previous treatments. However, a significant portion of patients failed to respond to the therapy and developed resistance against imatinib. Second-generation TKIs nilotinib and dasatinib were to have higher efficiency in clinical trials in imatinib- resistant or intolerant CML patients compared with imatinib. Identification of novel strategies such as dose escalation, drug combination therapy, and use of novel BCR-ABL inhibitors may eventually overcome resistance against BCR-ABL TKIs. This article reviews the history of CML, including the treatment strategies used prediscovery of TKIs and the preclinical and clinical data obtained after the use of imatinib, and the second-generation TKIs developed for the treatment of CML.Keywords: drug resistance, tyrosine kinase inhibitors, chronic myeloid leukemia, imatinib, BCR/ABL

  6. Preoperative low level laser therapy in dogs undergoing tibial plateau levelling osteotomy: A blinded, prospective, randomized clinical trial.

    Science.gov (United States)

    Rogatko, Cleo P; Baltzer, Wendy I; Tennant, Rachel

    2017-01-16

    To evaluate the influence of preoperative low-level laser therapy (LLLT) on therapeutic outcomes of dogs undergoing tibial plateau levelling osteotomy (TPLO). Healthy dogs undergoing TPLO were randomly assigned to receive either a single preoperative LLLT treatment (800-900 nm dual wavelength, 6 W, 3.5 J/cm 2 , 100 cm 2 area) or a sham treatment. Lameness assessment and response to manipulation, as well as force plate analysis, were performed preoperatively, then again at 24 hours, two weeks, and eight weeks postoperatively. Radiographic signs of healing of the osteo-tomy were assessed at eight weeks postoperatively. Twenty-seven dogs (27 stifles) were included and no major complications occurred. At eight weeks postoperatively, a significant difference in peak vertical force analysis was noted between the LLLT (39.6% ± 4.7%) and sham groups (28.9% ± 2.6%), (p dogs in the LLLT group (6.6 ± 1.6 years) was greater than that for the sham group (4.5 ± 2.0, p dogs (5/8) had healed at the eight-week time point than in the sham group (3/12) despite the age difference (p = 0.11) Clinical significance: The results of this study demonstrate that improved peak vertical force could be related to the preoperative use of LLLT for dogs undergoing TPLO at eight weeks postoperatively. The use of LLLT may improve postoperative return to function following canine osteotomies and its use is recommended.

  7. Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    International Nuclear Information System (INIS)

    Kim, Jin C.; Ha, Ye J.; Roh, Seon A.; Cho, Dong H.; Choi, Eun Y.; Kim, Tae W.; Kim, Jong H.; Kang, Tae W.; Kim, Seon Y.; Kim, Yong S.

    2013-01-01

    Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. Methods and Materials: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. Results: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). Conclusion: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts

  8. Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

    Directory of Open Access Journals (Sweden)

    Waring Paul

    2004-10-01

    Full Text Available Abstract Background The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. Case presentation A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression

  9. Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

    International Nuclear Information System (INIS)

    Hughes, Brett; Yip, Desmond; Goldstein, David; Waring, Paul; Beshay, Victoria; Chong, Guan

    2004-01-01

    The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred. This case illustrates that the brain can be a

  10. Imatinib Intolerance Is Associated With Blastic Phase Development in Philadelphia Chromosome-Positive Chronic Myeloid Leukemia.

    Science.gov (United States)

    Ángeles-Velázquez, Jorge Luis; Hurtado-Monroy, Rafael; Vargas-Viveros, Pablo; Carrillo-Muñoz, Silvia; Candelaria-Hernández, Myrna

    2016-08-01

    Over the past years, the survival of patients with Philadelphia-positive chronic myeloid leukemia (CML Ph(+)) has increased as a result of therapy with tyrosin kinase inhibitors (TKIs). Intolerance to TKIs has been described in approximately 20% of patients receiving treatment. We studied the incidence of imatinib intolerance in patients with CML Ph(+) and their outcome in our CML reference site, as there is no information about the evolution of patients intolerant to TKIs. A group of 86 patients with CML Ph(+) receiving imatinib monotherapy who abandoned treatment were the basis for this study. We present the trends of their disease evolution. The median of age at diagnosis was 42 years. Within a year, 19 (22%) of 86 patients developed imatinib intolerance, all of them with grade III or IV disease that required imatinib dose reduction or discontinuation. Of these patients, 16 (84%) of 19 developed transformation to blastic phase. The cumulative incidences of blastic phase development were 47% in the nonintolerant group and 84% in the intolerant group. There was a relative risk for those with imatinib intolerance to develop blastic phase of 1.78 (95% confidence interval, 1.28 to 2.42) (P treatment is available. Future research should to determine whether the origin of this evolution is really due to the intolerance itself or whether it is due to a more aggressive form of the disease, perhaps related to genetic transformation. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Impact of imatinib interruption and duration of prior hydroxyurea on the treatment outcome in patients with chronic myeloid leukemia: Single institution experience.

    Science.gov (United States)

    Edesa, Wael Abdelgawad; Abdel-malek, Raafat Ragaey

    2015-06-01

    Optimal response requires that patients should be maintained on the drug continuously. To evaluate the influence of imatinib interruption and prior hydroxyurea use on the outcome of patients with chronic myeloid leukemia. Between January 2010 and November 2013, patients with chronic phase who received imatinib at the Kasr Al-ainy Center of Clinical Oncology were included. Sixty patients were included in this study, thirty three patients (55%) received imatinib upfront, while 27 (45%) received imatinib post hydroxyurea. Imatinib was not given regularly in 50% of patients. In terms of response, only major molecular response and complete molecular response were statistically significant in favor of patients who were receiving imatinib regularly compared to those who had interruption (phydroxyurea. The median progression free survival was 30.3 months (95% CI 24.3-36.3). Among the group of patients who received imatinib regularly, progression free survival was longer (p=0.049), there was no difference between those who received prior hydroxyurea versus those who did not (p=0.67). Duration of prior hydroxyurea had no impact on response or progression free survival, while patients regular on imatinib had statistically significant difference with respect to major molecular response, complete molecular response and progression free survival compared to those who had periods of drug interruption, thus we need more governmental support to supply the drug without interruption to improve the outcome of therapy. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  12. Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    Deenik, Wendy; Janssen, Jeroen J. W. M.; van der Holt, Bronno; Verhoef, Gregor E. G.; Smit, Willem M.; Kersten, Marie José; Daenen, Simon M. G. J.; Verdonck, Leo F.; Ferrant, Augustin; Schattenberg, Anton V. M. B.; Sonneveld, Pieter; van Marwijk Kooy, Marinus; Wittebol, Shulamit; Willemze, Roelof; Wijermans, Pierre W.; Beverloo, H. Berna; Löwenberg, Bob; Valk, Peter J. M.; Ossenkoppele, Gert J.; Cornelissen, Jan J.

    2010-01-01

    In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study. Having reported feasibility previously, we hereby

  13. Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    Deenik, W.; Janssen, J.J.W.M.; van der Holt, B.; Verhoef, G.E.G.; Smit, W.M.; Kersten, M.J.; Daenen, S.M.G.J.; Verdouck, L.F.; Ferrant, A.; Schattenberg, A.V.M.B.; Sonneveld, P.; Kooy, M.V.M.; Wittebol, S.; Willemze, R.; Wijermans, P.W.; Beverloo, H.B.; Lowenberg, B.; Valk, P.J.M.; Ossenkoppele, G.J.; Cornelissen, J.J.

    2010-01-01

    Background In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study. Design and Methods Having reported

  14. Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    Deenik, Wendy; Janssen, Jeroen J. W. M.; van der Holt, Bronno; Verhoef, Gregor E. G.; Smit, Willem M.; Kersten, Marie Jose; Daenen, Simon M. G. J.; Verdouck, Leo F.; Ferrant, Augustin; Schattenberg, Anton V. M. B.; Sonneveld, Pieter; Kooy, Marinus van Marwijk; Wittebol, Shulamit; Willemze, Roelof; Wijermans, Pierre W.; Beverloo, H. Berna; Lowenberg, Bob; Valk, Peter J. M.; Ossenkoppele, Gert J.; Cornelissen, Jan J.

    Background In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study. Design and Methods Having reported

  15. Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

    International Nuclear Information System (INIS)

    Horton, Janet K.; Blitzblau, Rachel C.; Yoo, Sua; Geradts, Joseph; Chang, Zheng; Baker, Jay A.; Georgiade, Gregory S.; Chen, Wei; Siamakpour-Reihani, Sharareh; Wang, Chunhao; Broadwater, Gloria; Groth, Jeff; Palta, Manisha; Dewhirst, Mark; Barry, William T.; Duffy, Eileen A.

    2015-01-01

    Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should

  16. Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Horton, Janet K., E-mail: janet.horton@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Blitzblau, Rachel C.; Yoo, Sua [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Geradts, Joseph [Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Chang, Zheng [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Baker, Jay A. [Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Georgiade, Gregory S. [Department of Surgery, Duke University Medical Center, Durham, North Carolina (United States); Chen, Wei [Department of Bioinformatics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Siamakpour-Reihani, Sharareh; Wang, Chunhao [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Broadwater, Gloria [Department of Biostatistics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Groth, Jeff [Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Palta, Manisha; Dewhirst, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Barry, William T. [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Duffy, Eileen A. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); and others

    2015-07-15

    Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should

  17. Imatinib

    Science.gov (United States)

    ... types of leukemia (cancer that begins in the white blood cells) and other cancers and disorders of ... In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has ...

  18. Compound list: imatinib, methanesulfonate salt [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available imatinib, methanesulfonate salt IMA 00186 ftp://ftp.biosciencedbc.jp/archive/open-t...ggates/LATEST/Rat/in_vivo/Liver/Single/imatinib%2C_methanesulfonate_salt.Rat.in_vivo.Liver.Single.zip ...

  19. Endocrine pancreatic function in combined treatment of gastric cancer patients with preoperative gamma therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bedzizheva, T B; Berdov, B A; Bassalyk, L S; Gromova, N V [Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii

    1982-06-01

    The results of a study are presented of the basal level of insulin and glucagon in gastric cancer patients, Stages 2-4, and in practically healthy subjects. The examination of the basal level of these hormones in the patients was repeated following preoperative irradiation and radical surgical treatment of the stomach. The function of the ..beta..-cells of the pancreatic insular apparatus was studied in gastric cancer patients using the glucose tolerance test. The basal level of insulin and glucagon before theatment in the entire group of patients did not significantly differ from that in the group of healthy persons. Preoperative irradiation of patients caused changes in the concentration of insulin and glucagon in the blood; 2 types of reactions were revealed: in patients with an initially low level of insulin and a high level of glucagon irradiation caused an increase in the content of blood insulin; in patients with the normal content of these hormones irradiation resulted in a considerable decrease of the insulin content.

  20. Does Pre-Operative Multiple Immunosuppressive Therapy Associate with Surgical Site Infection in Surgery for Ulcerative Colitis.

    Science.gov (United States)

    Uchino, Motoi; Ikeuchi, Hiroki; Bando, Toshihiro; Hirose, Kei; Hirata, Akihiro; Chohno, Teruhiro; Sasaki, Hirofumi; Takahashi, Yoshiko; Takesue, Yoshio; Hida, Nobuyuki; Hori, Kazutoshi; Nakamura, Shiro

    2015-01-01

    Almost all surgeries for ulcerative colitis (UC) are performed under immunosuppressive conditions. Immunomodulators or biologics, with the exception of corticosteroids, do not appear to be risk factors for post-operative infectious complications. However, many patients are on multiagent immunosuppressive therapy at the time of surgery. Therefore, we evaluated the influence of pre-operative multiple immunosuppressives on the occurrence of surgical site infection (SSI) in UC. We reviewed surveillance data from 181 patients who underwent restorative proctocolectomy between January 2012 and March 2014. The incidences of SSI and the possible risk factors among patients receiving different immunosuppressive therapies were compared and analyzed. The incidence of incisional (INC) SSI was 13.3% and that of organ/space (O/S) SSI was 7.2%. The number of immunosuppressives did not significantly correlate with each incidence. Total prednisolone administration ≥12,000 mg (OR 2.6) and an American Society of Anesthesiologists score ≥3 (OR 2.8) were shown to be independent risk factors for overall SSI, whereas corticosteroid use in INC SSI (OR 17.4) and severe disease (OR 5.2) and a large amount of blood loss (OR 3.9) in O/S SSI were identified as risk factors. Although a correlation between multiple immunosuppressive therapy and SSIs was not found, it is not recommended that all patients be treated with multiple immunosuppressive therapy. Treatment strategy should be applied based on the patient's condition. © 2015 S. Karger AG, Basel.

  1. Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Ye J. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Chan W. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Roh, Seon A. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Cho, Dong H. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do (Korea, Republic of); Park, Jong L.; Kim, Seon Y. [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Kim, Jong H. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun K. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Yong S., E-mail: yongsung@kribb.re.kr [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Jin C., E-mail: jckim@amc.seoul.kr [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of)

    2015-03-01

    Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types.

  2. Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Neil B.; Sidhu, Manpreet K.; Baby, Rekha [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Moss, Rebecca A.; Nissenblatt, Michael J. [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Lu, Shou-En [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

    2016-04-01

    Purpose/Objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results: During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

  3. Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.

    Science.gov (United States)

    Newman, Neil B; Sidhu, Manpreet K; Baby, Rekha; Moss, Rebecca A; Nissenblatt, Michael J; Chen, Ting; Lu, Shou-En; Jabbour, Salma K

    2016-04-01

    To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    International Nuclear Information System (INIS)

    Ha, Ye J.; Kim, Chan W.; Roh, Seon A.; Cho, Dong H.; Park, Jong L.; Kim, Seon Y.; Kim, Jong H.; Choi, Eun K.; Kim, Yong S.; Kim, Jin C.

    2015-01-01

    Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types

  5. Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Park, Hee Chul; Janjan, Nora A.; Mendoza, Tito R.; Lin, Edward H.; Vadhan-Raj, Saroj; Hundal, Mandeep; Zhang Yiqun; Delclos, Marc E.; Crane, Christopher H.; Das, Prajnan; Wang, Xin Shelley; Cleeland, Charles S.; Krishnan, Sunil

    2009-01-01

    Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

  6. The Effect of Preoperative Cognitive Behavior and Exercise Therapy for a Patient With an Implanted Left Ventricular Assist Device in Korea.

    Science.gov (United States)

    Seo, Yong Gon; Park, Won Hah; Jeon, Eun Seok; Sung, Ji Dong; Jang, Mi Ja

    2017-10-01

    Left ventricular assist devices (LVADs) are used in patients with progressive heart failure symptoms to provide circulatory support. Patients with LVADs are referred to inpatient cardiac rehabilitation to prevent postoperative complications and improve aerobic capacity and quality of life. Preoperative exercise therapy for cardiac patients is an emerging treatment modality, and several studies have reported that it improves postoperative outcomes, such as length of hospital stay and postoperative complications. This case report describes the benefits of preoperative cognitive behavioral and exercise therapy in a Korean patient undergoing LVAD implantation. V. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  7. Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity.

    Science.gov (United States)

    Basciani, Sabrina; Brama, Marina; Mariani, Stefania; De Luca, Gabriele; Arizzi, Mario; Vesci, Loredana; Pisano, Claudio; Dolci, Susanna; Spera, Giovanni; Gnessi, Lucio

    2005-03-01

    Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.

  8. Aneurysmal bone cyst of the mandible managed by conservative surgical therapy with preoperative embolization

    Energy Technology Data Exchange (ETDEWEB)

    An, Seo Young [School of Dentistry, Kyungpook National University, Daegu (Korea, Republic of)

    2012-03-15

    A 9-year-old girl visited our hospital, complaining of a rapid-growing and rigid swelling on the left posterior mandibular area. Panoramic radiograph showed a moderately defined multilocular honeycomb appearance involving the left mandibular body. CT scan revealed an expansile, multilocular osteolytic lesion and multiple fluid levels within cystic spaces. Bone scan demonstrated increased radiotracer uptake and angiography showed a highly vascularized lesion. The lesion was suspected as aneurysmal bone cyst (ABC) and preoperative embolization was performed, which minimize the extent of operation and the surgical complication. The lesion was treated by surgical curettage and lateral decortication with repositioning. No additional treatment such as a surgical reconstruction or bone graft was needed. Early diagnosis of ABC is very important and appropriate treatment should be performed considering several factors such as age, surgical complication, and possibility of recurrence.

  9. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Kristiansen, C.; Loft, A.; Berthelsen, Anne Kiil

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography Udgivelsesdato: 2008/1...... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared to histopathologic...

  10. PET/CT and Histopathologic Response to Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer

    DEFF Research Database (Denmark)

    Kristiansen, Charlotte; Loft, Annika; Berthelsen, Anne K

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography....... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral(R) (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared...

  11. Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Ho; Hong, Yong Sang [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Yangsoon; Kim, Jihun [Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jeong Eun; Kim, Kyu-pyo; Kim, Sun Young [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Jin-hong; Kim, Jong Hoon [Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, In Ja; Lim, Seok-Byung; Yu, Chang Sik; Kim, Jin Cheon [Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Tae Won, E-mail: twkimmd@amc.seoul.kr [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2016-10-01

    Purpose: Preoperative chemoradiation therapy (CRT) with capecitabine is a standard treatment strategy in patients with locally advanced rectal cancer (LARC). Temozolomide improves the survival of patients with glioblastoma with hypermethylated O{sup 6}-methylguanine DNA methyltransferase (MGMT); MGMT hypermethylation is one of the colorectal carcinogenesis pathways. We aimed to determine the dose-limiting toxicity (DLT) and recommended dose (RD) of temolozomide in combination with capecitabine-based preoperative CRT for LARC. Methods and Materials: Radiation therapy was delivered with 45 Gy/25 daily fractions with coned-down boost of 5.4 Gy/3 fractions. Concurrent chemotherapy comprised fixed and escalated doses of capecitabine and temozolomide, respectively. The MGMT hypermethylation was evaluated in pretreatment tumor samples. This trial is registered with (ClinicalTrials.gov) with the number (NCT01781403). Results: Twenty-two patients with LARC of cT3-4N0 or cT{sub any}N1-2 were accrued. Dose level 3 was chosen as the RD because DLT was noticeably absent in 10 patients treated up to dose level 3. An additional 12 patients were recruited in this group. Grade III adverse events were noted, and pathologic complete response (pCR) was observed in 7 patients (31.8%); MGMT hypermethylation was detected in 16. The pCR rate was 37.5% and 16.7% in the hypermethylated and unmethylated MGMT groups, respectively (P=.616). Conclusions: There was a tendency toward higher pCR rates in patients with hypermethylated MGMT. Future randomized studies are therefore warranted.

  12. Surgical Outcome of Intermittent Exotropia With Improvement in Control Grade Subsequent to Part-time Preoperative Occlusion Therapy.

    Science.gov (United States)

    Bang, Seung Pil; Lee, Dong Cheol; Lee, Se Youp

    2018-01-01

    To evaluate the effect of improvement in the control grade of intermittent exotropia using part-time occlusion therapy on the final postoperative outcome. Control of intermittent exotropia was graded as good, fair, or poor in 89 consecutive patients with intermittent exotropia during their first visit. The patients were reevaluated after part-time preoperative occlusion therapy and divided into two groups (improvement and no improvement) according to whether they showed improvement in control grade. The surgical success rate was compared retrospectively between the two groups. The mean angle of deviation on the first visit was 27.61 ± 5.40 prism diopters (PD) at distance and 29.82 ± 5.28 PD at near. There were significant improvements in the angles of deviation for distance (26.17 ± 5.09 PD) and near (27.26 ± 5.56 PD) after part-time occlusion (both P Part-time occlusion therapy improves the control grade of intermittent exotropia, leading to a better likelihood of successful surgery and a reduction of the angles of deviation for distance and near. [J Pediatr Ophthalmol Strabismus. 2018;55(1):59-64.]. Copyright 2017, SLACK Incorporated.

  13. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, Gleevec™

    Directory of Open Access Journals (Sweden)

    Martin Henkes

    2008-03-01

    Full Text Available 1Martin Henkes, 2Heiko van der Kuip, 1Walter E Aulitzky12nd Department of Internal Medicine, Oncology and Hematology, Robert Bosch Hospital, Auerbachstr. 110, Stuttgart, Germany; 2Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, Stuttgart, and University of Tuebingen, GermanyAbstract: Treatment options for chronic myeloid leukemia (CML have changed dramatically during the last decades. Interferon-α treatment and stem cell transplantation (SCT clearly improved survival over conventional chemotherapy and offered the possibility of complete and durable responses. With the advent of the small molecule inhibitor imatinib mesylate (Glivec®, GleevecTM targeting the causative Bcr-Abl oncoprotein, the era of molecular cancer therapy began with remarkable success especially in chronic phase patients. Today, imatinib is the first-line treatment for CML. However, imatinib does not appear to be capable to eliminate all leukemia cells in the patients and pre-existing as well as acquired resistance to the drug has been increasingly recognized. To overcome these problems, several strategies involving dose escalation, combinations with other agents, and novel Bcr-Abl inhibitors have been developed.Keywords: CML therapy, imatinib, SCT, novel kinase inhibitors

  14. Adoption of Preoperative Radiation Therapy for Rectal Cancer From 2000 to 2006: A Surveillance, Epidemiology, and End Results Patterns-of-Care Study

    International Nuclear Information System (INIS)

    Mak, Raymond H.; McCarthy, Ellen P.; Das, Prajnan; Hong, Theodore S.; Mamon, Harvey J.; Hoffman, Karen E.

    2011-01-01

    Purpose: The German rectal study determined that preoperative radiation therapy (RT) as a component of combined-modality therapy decreased local tumor recurrence, increased sphincter preservation, and decreased treatment toxicity compared with postoperative RT for rectal cancer. We evaluated the use of preoperative RT after the presentation of the landmark German rectal study results and examined the impact of tumor and sociodemographic factors on receiving preoperative RT. Methods and Materials: In total, 20,982 patients who underwent surgical resection for T3-T4 and/or node-positive rectal adenocarcinoma diagnosed from 2000 through 2006 were identified from the Surveillance, Epidemiology, and End Results tumor registries. We analyzed trends in preoperative RT use before and after publication of the findings from the German rectal study. We also performed multivariate logistic regression to identify factors associated with receiving preoperative RT. Results: Among those treated with RT, the proportion of patients treated with preoperative RT increased from 33.3% in 2000 to 63.8% in 2006. After adjustment for age; gender; race/ethnicity; marital status; Surveillance, Epidemiology, and End Results registry; county-level education; T stage; N stage; tumor size; and tumor grade, there was a significant association between later year of diagnosis and an increase in preoperative RT use (adjusted odds ratio, 1.26/y increase; 95% confidence interval, 1.23-1.29). When we compared the years before and after publication of the German rectal study (2000-2003 vs. 2004-2006), patients were more likely to receive preoperative RT than postoperative RT in 2004-2006 (adjusted odds ratio, 2.35; 95% confidence interval, 2.13-2.59). On multivariate analysis, patients who were older, who were female, and who resided in counties with lower educational levels had significantly decreased odds of receiving preoperative RT. Conclusions: After the publication of the landmark German rectal

  15. Phase I study of imatinib, cisplatin and 5-fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Mayr Martina

    2012-12-01

    Full Text Available Abstract Background Despite all benefit provided by established therapies prognosis of gastric cancer remains poor. Targeted inhibition of platelet derived growth factor receptor (PDGFR by imatinib may influence tumor growth and amplify chemotherapeutic effects. Methods This phase I study evaluated dose limiting toxicity (DLT of imatinib combinated with chemotherapy according to a 3-patient cohort dose-escalating design. Thirty-five patients received cisplatin (60 mg/m2 d1 q 3w/ capecitabine (1250 mg/m2 bid d1-14 q 21 or cisplatin (50 mg/m2 d1 q 2w/ 5-fluoruracil (2 g/m2 d1, q 1w. Imatinib was started d - 4 with dose escalation from 300 to 700 mg QD in 100 mg steps. Results At imatinib dose level 1 (300mg one DLT was observed, three more patients were enrolled without further DLT. At dose level 5 (700 mg two gastric perforations occurred, so 600 mg imatinib emerged as the maximum tolerated dose. Major grade 3/4 toxicities were nausea (6%, anemia (6% and fatigue (3%. Response evaluation revealed partial response in 27% and stable disease in 43% of the assessable patients. Conclusions Combination of imatinib and chemotherapy is well tolerated. Response rates were not superior to those of standard therapy. Further investigations of a larger group of patients are required to confirm the amplification of chemotherapy effects by imatinib. Trial registration European Clinical Trials Database: Eudra-CT2006-005792-17 and Clinical Trials Database: NCT00601510

  16. E-cadherin and Vimentin as Predictors of Resistance to Preoperative Systemic Therapy in Patients with Advanced Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sonar. S. Panigoro

    2017-01-01

    Full Text Available Loss of E-cadherin and increased vimentin expression are associated with epithelial-mesenchymal transition andcancer stemness which are responsible for treatment resistance. The study aims to evaluate the role of E-cadherin andvimentin as predictors of resistance to preoperative systemic therapy in patients with advanced breast cancer. This wasa cross-sectional analytical study in patients with stage III-IV breast cancer in Dharmais Cancer Hospital and dr. CiptoMangunkusumo National Hospital from July 2015 to April 2016. Patients had biopsy specimens embedded in paraffinblocks. Expressions of E-cadherin and vimentin proteins were done immunohistochemically. Treatment response wasevaluated histopathologically using Miller-Payne criteria on mastectomy specimens. A total of 65 patients were enrolled.Five patients with invasive lobular carcinoma were excluded. Thirty one had chemotherapy and 29 had hormonaltherapy. After treatment, 46 patients were eligible for mastectomy. E-cadherin and vimentin were positive in 28 (60.9%and 11 (20.3% of specimens. Twenty-three (50% patients showed no response. Treatment resistance were associatedwith type of therapy (OR=4.4; 95% CI=1.27-15.41; p=0.017 and vimentin expression (OR=6.75; 95% CI=1.27-30.02;p=0.016. Hormonal therapy (ORadj=6.26; 95%CI=1.59-24.6; p=0.009 and positive vimentin (ORadj=8.75; 95%CI=1.43-57.4; p=0.019 were independent predictors of treatment resistance. In conclusion, E-cadherin and vimentin can beused as predictors of resistance to preoperative systemic therapy in patients with advanced breast cancer. Keywords: breast cancer, cancer stemness, E-cadherin, preoperative therapy, vimentin.   Peran E-cadherin dan Vimentin sebagai Prediktor Resistensi Terapi Sistemik Preoperatif pada Pasien Kanker Payudara Stadium Lanjut Abstrak Hilangnya ekspresi E-cadherin dan meningkatnya ekspresi vimentin dihubungkan dengan epithelial-mesenchymaltransition dan cancer stemness yang bertanggungjawab terhadap

  17. Preoperative home-based physical therapy versus usual care to improve functional health of frail older adults scheduled for elective total hip arthroplasty: A pilot randomized controlled trial

    NARCIS (Netherlands)

    Oosting, E.; Jans, M.P.; Dronkers, J.J.; Naber, R.H.; Dronkers-Landman, C.M.; Appelman-De Vries, S.M.; Meeteren, N.L. van

    2012-01-01

    Preoperative home-based physical therapy versus usual care to improve functional health of frail older adults scheduled for elective total hip arthroplasty: a pilot randomized controlled trial. Objective: To investigate the feasibility and preliminary effectiveness of a home-based intensive exercise

  18. Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal

    leukemia along with imatinib, all of which vary in their effectiveness against mutated BCR-ABL forms, detection of pre-existing BCR-ABL mutations can help in selection of appropriate first-line drug therapy. Thus, mutation testing using CD34+ cells may facilitate improved, patient-tailored treatment.

  19. Preoperative physical therapy treatment did not influence postoperative pain and disability outcomes in patients undergoing shoulder arthroscopy: a prospective study

    Directory of Open Access Journals (Sweden)

    Valencia C

    2016-07-01

    Full Text Available Carolina Valencia,1 Rogelio A Coronado,2 Corey B Simon,3,4 Thomas W Wright,5 Michael W Moser,5 Kevin W Farmer,5 Steven Z George3,6,7 1Department of Applied Medicine and Rehabilitation, Indiana State University, Terre Haute, IN, 2Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN, 3Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, FL, 4Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville,FL, 5Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville, FL, 6Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL, 7Brooks–PHHP Research Collaboration, Jacksonville, FL, USA Background: There is limited literature investigating preoperative physical therapy (pre-op PT treatment on pain intensity and disability after musculoskeletal surgery. The purposes of the present cohort study were to describe patient characteristics for those who had and did not have pre-op PT treatment and determine whether pre-op PT influenced the length of postoperative physical therapy (post-op PT treatment (number of sessions and 3-month and 6-month postsurgical outcomes, such as pain intensity and disability. Patients and methods: A total of 124 patients (mean age =43 years, 81 males with shoulder pain were observed before and after shoulder arthroscopic surgery. Demographic data, medical history, and validated self-report questionnaires were collected preoperatively and at 3 months and 6 months after surgery. Analysis of variance models were performed to identify differences across measures for patients who had pre-op PT treatment and those who did not and to examine outcome differences at 3 months and 6 months. Alpha was set at the 0.05 level for statistical significance. Results: Males had less participation in pre-op PT than females (P=0.01. In

  20. The use of imatinib in the treatment of inoperable dermatofibrosarcoma protuberans in the area of the shoulder joint

    Directory of Open Access Journals (Sweden)

    Joanna Huszno

    2014-06-01

    Full Text Available Introduction. Dermatofibrosarcoma protuberans (DFSP is a rare sarcoma of the skin and subcutaneous tissue. The most common clinical problem is its local recurrence. The therapeutic procedure of choice is radical surgery. In the case of inoperable disease, targeted therapy with imatinib, a tyrosine kinase inhibitor, may cause significant reduction of tumor volume and even enable radical surgery. Objective. We present the effectiveness of imatinib for the treatment of unresectable DFSP localized in the area of the shoulder joint of a 62-year-old woman. Case report. The patient met the criteria for inclusion in treatment with imatinib. After 3 cycles of treatment, partial regression of the lesions (above 50% was observed. Therapy was complicated by hepatological side effects during the sixth cycle. Treatment was continued with a reduced dose when transaminase levels normalized. In a physical examination and imaging studies, further regression was observed. The patient has regained considerable mobility of the shoulder joint. A decision to continue the treatment has been made. Conclusions. The use of imatinib allowed a clinical benefit to be gained in the form of significant regression of lesions. A very good treatment response and significant improvement in quality of life of the patient were achieved. The patient has been treated with imatinib for 30 months.

  1. Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Nomura, Tomoko; Murakami, Ryuji; Toya, Ryo; Teshima, Keiko; Nakahara, Aya; Hirai, Toshinori; Hiraki, Akimitsu; Nakayama, Hideki; Yoshitake, Yoshihiro; Ota, Kazutoshi; Obayashi, Takehisa; Yamashita, Yasuyuki; Oya, Natsuo; Shinohara, Masanori

    2010-01-01

    Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m 2 /day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

  2. Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

    International Nuclear Information System (INIS)

    Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Rhodes, C. Harker; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

    2013-01-01

    Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to

  3. [Watermelon stomach: Chronic renal failure and/or imatinib?].

    Science.gov (United States)

    Montagnac, Richard; Blaison, Dominique; Brahimi, Saïd; Schendel, Adeline; Levasseur, Thomas; Takin, Romulus

    2015-11-01

    Watermelon stomach or gastric antral vascular ectasia (GAVE) syndrome is an uncommon cause of sometimes severe upper gastro-intestinal bleeding. Essentially based on a pathognomonic endoscopic appearance, its diagnosis may be unrecognised because mistaken with portal hypertensive gastropathy, while treatment of these two entities is different. Its etiopathogeny remains still unclear, even if it is frequently associated with different systemic illnesses as hepatic cirrhosis, autoimmune disorders and chronic renal failure. The mechanism inducing these vascular ectasia may be linked with mechanical stress on submucosal vessels due to antropyloric peristaltic motility dysfunction modulated by neurohormonal vasoactive alterations. Because medical therapies are not very satisfactory, among the endoscopic modalities, argon plasma coagulation seems to be actually the first-line treatment because the most effective and safe. However, surgical antrectomy may be sometimes necessary. Recently GAVE syndrome appeared as a new adverse reaction of imatinib mesylate, one of the tyrosine kinase inhibitors used in chronic myeloid leukemia, and we report here the observation of such a pathology in one patient treated at the same time by haemodialysis and by imatinib mesylate for chronic myeloid leukemia. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  4. Effect of Imatinib on the Oogenesis and Pituitary -Ovary Hormonal Axis in Female Wistar Rat

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    Parichehreh Yaghmaei

    2009-01-01

    Full Text Available Background: Imatinib mesylate, a small-molecular analog of adenosine triphosphate (ATPthat potently inhibits tyrosine kinase activities of Bcr–Abl, PDGFR-β, PDGFR-α, c-Fms, Argand c-kit, is one of the novel molecularly targeted drugs being introduced into cancer therapy.We tested the effect of imatinib on the ovarian histological structure and the concentration ofestrogen and progesterone, luteinizing hormone (LH and follicle stimulating hormone (FSHin the serum of female Wistar rats.Materials and Methods: Two groups of rats (180 ± 15 grams were gavaged with doses of 50and 100 mg/kg body weight imatinib dissolved in distilled water for 14 days. The control groupreceived sterile water. On day 7, after termination of the treatment, blood serum concentrationwas measured with the radioimmunoassay (RIA method. Also, sections (5 μm thick of ovariesstained with hematoxylin and eosin (H&E were investigated histologically.Results: Progesterone concentration in the experimental groups was increased (p<0.001,estrogen and FSH concentrations were decreased (p<0.01, and the LH concentration decreasedbut was not statistically different in comparison with the control group. The weight of ovaries andnumber of atretic follicles in the experimental groups was increased compared with the controlgroup (p<0.05. The diameter of corpus lutea were increased but the number of corpus luteadecreased in both experimental groups (p<0.01.Conclusion: These findings suggest that administration of imatinib may have profound effects onfemale fertility.

  5. Behandling af ideopatisk hypereosinofilt syndrom med imatinib

    DEFF Research Database (Denmark)

    Sørensen, Anne Louise; Larsen, Herdis

    2008-01-01

    We here report a case of idiopathic hypereosinophilic syndrome with prompt response to treatment with imatinib. The patient presented with chest pain, myalgias, fatigue and weakness. Blood tests and bone marrow examination revealed striking eosinophilia. Clonal or reactive disorders were excluded...

  6. Clinical outcome during the peri-operative (thyroidectomy) period of severely hyperthyroid patients with normalized pre-operative free-T4 levels: Importance of I-131 therapy as a part of pre-operative preparation

    International Nuclear Information System (INIS)

    Siguan-Crisaldo, M.A.L.; Mercado-Asis, L.B.

    2005-01-01

    Thyroidectomy is performed for hyperthyroidism on patients who do not respond to or are not compliant with medical therapy and in patients with very large goiters causing compressive symptoms. All thyrotoxic patients undergoing thyroidectomy usually are first treated with anti-thyroid drugs to normalize free thyroid hormone levels and render them euthyroid before surgery in order to prevent complications particularly thyroid storm and circulatory collapse. In this case series, we describe the clinical outcome during the perioperative (thyroidectomy) period of three severely hyperthyroid patients, two females and one male, with ages ranging from 13 to 38 years. All patients had grade III goiter, and only one had exophthalmos. The mean duration of goiter was 3.6 years. All of them were given preoperative treatment consisting of propylthiouracil (PTU) at 450-600 mg/day; iodone, 3 tablets daily and propranolol at 30-120 mg/day for one month. All of them had normalized preoperative thyroid function tests. In addition to the preoperative medications mentioned above, all three patients received radioactive iodine therapy before surgery. The first two patients received relatively low doses of 8.0 and 7.5 mCi of I-131 respectively. Unfortunately the first patient had supraventricular tachycardia (SVT), post skin cutting and the other one went into thyroid storm. The third patient who received a cumulative dose of 23.5 mCi of I-131 before surgery had an uneventful postoperative course. It is concluded that normalization of thyroid hormone parameters, especially free T4 is not sufficient for an uneventful and uncomplicated peri-thyroidectomy period in severely hyperthyroid patients with large goiters. Effective radioactive iodine therapy might prove to be helpful in inducing thyroid tissue fibrosis, thus leading to true clinical euthyroidism and excellent clinical course postoperatively. (author)

  7. Imatinib as the first and only treatment in Europe for adult patients at significant risk of relapse following gastrointestinal stromal tumor removal

    Science.gov (United States)

    Duffaud, F; Salas, S; Huyn, T; Deville, JL

    2010-01-01

    Mutations of the KIT gene are the molecular hallmark of most gastrointestinal stromal tumors (GISTs). GIST has become a model for targeted treatment of solid tumors, imatinib becoming the standard first-line treatment of these tumors in the advanced/metastatic phase. Because of the efficacy of imatinib treatment in the advanced setting, its role following resection of a primary non-metastatic GIST was investigated. The recently published phase III, double-blind, placebo-controlled, multicenter ACOSOG Z9001 study showed that adjuvant therapy is safe, and significantly improves recurrence-free survival compared to placebo when given after resection. To what extent imatinib will improve overall survival has yet to be answered. What is clear is that high-risk GIST patients definitely need adjuvant therapy, and that 1 year of imatinib is not enough for the patients who do need it. The questions of optimal duration of imatinib treatment in the adjuvant setting, adequate selection of risk patients and effect of imatinib on overall survival are currently being studied. PMID:21694845

  8. Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer

    International Nuclear Information System (INIS)

    Minsky, Bruce D.; Cohen, Alfred M.; Enker, Warren E.; Saltz, Leonard; Guillem, Jose G.; Paty, Philip B.; Kelsen, David P.; Kemeny, Nancy; Ilson, David; Bass, Joanne; Conti, John

    1997-01-01

    Purpose: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. Methods and Materials: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. Results: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). Conclusion: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response

  9. Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate.

    Science.gov (United States)

    Pompetti, Franca; Spadano, Antonio; Sau, Antonella; Mennucci, Antonio; Russo, Rosa; Catinella, Virginia; Franchi, Paolo Guanciali; Calabrese, Giuseppe; Palka, Giandomenico; Fioritoni, Giuseppe; Iacone, Antonio

    2007-04-01

    BCR/ABL-positive acute myeloid leukemia (AML) is a rare disease, characterized by a poor prognosis, with resistance to induction chemotherapy and frequent relapses in responsive patients. Here we report a case of BCR/ABL-positive AML-M6 who, after relapse, was treated with Imatinib Mesylate (600 mg/die) and within 4 months achieved a cytogenetic and molecular complete response. After more than 4 years of continuous Imatinib therapy, nested RT-PCR for BCR/ABL is persistently negative. The case reported shows that the response obtained with Imatinib Mesylate in BCR/ABL-positive AML may be long lasting, offering a chance of successful treatment for this poor prognosis group of patients.

  10. Sphincter preservation with pre-operative radiation therapy (RT) and coloanal anastomosis: long term follow-up

    International Nuclear Information System (INIS)

    Wagman, Raquel; Minsky, Bruce D.; Cohen, Alfred M.; Guillem, Jose G.; Paty, Philip B.

    1997-01-01

    36 patients, cumulative local failure as a component of failure was crude: 17%, and 5-Yr actuarial: 21%. The 5-yr actuarial disease free survival was 60% and overall survival was 64%. A total of 9 Pts. were excluded from the analysis of sphincter function (8 underwent an APR, and 1: unresectable liver mets). In the remaining 27 eligible pts. sphincter function was: excellent: 59%, good: 26%, fair: 15%, and poor: 0%. The median number of bowel movements was 2 (range: 0-8). CONCLUSION: Our data suggest that pre-operative RT allows sphincter preservation in 77% of pts. who would otherwise require an APR and 85% have good to excellent sphincter function. Given the moderate local failure rate we now routinely use pre-operative combined modality therapy plus post-op chemotherapy for pts. with clinical T3 disease

  11. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: MANAGEMENT OF ACROMEGALY PATIENTS: WHAT IS THE ROLE OF PRE-OPERATIVE MEDICAL THERAPY?

    Science.gov (United States)

    Fleseriu, Maria; Hoffman, Andrew R; Katznelson, Laurence

    2015-06-01

    Acromegaly is a complex disease characterized by growth hormone (GH) excess originating in most cases from a pituitary tumor. The goals of treatment include removing the tumor or reducing tumor burden, normalizing GH secretion and insulin-like growth factor 1 levels, and preserving normal pituitary function if possible. Surgery by an experienced neurosurgeon is still considered first-line therapy, especially in cases with small tumors. In the last few decades, significant progress in the development of selective pharmacologic agents has greatly facilitated the management of active acromegaly, with agents such as somatostatin-receptor ligands (SRLs), GH-receptor antagonists, and dopamine agonists. In addition to adjuvant treatment, pre-operative medical therapy and primary therapy in de novo patients are increasingly employed. A United States National Library of Medicine PubMed search (through July 2014) was conducted for the following terms: acromegaly, pre-operative medical therapy, somatostatin-receptor ligands, and somatostatin analogs. Articles not in English and those not in peer-reviewed journals were excluded. In reviewing pertinent articles, focus was placed on biochemical and other postoperative outcomes of medical therapy. An analysis of the full effect of pre-operative use of SRLs on surgical outcomes (remission rates and peri-operative complications) is limited by heterogeneity of methodology, low overall surgical cure rates, and different study designs. The assumption that SRL use prior to surgery reduces peri-operative surgical risk has yet to be proven. A variable degree of tumor shrinkage with preoperative SRLs is observed. Likewise, SRL treatment 3 months before surgery may improve surgical remission rates in the short term; however, positive results do not persist in the long term. We consider that medical therapy before surgery could play a role in carefully selected patients, but treatment should be individualized. Primary medical therapy with a

  12. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol

    2010-01-01

    Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.......Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

  13. Hematologic Relapse after 2 Years on a Non-Authorized Copy Version of Imatinib in a Patient with Chronic Myeloid Leukemia in Chronic Phase: A Case Report

    Directory of Open Access Journals (Sweden)

    Zoubir Chouffai

    2010-07-01

    Full Text Available Imatinib (Gleevec®/Glivec® has demonstrated high and durable hematologic and cytogenetic response rates, favorable safety and toxicity profiles, and prolonged survival when used for the treatment of chronic myeloid leukemia (CML. Imatinib copy drugs are currently available in some countries; however, the safety and efficacy of these compounds have not been widely assessed. We present a patient who received the copy drug imatinib-COPER, lost hematologic response while on therapy, and was subsequently treated with branded Glivec. This report, and other published cases, suggests that imatinib copy drugs may not be equivalent to branded Glivec in pharmacology, safety, and efficacy. The case was a 42-year-old Moroccan male with CML. Initial therapy with hydroxyurea alone followed by hydroxyurea in combination with interferon-α resulted in durable complete hematologic remission (CHR. Due to adverse effects, the patient was switched to imatinib-COPER at 400 mg/day. Despite compliance with therapy, he lost his CHR after 2 years and presented with aplasia requiring a blood transfusion. Administration of Glivec in combination with hydroxyurea resulted in re-achievement of complete hematologic remission that was stable at last follow-up. Data from large-scale trials demonstrating high and durable responses and favorable safety have resulted in Glivec being considered as standard frontline therapy for patients with CML. Such trials have not been conducted for imatinib copy drugs. In the absence of clinical trial data, information from individual cases is critical to assessing the utility of copy drugs. This report suggests that initial treatment with an imatinib copy drug may compromise efficacy.

  14. Impact of imatinib interruption and duration of prior hydroxyurea on the treatment outcome in patients with chronic myeloid leukemia: Single institution experience

    International Nuclear Information System (INIS)

    Edesa, W.A.; Abdel-malek, R.R.

    2015-01-01

    Background: Optimal response requires that patients should be maintained on the drug continuously. Objectives: To evaluate the influence of imatinib interruption and prior hydroxyurea use on the outcome of patients with chronic myeloid leukemia. Materials and methods: Between January 2010 and November 2013, patients with chronic phase who received imatinib at the Kasr Al-ainy Center of Clinical Oncology were included. Results: Sixty patients were included in this study, thirty three patients (55%) received imatinib upfront, while 27 (45%) received imatinib post hydroxyurea. Imatinib was not given regularly in 50% of patients. In terms of response, only major molecular response and complete molecular response were statistically significant in favor of patients who were receiving imatinib regularly compared to those who had interruption (ρ < 0.001, ρ < 0.001, respectively) , while there was no difference in patients stratified according to prior hydroxyurea. The median progression free survival was 30.3 months (95% CI 24.3–36.3). Among the group of patients who received imatinib regularly, progression free survival was longer (ρ = 0.049), there was no difference between those who received prior hydroxyurea versus those who did not (ρ = 0.67). Conclusion: Duration of prior hydroxyurea had no impact on response or progression free survival, while patients regular on imatinib had statistically significant difference with respect to major molecular response, complete molecular response and progression free survival compared to those who had periods of drug interruption, thus we need more governmental support to supply the drug without interruption to improve the outcome of therapy

  15. Successful Treatment For Chronic Eosinophilic Leukemia (CEL With Imatinib Mesylate

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    Rayane da Silva Souza

    2017-12-01

    Full Text Available We report a case of a patient with Chronic Eosinophilic Leukemia (CEL with mutation in alfa PDGFR gene exhibiting a satisfactory response to treatment with imatinib mesylate. A 25-year-old man presented in a hematology service with a persistent cough and hemogram alterations. His blood count showed a hemoglobin level of 12.5 g/dL and a white blood cell count of 94,030/mm3, eosinophils were 68% of all cells. Bone marrow aspiration and biopsy showed hypercellularity with marked eosinophilia (77% and erythroid differentiation series was hypocellular with normoblast maturation. The immunohistochemically of the bone biopsy was positive for myeloperoxidase and negative for CD34/CD99, consistent with CEL. Fluorescence in situ hybridization (FISH for the beta-fraction of platelet-derived growth factor (PDGFRβ and Philadelphia chromosome (Ph 1 were negative and the alfa PDGFR (Platelet-Derived Growth Factor was positive and showed heterozygosis in c.2531T>C on 18 Exon and homozygous in C.2562+1G>A at the region of the splicing site at the 18 intron. Treatment was initiated and maintained by administering 400mg/day imatinib mesylate. Laboratory findings returned to normal ranges, with clinical improvement and a hematological response observed after the second month of therapy. Currently, the patient’s blood count shows the white blood cell count (5,400 total leukocytes, eosinophils (8.6/mm3, hemoglobin (15.5 g/dl, hematocrit (45.4% and platelets (298,000/mm3 within normal ranges. The mutation search was negative in in peripheral blood one year after the initial treatment. Our work corroborates other studies on the efficacy of imatinib mesylate in the treatment of patients with CSF PDGFR alpha positive. We emphasize the importance of molecular studies, considering its relevance for the correct staging of the disease. Since CEL is a rare disease, it is important to define its etiology and anticipate its treatment, thus minimizing the damage induced by

  16. GSTT1 copy number gain and ZNF overexpression are predictors of poor response to imatinib in gastrointestinal stromal tumors.

    Directory of Open Access Journals (Sweden)

    Eui Jin Lee

    Full Text Available Oncogenic mutations in gastrointestinal stromal tumors (GISTs predict prognosis and therapeutic responses to imatinib. In wild-type GISTs, the tumor-initiating events are still unknown, and wild-type GISTs are resistant to imatinib therapy. We performed an association study between copy number alterations (CNAs identified from array CGH and gene expression analyses results for four wild-type GISTs and an imatinib-resistant PDGFRA D842V mutant GIST, and compared the results to those obtained from 27 GISTs with KIT mutations. All wild-type GISTs had multiple CNAs, and CNAs in 1p and 22q that harbor the SDHB and GSTT1 genes, respectively, correlated well with expression levels of these genes. mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.041, whereas mRNA expression levels of VEGF (P=0.025, IGF1R (P=0.026, and ZNFs (P<0.05 were significantly higher in GISTs with wild-type/PDGFRA D842V mutations than GISTs with KIT mutations. qRT-PCR validation of the GSTT1 results in this cohort and 11 additional malignant GISTs showed a significant increase in the frequency of GSTT1 CN gain and increased mRNA expression of GSTT1 in wild-type/PDGFRA D842V GISTs than KIT-mutant GISTs (P=0.033. Surprisingly, all four malignant GISTs with KIT exon 11 deletion mutations with primary resistance to imatinib had an increased GSTT1 CN and mRNA expression level of GSTT1. Increased mRNA expression of GSTT1 and ZNF could be predictors of a poor response to imatinib. Our integrative approach reveals that for patients with wild-type (or imatinib-resistant GISTs, attempts to target VEGFRs and IGF1R may be reasonable options.

  17. The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice.

    Directory of Open Access Journals (Sweden)

    Laurent L Reber

    Full Text Available Gouty arthritis is caused by the deposition of monosodium urate (MSU crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Here we demonstrate that treatment with the tyrosine kinase inhibitor imatinib mesylate (imatinib can suppress inflammation induced by injection of MSU crystals into subcutaneous air pouches or into the ankle joint of wild type mice. Moreover, imatinib treatment also largely abolished the lower levels of inflammation which developed in IL-1R1-/- or KitW-sh/W-sh mice, indicating that this drug can inhibit IL-1-independent pathways, as well as mast cell-independent pathways, contributing to pathology in this model. Imatinib treatment not only prevented ankle swelling and synovial inflammation when administered before MSU crystals but also diminished these features when administrated after the injection of MSU crystals, a therapeutic protocol more closely mimicking the clinical situation in which treatment occurs after the development of an acute gout flare. Finally, we also assessed the efficiency of local intra-articular injections of imatinib-loaded poly(lactic-co-glycolic acid (PLGA nanoparticles in this model of acute gout. Treatment with low doses of this long-acting imatinib:PLGA formulation was able to reduce ankle swelling in a therapeutic protocol. Altogether, these results raise the possibility that tyrosine kinase inhibitors might have utility in the treatment of acute gout in humans.

  18. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Richard, Patrick, E-mail: patrjr@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Phillips, Mark; Smith, Wade [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Davidson, Darin [Department of Orthopedic Surgery, University of Washington, Seattle, Washington (United States); Kim, Edward; Kane, Gabrielle [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States)

    2016-07-01

    Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with the largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.

  19. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

    International Nuclear Information System (INIS)

    Richard, Patrick; Phillips, Mark; Smith, Wade; Davidson, Darin; Kim, Edward; Kane, Gabrielle

    2016-01-01

    Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with the largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.

  20. [Disappearance of a Philadelphia chromosome-positive clone and appearance of a -negative clone following treatment with imatinib mesylate in acute myelomonocytic leukemia].

    Science.gov (United States)

    Takahashi, Wataru; Arai, Yukihiro; Tadokoro, Jiro; Takeuchi, Kengo; Yamagata, Tetsuya; Mitani, Kinuko

    2006-02-01

    A 63-year-old female was diagnosed as having Philadelphia chromosome-positive acute myelomonocytic leukemia in June 2002. The patient received monotherapy with imatinib mesylate or combination therapy with DCM and idarubicin/cytarabine, both of which failed in attaining disease remission. However, the second imatinib administration plus CAG therapy resulted in disappearance of the Philadelphia chromosome-positive clone and increase of Philadelphia chromosome-negative cells. During a therapy-withholding period due to fungal infection, the Philadelphia chromosome-positive clone expanded and the patient died of cerebral hemorrhage in February 2003. The transient suppression of the Philadelphia chromosome-positive clone may have brought about amplification of the Philadelphia chromosome-negative cells after the secondary imatinib treatment.

  1. Platelet Dysfunction in Patients with Chronic Myeloid Leukemia: Does Imatinib Mesylate Improve It?

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    Olga Meltem Akay

    2016-05-01

    Full Text Available Objective: The aim of this study was to investigate the effects of imatinib mesylate on platelet aggregation and adenosine triphosphate (ATP release in chronic myeloid leukemia patients. Materials and Methods: Platelet aggregation and ATP release induced by 5.0 mM adenosine diphosphate, 0.5 mM arachidonic acid, 1.0 mg/ mL ristocetin, and 2 µg/mL collagen were studied by whole blood platelet lumi-aggregometer in 20 newly diagnosed chronic myeloid leukemia patients before and after imatinib mesylate treatment. Results: At the time of diagnosis, 17/20 patients had abnormal platelet aggregation results; 8 (40% had hypoactivity, 6 (30% had hyperactivity, and 3 (15% had mixed hypo- and hyperactivity. Repeat platelet aggregation studies were performed after a mean of 19 months (min: 5 months-max: 35 months in all patients who received imatinib mesylate during this period. After therapy, 18/20 (90% patients had abnormal laboratory results; 12 (60% had hypoactive platelets, 4 (20% had mixed hypo- and hyperactive platelets, and 2 (10% had hyperactive platelets. Three of the 8 patients with initial hypoactivity remained hypoactive, while 2 developed a mixed picture, 2 became hyperactive, and 1 normalized. Of the 6 patients with initial hyperactivity, 4 became hypoactive and 2 developed a mixed pattern. All of the 3 patients with initial hypo- and hyperactivity became hypoactive. Finally, 2 of the 3 patients with initial normal platelets became hypoactive while 1 remained normal. There was a significant decrease in ristocetin-induced platelet aggregation after therapy (p0.05. Conclusion: These findings indicate that a significant proportion of chronic myeloid leukemia patients have different patterns of platelet function abnormalities and imatinib mesylate has no effect on these abnormalities, with a significant impairment in ristocetin-induced platelet aggregation.

  2. Imatinib treatment causes substantial transcriptional changes in adult Schistosoma mansoni in vitro exhibiting pleiotropic effects.

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    Christin Buro

    2014-06-01

    Full Text Available Schistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ is the only drug widely used for controlling schistosomiasis. The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives. Studies on protein kinases (PKs demonstrated their importance for diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl-TK inhibitor used in human cancer therapy (Gleevec/Glivec. Imatinib exhibited dramatic effects on the morphology and physiology of adult schistosomes in vitro causing the death of the parasites.Here we show modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray analyses and qRT-PCR experiments were done to unravel transcriptional processes influenced by Imatinib in adult schistosomes in vitro demonstrating a wide influence on worm physiology. Surface-, muscle-, gut and gonad-associated processes were affected as evidenced by the differential transcription of e.g. the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of signaling genes including a ribosomal protein S6 kinase and a glutamate receptor. Finally, a comparative in silico analysis of the obtained microarray data sets and previous data analyzing the effect of a TGFβR1 inhibitor on transcription provided first evidence for an association of TGFβ and Abl kinase signaling. Among others GCP and egg formation-associated genes were identified as common targets.The data affirm broad negative effects of

  3. Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer trials with preoperative therapy: Literature-based meta-analysis.

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    Kataoka, K; Nakamura, K; Mizusawa, J; Kato, K; Eba, J; Katayama, H; Shibata, T; Fukuda, H

    2017-10-01

    There have been no reports evaluating progression-free survival (PFS) as a surrogate endpoint in resectable esophageal cancer. This study was conducted to evaluate the trial level correlations between PFS and overall survival (OS) in resectable esophageal cancer with preoperative therapy and to explore the potential benefit of PFS as a surrogate endpoint for OS. A systematic literature search of randomized trials with preoperative chemotherapy or preoperative chemoradiotherapy for esophageal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane Library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R 2 ) within PFS and OS. The primary analysis included trials in which the HR for both PFS and OS was reported. The sensitivity analysis included trials in which either HR or median survival time of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the median survival time of PFS and OS, assuming exponential distribution. Of 614 articles, 10 trials were selected for the primary analysis and 15 for the sensitivity analysis. The primary analysis did not show a correlation between treatment effects on PFS and OS (R 2 0.283, 95% CI [0.00-0.90]). The sensitivity analysis did not show an association between PFS and OS (R 2 0.084, 95% CI [0.00-0.70]). Although the number of randomized controlled trials evaluating preoperative therapy for esophageal cancer is limited at the moment, PFS is not suitable for primary endpoint as a surrogate endpoint for OS. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  4. Hepatectomized case of hepatocellular carcinoma after fast neutron irradiation therapy. A trial of the new preoperative treatment

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, Tohru; Ryu, Takamasa; Watanabe, Yoshiji

    1985-08-01

    A 51-year-old male patient with hepatocellular carcinoma was treated preoperatively by fast neutron radiotherapy (910 rad/7 fractions/15 days) with a field of 8 x 6 cm. Radiation-associated liver function disturbance was scarcely observed. No side effect, such as loss of appetite and general fatigue, was encountered. According to the classification of Ohoshi and Shimosato, histological effect of radiation was graded as II sub(A). There is no preoperative fast neutron radiotherapy for hepatocellular carcinoma in Japan in the literature.

  5. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

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    Yeo, Seung-Gu [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of); Oh, Jae Hwan [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Dae Yong, E-mail: radiopiakim@hanmail.net [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Lee, Jong Hoon; Jang, Hong Seok [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Kim, Jun-Gi [Department of Surgery, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Myung Ah [Department of Internal Medicine, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Nam, Taek-Keun [Department of Radiation Oncology, Chonnam National University Hospital, Gwang-Ju (Korea, Republic of)

    2013-05-01

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

  6. A Comparative Clinical Evaluation of the Effect of Preoperative and Postoperative Antimicrobial Therapy on Postoperative Sequelae after Impacted Mandibular Third Molar Extraction

    Directory of Open Access Journals (Sweden)

    Olurotimi Akanbi Olojede

    2014-07-01

    Full Text Available Objectives: To compare the effect of preoperative and postoperative antibiotics therapy on postoperative sequelae after impacted mandibular third molar extractions. Material and Methods: This was a prospective study conducted at Department of Oral and Maxillofacial Surgery of the Lagos University Teaching Hospitalon consecutive patients with impacted third molar extractions for a 12 month period. Group I (n = 31 had administration of 1 gram of oral metronidazole and 1 gram of amoxicillin capsules 30 minutes preoperative and Group II (n = 31 had 500 milligrams of amoxicillin capsule 8 hourly and 400 milligrams of metronidazole tablets administered post operatively for 5 days. Pain, facial swelling and mouth opening assessment were done postoperatively and on days 1, 3 and 7. Results: The general pattern of postoperative pain, regardless of antimicrobial use revealed that pain increased from day 1 to day 3 postoperatively and began to decrease in intensity subsequently up to the seventh day. There was however a statistically significant difference (P = 0.0001 between the two groups on the 7th postoperative day with the subjects in Group I showing lower pain intensity. The mean difference of the facial width on days 1 and 3 was significant (P = 0.04 and P = 0.0001 respectively with subjects in Group II having a reduced facial width compared to those in Group I. Conclusions: This study suggested that the administration of preoperative or postoperative antibiotics showed no marked differences in the degree of postoperative sequaele that occur after impacted mandibular third molar extractions.

  7. The effects of short-term preoperative physical therapy and education on early functional recovery of patients younger than 70 undergoing total hip arthroplasty

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    Vukomanović Aleksandra

    2008-01-01

    Full Text Available Background/Aim. Hip arthroplasty is a routine operation which relieves pain in patients with osteoarthritis. The role of physical therapy after hip arthroplasty was recognized, but the importance of preoperative physical therapy and education is still to be judged. The aim of this paper was to investigate the effect of short-term preoperative program of education and physical therapy on patients' early functional recovery immediately after total hip arthroplasty (THA. Methods. This prospective study included 45 patients with hip osteoarthritis scheduled to undergo primary THA and admitted to the Department of Orthopedics of Military Medical Academy. They were randomized into 2 groups: study and control one (with and without preoperative education and physical therapy. Preoperative education was conducted through conversation (1 appointment with physiatrist and brochure. The study group was instructed to perform exercises and basic activities from the postoperative rehabilitation program (2 practical classes with physiotherapist. Effects were measured with questionnaires (Harris, Oxford and Japanese Orthopaedic Association (JOA hip scores, range of motion and visual analog scale of pain. Marks showing ability to perform basic activities and endurance were from 0 (did not perform activity to 5 (independent and secure. Analyses examined differences between the groups over the preoperative and immediate postoperative periods and 15 months after the operation. Results. There were no differences between the groups at discharge according to pain, range of motion, Harris hip score and JOA hip score. Oxford hip score did not differ between the groups 15 months after the operation. The groups started to walk at the same time, but the study group walked up and down stairs (3.7±1.66 vs 5.37±1.46, p ≤ 0.002, used toilet (2.3±0.92 vs 3.2±1.24, p ≤ 0.02 and chair (2.2±1.01 vs 3.25±1.21, p ≤ 0.006 significantly earlier than the control group. On the

  8. Preoperative Concurrent Radiation Therapy and Chemotherapy for Bulky Stage IB2, IIA, and IIB Carcinoma of the Uterine Cervix With Proximal Parametrial Invasion

    International Nuclear Information System (INIS)

    Huguet, Florence; Cojocariu, Oana-Maria; Levy, Pierre; Lefranc, Jean-Pierre; Darai, Emile; Jannet, Denis; Ansquer, Yan; Lhuillier, Pierre-Eugene; Benifla, Jean-Louis; Seince, Nathalie; Touboul, Emmanuel

    2008-01-01

    Purpose: To evaluate toxicity, local tumor control, and survival after preoperative chemoradiation for operable bulky cervical carcinoma. Methods and Materials: Between December 1991 and July 2006, 92 patients with operable bulky stage IB2, IIA, and IIB cervical carcinoma without pelvic or para-aortic nodes on pretreatment imaging were treated. Treatment consisted of preoperative external beam pelvic radiation therapy (EBRT) and concomitant chemotherapy (CT) during the first and fourth weeks of radiation combining 5-fluorouracil and cisplatin. The pelvic radiation dose was 40.5 Gy over 4.5 weeks. EBRT was followed by low-dose rate uterovaginal brachytherapy with a total dose of 20 Gy in 62 patients. After a median rest period of 44 days, all patients underwent Class II modified radical hysterectomy with bilateral pelvic lymphadenectomy. Thirty patients who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy at a dose of 20 Gy. The mean follow-up was 46 months. Results: Pathologic residual tumor was observed in 43 patients. After multivariate analysis, additional preoperative uterovaginal brachytherapy was the single significant predictive factor for pathologic complete response rate (p = 0.019). The 2- and 5-year disease-free survival (DFS) rates were 80.4% and 72.2%, respectively. Pathologic residual cervical tumor was the single independent factor decreasing the probability of DFS (p = 0.020). Acute toxicities were moderate. Two severe ureteral complications requiring surgical intervention were observed. Conclusions: Concomitant chemoradiation followed by surgery for operable bulky stage I-II cervical carcinoma without clinical lymph node involvement can be used with acceptable toxicity. Pathologic complete response increases the probability of DFS

  9. Preoperative evaluation

    International Nuclear Information System (INIS)

    Murphy, C.H.; Murphy, M.R.

    1987-01-01

    The value of a preoperative chest radiograph is twofold. The examination may reveal unsuspected pathology that would alter the approach to surgery of anesthesia. Secondly, it provides a baseline or reference from which to evaluate subsequent post-operative films. The percentage of detection of unsuspected pathology on preoperative chest radiographs has been shown to be exceedingly small in certain patient populations. The authors do not recommend routine use of preoperative chest radiographs in children or in adults under the age of 40 who do not smoke, unless (1) the surgical disease has chest manifestations; (2) there is historic or clinical evidence of a coexisting disease with chest involvement; or (3) there is a likelihood that post-operative management will require follow-up films

  10. Imatinib-induced pleural effusion: A case report

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    R Banka

    2017-01-01

    Full Text Available Imatinib is a tyrosine kinase inhibitor and has rarely been reported to cause pleural effusion. We report the case of an 88-year-old male, known case of gastrointestinal stromal tumor on treatment with imatinib, who presented with a 2-week history of cough and dyspnea. He was diagnosed to have a right-sided pleural effusion and thoracentesis of the fluid revealed an exudate with low adenosine deaminase and negative cytology. Withdrawal of the drug lead to resolution of symptoms. We report this case to highlight the side effect profile of imatinib and warn physicians regarding this potential adverse effect which may be mistaken for metastasis or infection.

  11. Effect of combined treatment with preoperative. gamma. -therapy on function of gastrin producing cells in patients with gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Berdov, B A; Vedzizheva, T B; Bassalyk, L S; Zagrebin, V M [Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii; Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Nauchnyj Tsentr)

    1982-04-01

    It is stated that preoperative irradiation with the dose of 20 Gy doesn't produce any considerable effect on function of the extragastric gastrin producing cells. Despite the decrease of reserve potentialities of gastrin producing cells in patients with stomach cancer the basal level of gastrin in the group of gastric cancer patients on the whole is higher than in practically healthy people. Radiotherapy results in the pronounced inhiibition of gastrin synthesis and secretion of gastrin producing cells.

  12. Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial.

    Science.gov (United States)

    Cortes, Jorge E; Saglio, Giuseppe; Kantarjian, Hagop M; Baccarani, Michele; Mayer, Jiří; Boqué, Concepción; Shah, Neil P; Chuah, Charles; Casanova, Luis; Bradley-Garelik, Brigid; Manos, George; Hochhaus, Andreas

    2016-07-10

    We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib. Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms. These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long

  13. Impact of imatinib interruption and duration of prior hydroxyurea on the treatment outcome in patients with chronic myeloid leukemia: Single institution experience

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    Wael Abdelgawad Edesa

    2015-06-01

    Conclusion: Duration of prior hydroxyurea had no impact on response or progression free survival, while patients regular on imatinib had statistically significant difference with respect to major molecular response, complete molecular response and progression free survival compared to those who had periods of drug interruption, thus we need more governmental support to supply the drug without interruption to improve the outcome of therapy.

  14. Preoperative chemotherapy for operable breast cancer is associated with better compliance with adjuvant therapy in matched stage II and IIIA patients.

    Science.gov (United States)

    Komenaka, Ian K; Hsu, Chiu-Hsieh; Martinez, Maria Elena; Bouton, Marcia E; Low, Boo Ghee; Salganick, Jason A; Nodora, Jesse; Hibbard, Michael L; Jha, Chandra

    2011-01-01

    Preoperative chemotherapy (PC) for operable breast cancer has shown significant benefits in prospective trials. Many patients are treated in the community setting and some may question the applicability of PC outside the university setting. Retrospective review was performed of stage II and IIIA breast cancer patients treated from January 2002 to July 2009. Fifty-three of 57 patients who underwent PC were matched based on age, tumor size, and hormone receptor status with 53 patients who did not undergo PC. Differences in patient compliance with physician recommendations for all types of adjuvant therapy were evaluated. Crude odds ratios and adjusted odds ratios derived from conditional logistic regression models were calculated. There were 106 patients included. Patient compliance with chemotherapy was better in the PC group than in the adjuvant chemotherapy (AC) group (100% versus 70%; p = .0001). Similarly, more patients in the PC group completed radiation therapy (96% versus 65%; p = .0003) and initiated hormonal therapy (100% versus 62%; p = .0001). Conditional logistic regression revealed that higher pathologic stage and current cigarette smoking were associated with poorer compliance with chemotherapy. For radiation therapy, the univariate model revealed that compliance with chemotherapy and being employed were associated with completion of radiation, whereas current cigarette smoking and larger pathologic size were associated with poorer compliance with radiation. For hormonal therapy, current cigarette smokers were more likely to be noncompliant with initiation of hormonal therapy. PC for operable breast cancer can improve patient compliance with chemotherapy. Current cigarette smokers were more likely to be noncompliant with all types of adjuvant therapy.

  15. Regulation of HtrA2 on WT1 gene expression under imatinib stimulation and its effects on the cell biology of K562 cells.

    Science.gov (United States)

    Zhang, Lixia; Li, Yan; Li, Xiaoyan; Zhang, Qing; Qiu, Shaowei; Zhang, Qi; Wang, Min; Xing, Haiyan; Rao, Qing; Tian, Zheng; Tang, Kejing; Wang, Jianxiang; Mi, Yingchang

    2017-09-01

    The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis. Subsequent to treatment with drugs and UCF-101, the proliferative function of K562 cells was detected using MTT assays, and the rate of apoptosis was detected using Annexin V with propidium iodide flow cytometry in K562 cells. The protein levels in the signaling pathway were analyzed using western blotting following treatment with imatinib and UCF-101. In K562 cells, imatinib treatment activated HtrA2 gene at a transcription level, while the WT1 gene was simultaneously downregulated. Following HtrA2 inhibitor (UCF-101) treatment, the downregulation of WT1 increased gradually. At the protein level, imatinib induced the increase in HtrA2 protein level and concomitantly downregulated WT1 protein level. Subsequent to HtrA2 inhibition by UCF-101, the WT1 protein level decreased temporarily, but eventually increased. Imatinib induced apoptosis in K562 cells, but this effect was attenuated by the HtrA2 inhibitor UCF-101, resulting in the upregulation of the WT1 protein level. However; UCF-101 did not markedly change the proliferation inhibition caused by imatinib. Imatinib activated the p38 mitogen activated protein kinase (p38 MAPK) signaling pathway in K562 cells, and UCF-101 affected the activation of imatinib in the p38 MAPK signaling pathway. Imatinib inhibited the extracellular signal-related kinase (ERK1/2) pathway markedly and persistently, but UCF-101

  16. Clinical efficacy of second-generation tyrosine kinase inhibitors in imatinib-resistant gastrointestinal stromal tumors: a meta-analysis of recent clinical trials

    Directory of Open Access Journals (Sweden)

    Wu L

    2014-10-01

    Full Text Available Lile Wu, Zhongqiang Zhang, Hongliang Yao, Kuijie Liu, Yu Wen, Li Xiong Department of General Surgery, Second Xiangya Hospital of Central South University, Changsha, People's Republic of China Background: Primary and secondary resistance to imatinib, a selective receptor tyrosine kinase inhibitor (TKI, is a serious clinical problem in the control of advanced gastrointestinal stromal tumors (GIST. Here we report on a meta-analysis we performed to evaluate the efficacy of second-generation TKIs in the treatment of patients with imatinib-resistant GIST.Methods: Randomized controlled trials evaluating the clinical efficacy of second-generation TKIs were identified by searching PubMed and EMBASE from 2000 to February 2014. Outcomes subjected to analysis were progression-free survival and overall survival. Statistical analyses were performed using Review Manager version 5.1.0 (Cochrane Collaboration, Oxford, UK. Weighted hazard ratios (HR with 95% confidence intervals (CIs were calculated for the outcomes. Fixed-effects or random-effects models were used, depending on the degree of heterogeneity across the selected studies.Results: Three randomized controlled trials were selected for meta-analysis. Among imatinib-resistant or imatinib-intolerant patients, 541 received second-generation TKIs (sunitinib, nilotinib, or regorafenib and 267 controls received placebo or best supportive care. Progression-free survival was significantly improved in the TKI-treated group (HR 0.38; 95% CI 0.24–0.59; P<0.0001. No statistically significant difference was detected in overall survival between the treatment group and the control group (HR 0.85; 95% CI 0.71–1.03; P=0.09. In the subgroup of patients who were resistant or intolerant to both imatinib and sunitinib, TKI therapy (nilotinib or regorafenib improved progression-free survival (HR 0.40; 95% CI 0.19–0.84; P=0.02 but not overall survival (HR 0.83; 95% CI 0.63–1.08; P=0.17. Regorafenib was shown to be

  17. Randomized controlled trial of perioperative antimicrobial therapy based on the results of preoperative bile cultures in patients undergoing biliary reconstruction.

    Science.gov (United States)

    Okamura, Kunishige; Tanaka, Kimitaka; Miura, Takumi; Nakanishi, Yoshitsugu; Noji, Takehiro; Nakamura, Toru; Tsuchikawa, Takahiro; Okamura, Keisuke; Shichinohe, Toshiaki; Hirano, Satoshi

    2017-07-01

    The high frequency of surgical site infections (SSIs) after hepato-pancreato-biliary (HPB) surgery is a problem that needs to be addressed. This prospective, randomized, controlled study examined whether perioperative prophylactic use of antibiotics based on preoperative bile culture results in HPB surgery could decrease SSI. Participants comprised 126 patients who underwent HPB (bile duct, gallbladder, ampullary, or pancreatic) cancer surgery with biliary reconstruction at Hokkaido University Hospital between August 2008 and March 2013 (UMIN Clinical Trial Registry #00001278). Before surgery, subjects were randomly allocated to a targeted group administered antibiotics based on bile culture results or a standard group administered cefmetazole. The primary endpoint was SSI rates within 30 days after surgery. Secondary endpoint was SSI rates for each operative procedure. Of the 126 patients, 124 were randomly allocated (targeted group, n = 62; standard group, n = 62). Frequency of SSI after surgery was significantly lower in the targeted group (27 patients, 43.5%) than in the standard group (44 patients, 71.0%; P = 0.002). Among patients who underwent pancreaticoduodenectomy and hepatectomy, SSI occurred significantly less frequently in the targeted group (P = 0.001 and P = 0.025, respectively). This study demonstrated that preoperative bile culture-targeted administration of prophylactic antibiotics decreased SSIs following HBP surgery with biliary reconstruction. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  18. Imatinib for the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumours: systematic review and economic evaluation.

    Science.gov (United States)

    Wilson, J; Connock, M; Song, F; Yao, G; Fry-Smith, A; Raftery, J; Peake, D

    2005-07-01

    To assess the clinical and cost-effectiveness of imatinib in the treatment of unresectable and/or metastatic, KIT-positive, gastrointestinal stromal tumours (GISTs), relative to current standard treatments. Electronic databases. As there were no randomised trials that have directly compared imatinib with the current standard treatment in patients with advanced GIST, this review included non-randomised controlled studies, cohort studies, and case series that reported effectiveness results of treatment with imatinib and/or other interventions in patients with advanced GIST. The effectiveness assessment was based on the comparison of results from imatinib trials and results from studies of historical control patients. Economic evaluation was mainly based on an assessment and modification (when judged necessary) of a model submitted by Novartis. Evidence from published uncontrolled trials involving 187 patients, and from abstracts reporting similar uncontrolled trials involving 1700 patients, indicates that approximately 50% of imatinib-treated individuals with advanced GIST experience a dramatic clinical response in terms of at least a 50% reduction in tumour mass. At present, although useful data are accumulating, it is not possible to predict which patients may respond in this way. Fifteen studies where possible GIST patients had been treated with therapies other than imatinib or best supportive care were also identified. All imatinib-treated patients experienced adverse effects, although they were relatively mild. Overall, imatinib was reported to be well tolerated. The most common serious events included unspecified haemorrhage and neutropenia. Skin rash, oedema and periorbital oedema were the common adverse events observed. Patients on the highest dose regimen (1000 mg per day in one trial) may experience dose-limiting drug toxicity. A structured assessment was carried out of the Novartis economic evaluation of imatinib for unresectable and/or metastatic GIST

  19. MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer.

    Science.gov (United States)

    Momose, Kota; Yamasaki, Makoto; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2017-07-01

    Programmed death-ligand 1 (PD-1/PD-L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD-L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair-deficient tumors are associated with improved survival, although they are not sensitive to 5-fluorouracil-based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD-L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD-L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD-L1 expression. The 5-year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (PMLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD-L1 expression.

  20. The Impact of a Preoperative Cognitive Behavioural Therapy (CBT) on Dysfunctional Eating Behaviours, Affective Symptoms and Body Weight 1 Year after Bariatric Surgery: A Randomised Controlled Trial.

    Science.gov (United States)

    Gade, Hege; Friborg, Oddgeir; Rosenvinge, Jan H; Småstuen, Milada Cvancarova; Hjelmesæth, Jøran

    2015-11-01

    To examine whether a preoperative cognitive behavioural therapy (CBT) intervention exceeds usual care in the improvements of dysfunctional eating behaviours, mood, affective symptoms and body weight 1 year after bariatric surgery. This is a 1-year follow-up of a single centre parallel-group randomised controlled trial ( http://clinicaltrials.gov/ct2/show/NCT01403558). A total of 80 (55 females) patients mean (SD) age 44 (10) years were included. The intervention group received 10 weeks of CBT prior to bariatric surgery, and the control group received nutritional support and education. Both groups were assessed at baseline (T0), post CBT intervention/preoperatively (T1), and 1 year postoperatively (T2). Using a mixed modelling statistical approach, we examined if the CBT group improved more across time than the control group. Our hypothesis was not supported as both groups had comparable improvements in all outcomes except for anxiety symptoms. Body weight declined by 30.2 % (37.3 kg) in the CBT group and by 31.2 % (40.0 kg) in the control group from baseline to follow-up, p = 0.82. There were statistically significant reductions in anxiety and depression symptoms in the CBT group between T0 and T1 and between T1 and T2 for depression only. However, in the control group, the anxiety score did not change significantly. The CBT group showed an earlier onset of improvements in all eating behaviours and affective symptoms than the control group. The 10-week CBT intervention showed beneficial effects preoperatively, but the non-significant group differences postoperatively indicate a genuine effect of surgery.

  1. The effect of preoperative therapy against advanced oral cancer. The pattern of residual cancer nests assessed with semiserial whole surgical specimens

    International Nuclear Information System (INIS)

    Kawano, Kenji

    2008-01-01

    Histological change of advanced oral cancers following concurrent chemoradiotherapy was examined with semiserial whole surgical specimens. Subjects included six tongue squamous cell carcinomas (SCCs), two oral floor SCCs and three lower gingival SCCs, and all the tumors were preoperatively treated by the combination of radiotherapy and superselective intraarterial infusion of carboplatin (CBDCA) or oral administration of TS-1. Clinical effect was assessed as complete response (CR) in three cases, partial response (PR) in five, minor response (MR) in two and no change (NC) in two. The distribution of residual cancer nests was categorized as the superficially-located and deeply-located patterns. It was noteworthy that the pattern of residual cancer nests and the histological effect were different between sections even in the same tumors. Furthermore, a few viable cancer nests were observed exclusively in the advancing edge in tumors assessed as Grade 2b (Oboshi-Shimosata classification), where most of the cancer nests were degenerative or necrotic. This finding suggests that the extent of resection could not be reduced even in tumors that responded well to preoperative therapy. In the present cases, the histological effect of chemoradiotherapy was evaluated as Grade 4a in two cases, Grade 2b in four, Grade 2a in five and Grade 1 in one. Tumors of the PR showed a wide variation of histological evaluation from Grade 1 to Grade 4a, resulting in a discrepancy between the clinical and histological evaluations. (author)

  2. Effects of preoperative aspirin and clopidogrel therapy on perioperative blood loss and blood transfusion requirements in patients undergoing off-pump coronary artery bypass graft surgery.

    Science.gov (United States)

    Shim, Jae Kwang; Choi, Yong Seon; Oh, Young Jun; Bang, Sou Ouk; Yoo, Kyung Jong; Kwak, Young Lan

    2007-07-01

    Preoperative exposure to clopidogrel and aspirin significantly increases postoperative bleeding in patients undergoing on-pump coronary artery bypass graft surgery. Off-pump coronary bypass grafting has been proposed as an alternative technique to attenuate postoperative bleeding associated with clopidogrel. This study aimed to determine the effects of aspirin and clopidogrel therapy on perioperative blood loss and blood transfusion requirements in off-pump coronary artery bypass grafting. One hundred six patients scheduled for off-pump coronary artery bypass grafting were divided into three groups: aspirin and clopidogrel discontinued more than 6 days before surgery (group 1, n = 35), aspirin and clopidogrel continued until 3 to 5 days before surgery (group 2, n = 51), and both medications continued within 2 days of surgery (group 3, n = 20). Thromboelastographic tracings were analyzed before induction of anesthesia. Routine coagulation profiles were measured before and after surgery. A cell salvage device was used during surgery and salvaged blood was reinfused. Chest tube drainage and blood transfusion requirement were recorded postoperatively. Patient characteristics, operative data, and thromboelastographic tracings were similar among the groups. There were significant decreases in hematocrit level and platelet count and prolongation in prothrombin time postoperatively in all groups without any intergroup differences. The amounts of perioperative blood loss and blood transfusion required were all similar among the groups. Preoperative clopidogrel and aspirin exposure even within 2 days of surgery does not increase perioperative blood loss and blood transfusion requirements in patients undergoing elective off-pump coronary artery bypass grafting.

  3. Role of preoperative intravenous iron therapy to correct anemia before major surgery: study protocol for systematic review and meta-analysis.

    Science.gov (United States)

    Elhenawy, Abdelsalam M; Meyer, Steven R; Bagshaw, Sean M; MacArthur, Roderick G; Carroll, Linda J

    2015-03-15

    Preoperative anemia is a common and potentially serious hematological problem in elective surgery and increases the risk for perioperative red blood cell (RBC) transfusion. Transfusion is associated with postoperative morbidity and mortality. Preoperative intravenous (IV) iron therapy has been proposed as an intervention to reduce perioperative transfusion; however, studies are generally small, limited, and inconclusive. We propose performing a systematic review and meta-analysis. We will search MEDLINE, EMBASE, EBM Reviews, Cochrane-controlled trial registry, Scopus, registries of health technology assessment and clinical trials, Web of Science, ProQuest Dissertations and Theses, and conference proceedings in transfusion, hematology, and surgery. We will contact our study drug manufacturer for unpublished trials. Titles and abstracts will be identified and assessed by two reviewers for potential relevance. Eligible studies are: randomized or quasi-randomized clinical trials comparing preoperative administration of IV iron with placebo or standard of care to reduce perioperative blood transfusion in anemic patients undergoing major surgery. Screening, data extraction, and quality appraisal will be conducted independently by two authors. Data will be presented in evidence tables and in meta-analytic forest plots. Primary efficacy outcomes are change in hemoglobin concentration and proportion of patients requiring RBC transfusion. Secondary outcomes include number of units of blood or blood products transfused perioperatively, transfusion-related acute lung injury, neurologic complications, adverse events, postoperative infections, cardiopulmonary complications, intensive care unit (ICU) admission/readmission, length of hospital stay, acute kidney injury, and mortality. Dichotomous outcomes will be reported as pooled relative risks and 95% confidence intervals. Continuous outcomes will be reported using calculated weighted mean differences. Meta-regression will be

  4. A combination therapy with preoperative full-dose gemcitabine, concurrent 3-dimensional conformal radiation, surgery and postoperative liver perfusion chemotherapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Ohigashi, Hiroaki; Eguchi, Hidetoshi; Takahashi, Hidenori

    2009-01-01

    Due to the high incidence of local recurrence and liver metastasis, long-term outcomes for patients after resection of pancreatic cancer are extremely poor. For improving the survival of the patients, a combination of preoperative chemoradiation, surgery, and postoperative liver-perfusion chemotherapy (LPC) were performed. Postoperative histopathologic study revealed a marked degenerative change in cancer tissue, showing negative surgical margins (R0) in 98% of patients and negative nodal involvement in 85% of patients. The 5-year survival rate after pancreatectomy was 56%, with low incidences of both local recurrence (11%) and liver metastasis (9%). This combination therapy were able to effectively reduce the incidence of both local and liver recurrence and improved long-term outcomes for patients with T3-4 cancers of the pancreas. (author)

  5. A feasibility randomised controlled trial of pre-operative occupational therapy to optimise recovery for patients undergoing primary total hip replacement for osteoarthritis (PROOF-THR).

    Science.gov (United States)

    Jepson, Paul; Sands, Gina; Beswick, Andrew D; Davis, Edward T; Blom, Ashley W; Sackley, Catherine M

    2016-02-01

    To assess the feasibility of a pre-operative occupational therapy intervention for patients undergoing primary total hip replacement. Single blinded feasibility randomised controlled trial, with data collection prior to the intervention, and at 4, 12, and 26 weeks following surgery. Recruitment from two NHS orthopaedic outpatient centres in the West Midlands, UK. Patients awaiting primary total hip replacement due to osteoarthritis were recruited. Following pre-operative assessment, patients were individually randomised to intervention or control by a computer-generated block randomisation algorithm stratified by age and centre. The intervention group received a pre-surgery home visit by an occupational therapist who discussed expectations, assessed home safety, and provided appropriate adaptive equipment. The control group received treatment as usual. The study assessed the feasibility of recruitment procedures, delivery of the intervention, appropriateness of outcome measures and data collection methods. Health related quality of life and resource use were recorded at 4, 12 and 26 weeks. Forty-four participants were recruited, 21 were randomised to the occupational therapy intervention and 23 to usual care. Analysis of 26 week data included 18 participants in the intervention group and 21 in the control. The intervention was delivered successfully with no withdrawals or crossovers; 5/44 were lost to follow-up with further missing data for participation and resource use. The feasibility study provided the information required to conduct a definitive trial. Burden of assessment would need to be addressed. A total of 219 patients would be required in an efficacy trial. © The Author(s) 2015.

  6. A clinical study of postoperative changes in immunity of patients with digestive organ cancers and effectiveness of oriental medicine in esophageal cancer preoperative irradiation therapy

    International Nuclear Information System (INIS)

    Yamada, Teruji

    1993-01-01

    In esophageal cancer, the operative stress caused by thoracotomy and laparotomy is great and, postoperatively, immunity suppressive conditions are seen. Again, it is a known fact that when irradiation is applied pre- and postoperatively, the immunity aptitude will drop even further. Experimentally, Juzen-taiho-to is an oriental medicine reported as having immunity suppressive preventive effects. Juzen-taiho-to is also reported as effective in decreasing side effects caused by anti-cancer agents. However, detailed reports on administration effects of Juzen-taiho-to against irradiation therapy for esophageal cancer has yet to be seen. This time, studies were made on the administration effects of Juzen-taiho-to in esophageal cancer. The subjects of examination were 21 cases in which preoperative irradiation therapy and curative resection was made. Also, 46 cases of non-irradiation therapy and curative resection were studied. These cases were divided into two groups: the Juzen-taiho-to dosaged group (JT), and the non-dosaged (controlled) group (NJT). The hemoglobin value in the irradiated and non-irradiated group did not display apparent differences in both the JT group and the NJT group. In blood serum albumin value, at one month postoperatively, an improvement trend was seen in the JT group as opposed to the NJT group. (author)

  7. Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report

    International Nuclear Information System (INIS)

    Florczynski, Matthew M.; Sanatani, Michael S.; Mai, Lauren; Fisher, Barbara; Moulin, Dwight E.; Cao, Jeffrey; Louie, Alexander V.; Pope, Janet E.; Leung, Eric

    2016-01-01

    The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemotherapy. We report a case of a patient who developed a debilitating bilateral myopathy of the hip flexors after successful treatment for rectal cancer. To the best of our knowledge, this is the first such complication from radiation therapy reported in a patient with colorectal cancer. The disproportionate severity of our patient’s myopathy relative to the dose of radiation used also makes this case unique among reports of neuromuscular complications from radiation therapy. The patient is a 65-year-old male with node negative, high-grade adenocarcinoma of the rectum penetrating through the distal rectal wall. He underwent neoadjuvant concurrent pelvic radiation therapy and capecitabine-based chemotherapy, followed by abdominoperineal resection and post-operative FOLFOX chemotherapy. Five months post-completion of pelvic radiotherapy and 2 months after the completion of adjuvant chemotherapy, he presented with bilateral weakness of the iliopsoas muscles and severe pain radiating to the groin. The patient improved with 40 mg/d of prednisone, which was gradually tapered to 2 mg/d over 6 months, with substantial recovery of muscle strength and elimination of pain. The timing, presentation and response of our patient’s symptoms to corticosteroids are most consistent with a radiation recall reaction. Radiation recall is a phenomenon whereby previously irradiated tissue becomes vulnerable to toxicity by subsequent systemic therapy and is rarely associated with myopathies. Radiation recall should be considered a potential complication of neoadjuvant radiation therapy for rectal cancer, and for ongoing research into the optimization of treatment for these patients. Severe myopathies caused by radiation recall may be fully reversible with corticosteroid treatment

  8. Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report.

    Science.gov (United States)

    Florczynski, Matthew M; Sanatani, Michael S; Mai, Lauren; Fisher, Barbara; Moulin, Dwight E; Cao, Jeffrey; Louie, Alexander V; Pope, Janet E; Leung, Eric

    2016-03-22

    The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemotherapy. We report a case of a patient who developed a debilitating bilateral myopathy of the hip flexors after successful treatment for rectal cancer. To the best of our knowledge, this is the first such complication from radiation therapy reported in a patient with colorectal cancer. The disproportionate severity of our patient's myopathy relative to the dose of radiation used also makes this case unique among reports of neuromuscular complications from radiation therapy. The patient is a 65-year-old male with node negative, high-grade adenocarcinoma of the rectum penetrating through the distal rectal wall. He underwent neoadjuvant concurrent pelvic radiation therapy and capecitabine-based chemotherapy, followed by abdominoperineal resection and post-operative FOLFOX chemotherapy. Five months post-completion of pelvic radiotherapy and 2 months after the completion of adjuvant chemotherapy, he presented with bilateral weakness of the iliopsoas muscles and severe pain radiating to the groin. The patient improved with 40 mg/d of prednisone, which was gradually tapered to 2 mg/d over 6 months, with substantial recovery of muscle strength and elimination of pain. The timing, presentation and response of our patient's symptoms to corticosteroids are most consistent with a radiation recall reaction. Radiation recall is a phenomenon whereby previously irradiated tissue becomes vulnerable to toxicity by subsequent systemic therapy and is rarely associated with myopathies. Radiation recall should be considered a potential complication of neoadjuvant radiation therapy for rectal cancer, and for ongoing research into the optimization of treatment for these patients. Severe myopathies caused by radiation recall may be fully reversible with corticosteroid treatment.

  9. Effect of imatinib on growth of experimental endometriosis in rats.

    Science.gov (United States)

    Yildiz, Caglar; Kacan, Turgut; Akkar, Ozlem Bozoklu; Karakus, Savas; Seker, Metin; Kacan, Selen Baloglu; Ozer, Hatice; Cetin, Ali

    2016-02-01

    Currently, medical and surgical treatment options for endometriosis are limited due to suboptimal efficacy, and also safety and tolerance issues. Long-term use of gonadotrophin-releasing hormone analogs, androgenes, and the danazol, which are widely used drugs for endometriosis, is usually not possible due to their suboptimal safety and tolerance profile. The lack of an effective, tolerable and safe treatment option for endometriosis makes animal models of experimental endometriosis necessary to study candidate drugs. The aim of this study was to investigate the efficacy of imatinib on the experimental endometriosis in a rat model. Endometriosis was induced by autotransplantation of uterine tissue into the peritoneal cavity. Twenty-four rats, which had visually confirmed endometriotic implants on subsequent laparotomy, were randomized into three groups to receive imatinib (25mg/kg/day, p.o.), anastrozole (0.004 mg/day, p.o.), or normal saline (0.1 mL, i.p.) for 14 days. After removal of endometriotic tissue and H & E staining, endometriosis score was determined according to a semiquantitative histological classification. Also, immunostaining with primary antibodies including VEGF, CD117, and Bax were used for immunohistochemical (IHC) examination. Both anastrozole and imatinib suppressed the growth of endometriotic tissue and reduced the number of ovarian follicles. Although the difference was not statistically significant, imatinib was less effective than anastrozole for treatment of endometriosis. Imatinib effectively treats experimental endometriosis by its inhibitor effects on angiogenesis and cell proliferation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    But-Hadzic, Jasna, E-mail: jbut@onko-i.si [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Anderluh, Franc [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Brecelj, Erik; Edhemovic, Ibrahim [Division of Surgery, Institute of Oncology, Ljubljana (Slovenia); Secerov-Ermenc, Ajra; Hudej, Rihard; Jeromen, Ana [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Kozelj, Miran; Krebs, Bojan [Division of Surgery, University Medical Centre Maribor, Maribor (Slovenia); Oblak, Irena [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Omejc, Mirko [Division of Surgery, University Medical Centre Lubljana, Ljubljana (Slovenia); Vogrin, Andrej [Division of Diagnostics, Institute of Oncology, Ljubljana (Slovenia); Velenik, Vaneja [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia)

    2016-12-01

    Background and Purpose: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Methods and Materials: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m{sup 2}/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Results: Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Conclusions: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.

  11. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia.

    Science.gov (United States)

    Darkow, Theodore; Henk, Henry J; Thomas, Simu K; Feng, Weiwei; Baladi, Jean-Francois; Goldberg, George A; Hatfield, Alan; Cortes, Jorge

    2007-01-01

    patients resumed imatinib within the study period. In this population, MPR decreased as the number of concomitant medications increased (p = 0.002), and was lower among women (p = 0.003), patients with high cancer complexity (p = 0.003) and patients with a higher starting dose of imatinib (p = 0.04). Women were approximately twice as likely as men to have a treatment interruption (p = 0.009), as were patients with a high cancer complexity (p = 0.03). After adjusting for the aforementioned covariates, MPR was found to be inversely associated with healthcare costs excluding imatinib (p < 0.001) and medical costs (p < 0.001). A 10% point difference in MPR was associated with a 14% difference in healthcare costs excluding imatinib and a 15% difference in medical costs. For example, patients with an MPR of 75% incur an additional 4072 US dollars in medical costs annually compared with patients with an MPR of 85%. Treatment interruptions and non-adherence with imatinib, both of which could lead to undesired clinical and economic outcomes, appear to be prevalent. Physicians and pharmacists should educate patients and closely monitor adherence to therapy, as improving adherence and limiting treatment interruptions may not only optimise clinical outcomes but also reduce the economic burden of CML.

  12. Results of preoperative combined therapy with radiation and multi-drug chemotherapy for oral squamous cell carcinomas

    International Nuclear Information System (INIS)

    Iwai, Masayuki; Sawada, Toshiharu; Furuta, Isao; Sado, Tadashi; Terashima, Ryuichi; Ito, Shigeto

    1996-01-01

    We retrospectively analyzed the effectiveness of preoperative treatment with combined chemotherapy, including cisplatin (CDDP) and carboplatin (CBDCA), and radiotherapy. Among 19 patients with oral squamous cell carcinoma, the primary site was the tongue in 13, the oral floor in 3, and the maxilla, lip, and gingiva in 1 case each. The clinical stage was 7 cases Stage II, 5 cases Stage III, and 7 cases Stage IV. Chemotherapy was administered intravenously using CDDP 50-80 mg (1 time) or CBDCA 150 mg once a week in a total dose of 300-750 mg, PEP 5 mg twice a week in a total dose of 40-60 mg, and 5-FU or Tegaful 300-600 mg in a total dose of 9.0-18.0 g. Radiotherapy was carried out with Lineac (5 times a week) in a total dose of 20-40 Gy/10-20 f/10-20 days. The clinical response to treatment was evaluated as CR 3 cases, PR 9 cases, and NC 6 cases. The response rate was 12/18 (66.7%) cases. Histologic effectiveness, evaluated according to the classification of Oohoshi and Shimosato, was Grade IV 11 cases, Grade III 3 cases, and Grade II 5 cases. The following adverse reactions were reported: stomatitis 19 cases, fever 13 cases, leukopenia 12 cases, loss of appetite 12 cases, and neutropenia 10 cases. Fourteen of the 19 patients (73.7%) have a good prognosis, without any signs of recurrence or metastasis. The results indicate that multidrug chemotherapy combined with radiotherapy is effective even for highly malignant carcinoma in the oral cavity. (author)

  13. Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Conradi, Lena [Department of General Surgery, University Medical Center of Göttingen (Germany); Weiss, Christian [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Sprenger, Thilo [Department of General Surgery, University Medical Center of Göttingen (Germany); Middel, Peter [Institute for Pathology, University Medical Center, Göttingen (Germany); Rau, Tillman [Institute of Pathology, University Hospital Erlangen, Erlangen (Germany); Dellas, Kathrin [Department of Radiotherapy, Lübeck University (Germany); Kitz, Julia [Institute for Pathology, University Medical Center, Göttingen (Germany); Rödel, Franz [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Sauer, Rolf [Department of Radiation Oncology, University of Erlangen (Germany); Rüschoff, Josef [Targos Molecular Pathology, Kassel (Germany); Beissbarth, Tim [Department of Medical Statistics, University Medical Center of Göttingen (Germany); Arnold, Dirk [Tumor Biology Center Freiburg, University of Freiburg (Germany); Ghadimi, B. Michael [Department of General Surgery, University Medical Center of Göttingen (Germany); Rödel, Claus [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Liersch, Torsten [Department of General Surgery, University Medical Center of Göttingen (Germany)

    2013-12-01

    Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not

  14. Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

    International Nuclear Information System (INIS)

    Fokas, Emmanouil; Conradi, Lena; Weiss, Christian; Sprenger, Thilo; Middel, Peter; Rau, Tillman; Dellas, Kathrin; Kitz, Julia; Rödel, Franz; Sauer, Rolf; Rüschoff, Josef; Beissbarth, Tim; Arnold, Dirk; Ghadimi, B. Michael; Rödel, Claus; Liersch, Torsten

    2013-01-01

    Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not

  15. SU-E-T-311: Dosimetric Comparison of Volumetric Modulated Arc Therapy Plans for Preoperative Radiotherapy Rectal Cancer Using Flattening Filter-Free and Flattening Filter Modes

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, W; Zhang, J; Lu, J; Chen, C [Cancer Hospital of Shantou University Medical College, Shantou, Guangdong (China)

    2015-06-15

    Purpose: To compare the dosimetric difference of volumetric modulated arc therapy(VMAT) for preoperative radiotherapy rectal cancer using 6MV X-ray flattening filter free(FFF) and flattening filter(FF) modes. Methods: FF-VMAT and FFF-VMAT plans were designed to 15 rectal cancer patients with preoperative radiotherapy by planning treatment system(Eclipse 10.0),respectively. Dose prescription was 50 Gy in 25 fractions. All plans were normalized to 50 Gy to 95% of PTV. The Dose Volume Histogram (DVH), target and risk organ doses, conformity indexes (CI), homogeneity indexes (HI), low dose volume of normal tissue(BP), monitor units(MU) and treatment time (TT) were compared between the two kinds of plans. Results: FF-VMAT provided the lower Dmean, V105, HI, and higher CI as compared with FFF-VMAT. The small intestine of D5, Bladder of D5, Dmean, V40, V50, L-femoral head of V40, R-femoral head of Dmean were lower in FF-VMAT than in FFF-VMAT. FF-VMAT had higher BP of V5, but no significantly different of V10, V15, V20, V30 as compared with FFF-VMAT. FF-VMAT reduceed the monitor units(MU) by 21%(P<0.05), as well as the treatment time(TT) was no significantly different(P>0.05), as compared with FFF-VMAT. Conclusion: The plan qualities of FF and FFF VMAT plans were comparable and both clinically acceptable. FF-VMAT as compared with FFF-VMAT, showing better target coverage, some of OARs sparing, the MUs of FFF-VMAT were higher than FF-VMAT, yet were delivered within the same time. This work was supported by the Medical Scientific Research Foundation of Guangdong Procvince (A2014455 to Changchun Ma)

  16. Dosimetric feasibility of magnetic resonance imaging-guided tri-cobalt 60 preoperative intensity modulated radiation therapy for soft tissue sarcomas of the extremity.

    Science.gov (United States)

    Kishan, Amar U; Cao, Minsong; Mikaeilian, Argin G; Low, Daniel A; Kupelian, Patrick A; Steinberg, Michael L; Kamrava, Mitchell

    2015-01-01

    The purpose of this study was to investigate the dosimetric differences of delivering preoperative intensity modulated radiation therapy (IMRT) to patients with soft tissue sarcomas of the extremity (ESTS) with a teletherapy system equipped with 3 rotating (60)Co sources and a built-in magnetic resonance imaging and with standard linear accelerator (LINAC)-based IMRT. The primary study population consisted of 9 patients treated with preoperative radiation for ESTS between 2008 and 2014 with LINAC-based static field IMRT. LINAC plans were designed to deliver 50 Gy in 25 fractions to 95% of the planning target volume (PTV). Tri-(60)Co system IMRT plans were designed with ViewRay system software. Tri-(60)Co-based IMRT plans achieved equivalent target coverage and dosimetry for organs at risk (long bone, skin, and skin corridor) compared with LINAC-based IMRT plans. The maximum and minimum PTV doses, heterogeneity indices, and ratio of the dose to 50% of the volume were equivalent for both planning systems. One LINAC plan violated the maximum bone dose constraint, whereas none of the tri-(60)Co plans did. Using a tri-(60)Co system, we were able to achieve equivalent dosimetry to the PTV and organs at risk for patients with ESTS compared with LINAC-based IMRT plans. The tri-(60)Co system may be advantageous over current treatment platforms by allowing PTV reduction and by elimination of the additional radiation dose associated with daily image guidance, but this needs to be evaluated prospectively. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  17. Effect of preoperative ibuprofen in controlling postendodontic pain with and without low-level laser therapy in single visit endodontics: A randomized clinical study

    Directory of Open Access Journals (Sweden)

    Shahnaz Nabi

    2018-01-01

    Full Text Available Aim: The aim of this study is to evaluate the effect of low-level laser irradiation and ibuprofen in reducing the onset and severity of postoperative pain following single visit endodontics. Materials and Methods: One hundred and twenty patients were recruited for this study. Group A (n = 30 patients were administered 400 mg of ibuprofen orally 1 h before the institution of an endodontic procedure. Group B (n = 30 patients were given irradiation of a low-level laser at 50 Hz for 3 min after the standard endodontic procedure at the periapical region on both buccal and lingual aspect. Group C (n = 30 patients were given preoperative ibuprofen followed with a low-level laser at 50 Hz for 3 min after endodontic treatment. Group D (n = 30 patients were administered no preoperative ibuprofen nor low-level laser irradiation after the endodontic procedure. The patient immediately recorded his/her pain perception on the Heft Parker pain survey after completion of the appointment and at 4, 8, 12, 24, and 48 h postoperatively. Inter group analysis was carried out using the analysis of variances with “least significant difference” post hoc test. For intra group analysis, Student's t-test was used. Chi-square test was applied for nonparametric data. Results: Pain was significantly reduced in all the treatment groups postoperatively. Ibuprofen showed significant pain reduction at 4 h and 8 h period. The combination of low-level laser and ibuprofen showed the best results in terms of postoperative pain reduction. Conclusion: This study proved that low-level laser therapy can be an effective alternative for conventional use of nonsteroidal anti-inflammatory drugs in controlling postendodontic pain thereby eliminating the adverse effects of such drugs on the patients.

  18. Bioinspired co-crystals of Imatinib providing enhanced kinetic solubility.

    Science.gov (United States)

    Reggane, Maude; Wiest, Johannes; Saedtler, Marco; Harlacher, Cornelius; Gutmann, Marcus; Zottnick, Sven H; Piechon, Philippe; Dix, Ina; Müller-Buschbaum, Klaus; Holzgrabe, Ulrike; Meinel, Lorenz; Galli, Bruno

    2018-05-04

    Realizing the full potential of co-crystals enhanced kinetic solubility demands a comprehensive understanding of the mechanisms of dissolution, phase conversion, nucleation and crystal growth, and of the complex interplay between the active pharmaceutical ingredient (API), the coformer and co-existing forms in aqueous media. One blueprint provided by nature to keep poorly water-soluble bases in solution is the complexation with phenolic acids. Consequently, we followed a bioinspired strategy for the engineering of co-crystals of a poorly water-soluble molecule - Imatinib - with a phenolic acid, syringic acid (SYA). The dynamics of dissolution and solution-mediated phase transformations were monitored by Nuclear Magnetic Resonance (NMR) spectroscopy, providing mechanistic insights into the 60 fold-increased long lasting concentrations achieved by the syringate co-crystals as compared to Imatinib base and Imatinib mesylate. This lasting effect was linked to SYA's ability to delay the formation and nucleation of Imatinib hydrate - the thermodynamically stable form in aqueous media - through a metastable association of SYA with Imatinib in solution. Results from permeability studies evidenced that SYA did not impact Imatinib's permeability across membranes while suggesting improved bioavailability through higher kinetic solubility at the biological barriers. These results reflect that some degree of hydrophobicity of the coformer might be key to extend the kinetic solubility of co-crystals with hydrophobic APIs. Understanding how kinetic supersaturation can be shaped by the selection of an interactive coformer may help achieving the needed performance of new forms of poorly water-soluble, slowly dissolving APIs. Copyright © 2018. Published by Elsevier B.V.

  19. In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells

    International Nuclear Information System (INIS)

    Weigel, Marion T; Maass, Nicolai; Mundhenke, Christoph; Dahmke, Linda; Schem, Christian; Bauerschlag, Dirk O; Weber, Katrin; Niehoff, Peter; Bauer, Maret; Strauss, Alexander; Jonat, Walter

    2010-01-01

    Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction. Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin. The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment. Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer

  20. Exploiting mitochondrial dysfunction for effective elimination of imatinib-resistant leukemic cells.

    Directory of Open Access Journals (Sweden)

    Jérome Kluza

    Full Text Available Challenges today concern chronic myeloid leukemia (CML patients resistant to imatinib. There is growing evidence that imatinib-resistant leukemic cells present abnormal glucose metabolism but the impact on mitochondria has been neglected. Our work aimed to better understand and exploit the metabolic alterations of imatinib-resistant leukemic cells. Imatinib-resistant cells presented high glycolysis as compared to sensitive cells. Consistently, expression of key glycolytic enzymes, at least partly mediated by HIF-1α, was modified in imatinib-resistant cells suggesting that imatinib-resistant cells uncouple glycolytic flux from pyruvate oxidation. Interestingly, mitochondria of imatinib-resistant cells exhibited accumulation of TCA cycle intermediates, increased NADH and low oxygen consumption. These mitochondrial alterations due to the partial failure of ETC were further confirmed in leukemic cells isolated from some imatinib-resistant CML patients. As a consequence, mitochondria generated more ROS than those of imatinib-sensitive cells. This, in turn, resulted in increased death of imatinib-resistant leukemic cells following in vitro or in vivo treatment with the pro-oxidants, PEITC and Trisenox, in a syngeneic mouse tumor model. Conversely, inhibition of glycolysis caused derepression of respiration leading to lower cellular ROS. In conclusion, these findings indicate that imatinib-resistant leukemic cells have an unexpected mitochondrial dysfunction that could be exploited for selective therapeutic intervention.

  1. Reduced-intensity allogeneic hematopoietic stem cell transplantation combined with imatinib has comparable event-free survival and overall survival to long-term imatinib treatment in young patients with chronic myeloid leukemia.

    Science.gov (United States)

    Zhao, Yanmin; Wang, Jiasheng; Luo, Yi; Shi, Jimin; Zheng, Weiyan; Tan, Yamin; Cai, Zhen; Huang, He

    2017-08-01

    The relative merits of reduced intensity hematopoietic stem cell transplantation (RIST) for chronic myeloid leukemia (CML) in the first chronic phase (CP) in imatinib era have not been evaluated. The study was designed to compare the outcomes of combination therapy of RIST plus imatinib (RIST + IM) vs. imatinib (IM) alone for young patients with early CP (ECP) and late CP (LCP). Of the patients, 130 were non-randomly assigned to treatment with IM alone (n = 88) or RIST + IM (n = 42). The 10-year overall survival (OS) and event-free survival (EFS) were comparable between RIST + IM and IM groups. LCP, high Sokal score, and no complete cytogenetic response at 3 months were adverse prognostic factors for survival, but only the time from diagnosis to IM was an independent predictor after multivariate analysis. For ECP, IM was similar to RIST + IM, with 10-year EFS rates of 77.2 vs. 81.6% (p = 0.876) and OS rates of 93.8 vs. 87.9% (p = 0.102), respectively. For LCP, both treatments resulted in similar survival, but more patients in the imatinib group experienced events (10-year EFS 40.8 vs. 66.7%, p = 0.047). The patients with higher EBMT risk scores had an inferior survival than those with lower scores (69.2 vs. 92.9%, p = 0.04). We concluded that RIST + IM was comparable to IM in terms of OS and EFS. However, RIST + IM was more affordable than IM alone in a 10-year scale. Thus, RIST + IM could be considered as an alternative treatment option, especially when the patients have low EBMT risk scores and demand a definite cure for CML.

  2. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib.

    LENUS (Irish Health Repository)

    Kinsella, Paula

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC(50)). Response for each culture was compared with the EGFR\\/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile.

  3. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

    International Nuclear Information System (INIS)

    Kinsella, Paula; Howley, Rachel; Doolan, Padraig; Clarke, Colin; Madden, Stephen F.; Clynes, Martin; Farrell, Michael; Amberger-Murphy, Verena

    2012-01-01

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC 50 ). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: ► Non-responders had low EGFR expression, high PDGFR-β, and a low proliferation rate. ► PTEN is not indicative of response to a TKI. ► Erlotinib response was not associated with expression of the proteins examined. ► Imatinib-response correlated with expression of PDGFR-α. ► Gefitinib response correlated with increased expression of EGFR.

  4. Preoperative radium therapy and radical hysterectomy in the treatment of cervical cancer stage IB, IIA, and initial IIB

    International Nuclear Information System (INIS)

    Salum, Resalla; Lopes, Edison R.; Souza, Maria A.H. de

    1995-01-01

    Patients with IB, IIa and in initial IIb cervical cancer were randomized for combined therapy, consisting of one or two radium insertion followed by Wertheim Meigs operation performed 40 days later. We look for the early and late complications of the treatment, residual cancer after radiotherapy and survival without recurrence. The project begin in 1965 and ended in 1986. All the operations were done by one of the investigators and 116 patients were analysed. The age ranged from 21 to 75 years with an average of 4.18 years. During the operations 31 (26.72%) patients needed 1.500 cc or greater amount of blood transfusion and we have 3 iliac veins lesions. Managing the ureters, we do our best to leave the posterior fascia as intact as possible. Post operative complications ranged from minor (fever, localised pelvic infections, temporary popliteal nerve paralysis) to evisceration (3 patients) deep venous thrombosis (3 patients) and two early urinary fistulas. Late complications were seen in patients submitted to sequential teletherapy irradiation. One uretrovaginal fistula occurred 10 month after treatment, another one, 7 years later and the third one 24 years later. One patient develop hydronefrosis and enterocolite after 7.000 rads of teletherapy and another one rectovaginal fistula 13 years after initial therapy. The shortening of the vagina making impossible the intercourse was seen in 7 patients. By the histological examination, the cervix was sterilized in 73.3 % of the patients. Residual cancer was found according the original size of the tumour and the stage of the disease. Studying different combinations between the existence of residual cervical cancer with positive or negative limphnodes and making a correlation with survival, we found the critical points is to have positive cervix and [positive lymphonodes. The five years survival (life table methodology) for stage 1 lesion was 96%; stage II, 67%. At ten years survival was slighted different. With positive

  5. Initial Results of Retrospective Study: Preoperative Transurethral Excision Plus Chemotherapy and Radiation Therapy and Trial of Bladder Preservation

    International Nuclear Information System (INIS)

    Gammal El-Deen, H.S.

    2007-01-01

    For patients with invasive bladder cancer the usual recommended treatment is radical cystectomy, although transurethral resection of the tumor, systemic chemotherapy, and radiotherapy are each effective in some patients. This retrospective study evaluated the experience of the Clinical Oncology Department, Tanta University Hospital with combined modality treatment and selective bladder preservation in patients with muscle-invading bladder cancer with assessment of its safety, tolerance, and efficacy to determine whether these treatments in combination might be as effective as radical cystectomy and thus might allow the bladder to be preserved and the cancer cured and to identify factors that may predict treatment response, risk of relapse and survival. Patients and Methods: Between January 2000 and January 2006, 55 consecutive patients with muscle invading bladder cancer (stages T2 through T4, NX M0) were treated with as complete transurethral surgery as possible, followed by induction combination chemotherapy, and irradiation with 4500 cGy with concurrent cisplatin administration. Urologic evaluation by cystoscopy, cytology, and re biopsy 2-3 weeks later of the tumor response directed further therapy: either radical cystectomy in the patients who had incomplete responses, or additional chemotherapy with the same drugs and doses and radiotherapy up to 6480 cGy in the patients who had complete responses. The median follow-up was 48 months. Results: In 37 patients (67.3%) the bladder was free of invasive tumor and functioning well, even though in 13(23.6%) a superficial tumor recurred and required further transurethral surgery and intravesical drug therapy. Of the 18 (32.7%) patients who still had detectable tumor after initial treatment, all of them underwent radical cystectomy. None of the patients had required a cystectomy for radiation toxicity. Of the 37 (67.3%) patients who had complete responses with no tumor detectable on urine cytology or re biopsy after

  6. Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

    Science.gov (United States)

    Mazza, Elena; Brandes, Alba; Zanon, Silvia; Eoli, Marika; Lombardi, Giuseppe; Faedi, Marina; Franceschi, Enrico; Reni, Michele

    2016-01-01

    Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75%, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75%, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

  7. Low educational level but not low income impairs the achievement of cytogenetic remission in chronic myeloid leukemia patients treated with imatinib in Brazil

    Directory of Open Access Journals (Sweden)

    Monica Napoleão Fortes Rego

    2015-05-01

    Full Text Available OBJECTIVES: In Brazil, imatinib mesylate is supplied as the first-line therapy for chronic myeloid leukemia in the chronic phase through the public universal healthcare program, Sistema Único de Saúde (SUS. We studied the socio-demographic factors that influenced therapy success in a population in the northeast region of Brazil. METHODS: Patients with chronic myeloid leukemia from the state of Piauí were treated in only one reference center. Diagnosis was based on WHO 2008 criteria. Risk was assessed by Sokal, Hasford and EUTOS scores. Patients received 400 mg imatinib daily. We studied the influence of the following factors on the achievement of complete cytogenetic response within one year of treatment: age, clinical risk category, time interval between diagnosis and the start of imatinib treatment, geographic distance from the patient's home to the hospital, years of formal education and monthly income. RESULTS: Among 103 patients studied, the median age was 42 years; 65% of the patients had 2-9 years of formal education, and the median monthly income was approximately 100 US$. Imatinib was started in the first year after diagnosis (early chronic phase in 69 patients. After 12 months of treatment, 68 patients had a complete cytogenetic response. The Hasford score, delay to start imatinib and years of formal education influenced the attainment of a complete cytogenetic response, whereas income and the distance from the home to the healthcare facility did not. CONCLUSION: Patients require additional healthcare information to better understand the importance of long-term oral anticancer treatment and to improve their compliance with the treatment.

  8. Evaluation of the Safety of Imatinib Mesylate in 200 Iraqi Patients with Chronic Myeloid Leukemia in the Chronic Phase: Single-Center Study

    Directory of Open Access Journals (Sweden)

    Bassam Francis Matti

    2013-12-01

    Full Text Available OBJECTIVE: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML. During therapy, a few patients may develop hematological and non-hematological adverse effects. METHODS: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. RESULTS: Two hundred CML patients in chronic phase were included in this study; the male: female ratio was 0.7: 1 with mean age 39.06±13.21 years (ranged from 15-81 years. The study showed that the commonest hematological side effects were grade 2 anemia (12.5% followed by leukopenia (8% and thrombocytopenia (4%, while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%, followed by musculoskeletal pain (35.5%, then gastro-intestinal symptoms (vomiting, diarrhea (19%. Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. CONCLUSION: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively.

  9. Comparison of imatinib, dasatinib, nilotinib and INNO-406 in imatinib-resistant cell lines.

    Science.gov (United States)

    Deguchi, Yasuyuki; Kimura, Shinya; Ashihara, Eishi; Niwa, Tomoko; Hodohara, Keiko; Fujiyama, Yoshihide; Maekawa, Taira

    2008-06-01

    We compared the growth-inhibitory effects and inhibition profile of the SRC family kinases (SFKs) of imatinib, dasatinib, nilotinib and INNO-406. Dasatinib exhibited the strongest potency against BCR-ABL with little selectivity over SFKs. Nilotinib exhibited a weaker affinity than the other inhibitors, but was highly specific for ABL and may be useful for the treatment of P-glycoprotein overexpressing leukemic cells. INNO-406 had an intermediate affinity for BCR-ABL between that of dasatinib and nilotinib, and inhibited only SFKs LCK and LYN among SFKs. Both nilotinib and INNO-406 were potent inhibitors of the dasatinib-resistant T315A, F317L and F317V BCR-ABL mutations.

  10. B-Cell Chronic Lymphocytic Leukemia with 11q22.3 Rearrangement in Patient with Chronic Myeloid Leukemia Treated with Imatinib

    Directory of Open Access Journals (Sweden)

    Krzysztof Lewandowski

    2016-01-01

    Full Text Available The coexistence of two diseases chronic myeloid leukemia (CML and B-cell chronic lymphocytic leukemia (B-CLL is a rare phenomenon. Both neoplastic disorders have several common epidemiological denominators (they occur more often in men over 50 years of age but different origin and long term prognosis. In this paper we described the clinical and pathological findings in patient with CML in major molecular response who developed B-CLL with 11q22.3 rearrangement and Coombs positive hemolytic anemia during the imatinib treatment. Due to the presence of the symptoms of autoimmune hemolytic anemia and optimal CML response to the imatinib treatment, the decision about combined therapy with prednisone and imatinib was made. During the follow-up, the normalization of complete blood count and resolution of peripheral lymphadenopathy were noted. The hematologic response of B-CLL was diagnosed. The repeated FISH analysis of cultured peripheral blood lymphocytes showed 2% of cells carrying 11q22.3 rearrangement. At the same time, molecular monitoring confirmed the deep molecular response of CML. The effectiveness of such combination in the described case raises the question about the best therapeutic option in such situation, especially in patients with good imatinib tolerance and optimal response.

  11. Preoperative staging of rectal cancer.

    Science.gov (United States)

    Smith, Neil; Brown, Gina

    2008-01-01

    Detailed preoperative staging using high resolution magnetic resonance imaging (MRI) enables the selection of patients that require preoperative therapy for tumour regression. This information can be used to instigate neoadjuvant therapy in those patients with poor prognostic features prior to disturbing the tumour bed and potentially disseminating disease. The design of trials incorporating MR assessment of prognostic factors prior to therapy has been found to be of value in assessing treatment modalities and outcomes that are targeted to these preoperative prognostic subgroups and in providing a quantifiable assessment of the efficacy of particular chemoradiation treatment protocols by comparing pre-treatment MR staging with post therapy histology assessment. At present, we are focused on achieving clear surgical margins of excision (CRM) to avoid local recurrence. We recommend that all patients with rectal cancer should undergo pre-operative MRI staging. Of these, about half will have good prognosis features (T1-T3b, N0, EMVI negative, CRM clear) and may safely undergo primary total mesorectal excision. Of the remainder, those with threatened or involved margins will certainly benefit from pre-operative chemoradiotherapy with the aim of downstaging to permit safe surgical excision. In the future, our ability to recognise features predicting distant failure, such as extramural vascular invasion (EMVI) may be used to stratify patients for neo-adjuvant systemic chemotherapy in an effort to prevent distant relapse. The optimal pre-operative treatment regimes for these patients (radiotherapy alone, systemic chemotherapy alone or combination chemo-radiotherapy) is the subject of current and future trials.

  12. Imatinib mesylate in chronic myelogenous leukemia: a Congolese ...

    African Journals Online (AJOL)

    Major cytogenetic response was noticed in 87.18%. After a median follow up of 12 months, chronic myeloid leukemia had not progressed to the accelerated or blastic phase in an estimated 91.8% of patients and 86.6% were alive. Conclusion: Imatinib is effective in newly chronic phase chronic myeloid leukemia patient ...

  13. Women Administered Standard Dose Imatinib for Chronic Myeloid Leukemia Have Higher Dose-Adjusted Plasma Imatinib and Norimatinib Concentrations Than Men.

    Science.gov (United States)

    Belsey, Sarah L; Ireland, Robin; Lang, Kathryn; Kizilors, Aytug; Ho, Aloysius; Mufti, Ghulam J; Bisquera, Alessandra; De Lavallade, Hugues; Flanagan, Robert J

    2017-10-01

    The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg·d. A predose plasma imatinib concentration of >1 mg·L is associated with improved clinical response. This study aimed to assess the plasma imatinib and norimatinib concentrations attained in patients with chronic myeloid leukemia administered standard doses of imatinib adjusted for dose, age, sex, body weight, and response. We evaluated data from a cohort of patients treated between 2008 and 2014 with respect to dose, age, sex, body weight, and response. The study comprised 438 samples from 93 patients (54 male, 39 female). The median imatinib dose was 400 mg·d in men and in women. The plasma imatinib concentration ranged 0.1-5.0 mg·L and was below 1 mg·L in 20% and 16% of samples from men and women, respectively. The mean dose normalized plasma imatinib and norimatinib concentrations were significantly higher in women in comparison with men. This was partially related to body weight. Mixed effects ordinal logistic regression showed no evidence of an association between sex and plasma imatinib (P = 0.13). However, there was evidence of an association between sex and plasma norimatinib, with higher norimatinib concentrations more likely in women than in men (P = 0.02). Imatinib therapeutic drug monitoring only provides information on dosage adequacy and on short-term adherence; longer-term adherence cannot be assessed. However, this analysis revealed that approximately 1 in 5 samples had a plasma imatinib concentration <1 mg·L, which was suggestive of inadequate dosage and/or poor adherence and posed a risk of treatment failure. Higher imatinib exposure in women may be a factor in the increased rate of long-term, stable, deep molecular response (undetectable breakpoint cluster-Abelson (BCR-ABL) transcript levels with a PCR sensitivity of 4.5 log, MR4.5) reported in women.

  14. Analysis of motion of the rectum during preoperative intensity modulated radiation therapy for rectal cancer using cone-beam computed tomography

    International Nuclear Information System (INIS)

    Yamashita, Hideomi; Takenaka, Ryousuke; Sakumi, Akira; Haga, Akihiro; Otomo, Kuni; Nakagawa, Keiichi

    2015-01-01

    The purpose of the present study was to quantify the inter-fractional motion of the rectum and the rectal and bladder volumes using CBCT scans taken during chemoradiation therapy (CRT) for rectal cancer. Also, assessment was made for a better margin for simultaneous integrated boost - intensity modulated radiation therapy (SIB-IMRT) for rectal cancer. There were 32 patients in this study undergoing preoperative CRT for rectal cancer. Each rectum and bladder was contoured on all planning CTs and CBCTs (day 1, 7, 13, 19, 25). The target volume was configured by adding margins (0, 3, 5, 7, 10, and 15 mm) to the rectum on planning CT. The respective percentage of rectal volume that exceeds the target volume was calculated for each of these margins. The percentage of bladder volume that exceeds the bladder volume in the planning CT and motion of the center of gravity of rectum were also analyzed. Planning CTs and series of each 5 CBCTs for 32 patients were analyzed in this study. The rectal volume tended to shrink week after week. The mean values (± SD) in the 32 series per patient of the percentage of rectum on the CBCTs exceeding target volume in which the margins of 0, 3, 5, 7, 10, and 15 mm were added to the rectum on planning CT were 20.7 ± 12.5%, 7.2 ± 8.3%, 3.9 ± 5.9%, 2.1 ± 3.9%, 0.7 ± 1.8%, and 0.1 ± 0.3%, respectively. No association was seen between the percentage of changes of bladder volume and motion of rectal centroid. In this study, we estimated the motion of the rectum using planning CT and CBCT. Ten to fifteen mm is a sufficient margin for the rectum during SIB-IMRT for rectal cancer in the supine position

  15. NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu [Massachusetts General Hospital, Boston, Massachusetts (United States); Moughan, Jennifer [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Garofalo, Michael C. [University of Maryland School of Medicine, Baltimore, Maryland (United States); Bendell, Johanna [Sarah Cannon Research Institute, Nashville, Tennessee (United States); Berger, Adam C. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Oldenburg, Nicklas B.E. [North Main Radiation Oncology, Providence, Rhode Island (United States); Anne, Pramila Rani [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Perera, Francisco [London Regional Cancer Program/Western Ontario, London, Ontario (Canada); Lee, R. Jeffrey [Intermountain Medical Center, Salt Lake City, Utah (United States); Jabbour, Salma K. [Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Nowlan, Adam [Piedmont Hospital, Atlanta, Georgia (United States); DeNittis, Albert [Main Line Community Clinical Oncology Program, Wynnewood, Pennsylvania (United States); Crane, Christopher [University of Texas-MD Anderson Cancer Center, Houston, Texas (United States)

    2015-09-01

    Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

  16. Quality of Life Outcomes From a Phase 2 Trial of Short-Course Radiation Therapy Followed by FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khwaja, Shariq S.; Roy, Amit; Markovina, Stephanie; Dewees, Todd A. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Hunt, Steven [Section of Colorectal Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Tan, Benjamin [Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Myerson, Robert J.; Olsen, Jeffrey R. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Parikh, Parag J., E-mail: pparikh@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2016-08-01

    Purpose: A prospective phase 2 trial of short-course (SC) radiation therapy (RT) with 25 Gy over 5 fractions, followed by 4 cycles of 5-fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) before surgery was recently completed at our institution. We present here the patient-reported quality of life (QOL) outcomes from this trial. Methods and Materials: Eighty patients with cT3/T4, any N, any M rectal adenocarcinoma planned for resection were enrolled between 2009 and 2012. The QOL data were obtained prospectively using the Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire before RT, before surgery, and 1 year after surgery. The previously validated minimally importance difference (MID) method was used to measure clinically significant QOL changes in FACT-C scores for each patient across time points. We examined the role of ostomy on QOL. We also compared QOL with disease outcomes and physician-reported toxicity. Results: The FACT-C questionnaire was completed by 97% of patients before RT, 85% immediately before surgery, and 62% 1 year after surgery. There was no statistically significant change in mean FACT-C scores from before treatment to after treatment. The majority of patients had either no change or an increase in QOL 1 year after treatment using the MID method. There were significant changes in QOL between patients with ostomy versus no ostomy 1 year after treatment for functional well-being (FWB) (14.81 vs 20.52, P=.018) and the colorectal cancer subscale (CCS) using the MID method (P=.004). Patients without ostomy reported stable changes in bowel control 1 year after surgery. There was no statistically significant correlation between QOL and disease recurrence, pathologic complete response, pathologic T stage downstaging, or acute/late toxicity. Conclusions: SC-RT and sequential mFOLFOX6 as preoperative therapy for rectal cancer results in stable patient-reported QOL outcomes 1 year after treatment. These findings in conjunction

  17. Quality of Life Outcomes From a Phase 2 Trial of Short-Course Radiation Therapy Followed by FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

    International Nuclear Information System (INIS)

    Khwaja, Shariq S.; Roy, Amit; Markovina, Stephanie; Dewees, Todd A.; Hunt, Steven; Tan, Benjamin; Myerson, Robert J.; Olsen, Jeffrey R.; Parikh, Parag J.

    2016-01-01

    Purpose: A prospective phase 2 trial of short-course (SC) radiation therapy (RT) with 25 Gy over 5 fractions, followed by 4 cycles of 5-fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) before surgery was recently completed at our institution. We present here the patient-reported quality of life (QOL) outcomes from this trial. Methods and Materials: Eighty patients with cT3/T4, any N, any M rectal adenocarcinoma planned for resection were enrolled between 2009 and 2012. The QOL data were obtained prospectively using the Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire before RT, before surgery, and 1 year after surgery. The previously validated minimally importance difference (MID) method was used to measure clinically significant QOL changes in FACT-C scores for each patient across time points. We examined the role of ostomy on QOL. We also compared QOL with disease outcomes and physician-reported toxicity. Results: The FACT-C questionnaire was completed by 97% of patients before RT, 85% immediately before surgery, and 62% 1 year after surgery. There was no statistically significant change in mean FACT-C scores from before treatment to after treatment. The majority of patients had either no change or an increase in QOL 1 year after treatment using the MID method. There were significant changes in QOL between patients with ostomy versus no ostomy 1 year after treatment for functional well-being (FWB) (14.81 vs 20.52, P=.018) and the colorectal cancer subscale (CCS) using the MID method (P=.004). Patients without ostomy reported stable changes in bowel control 1 year after surgery. There was no statistically significant correlation between QOL and disease recurrence, pathologic complete response, pathologic T stage downstaging, or acute/late toxicity. Conclusions: SC-RT and sequential mFOLFOX6 as preoperative therapy for rectal cancer results in stable patient-reported QOL outcomes 1 year after treatment. These findings in conjunction

  18. Impact of CYP2C8*3 polymorphism on in vitro metabolism of imatinib to N-desmethyl imatinib.

    Science.gov (United States)

    Khan, Muhammad Suleman; Barratt, Daniel T; Somogyi, Andrew A

    2016-01-01

    1. Imatinib is metabolized to N-desmethyl imatinib by CYPs 3A4 and 2C8. The effect of CYP2C8*3 genotype on N-desmethyl imatinib formation was unknown. 2. We examined imatinib N-demethylation in human liver microsomes (HLMs) genotyped for CYP2C8*3, in CYP2C8*3/*3 pooled HLMs and in recombinant CYP2C8 and CYP3A4 enzymes. Effects of CYP-selective inhibitors on N-demethylation were also determined. 3. A single-enzyme Michaelis-Menten model with autoinhibition best fitted CYP2C8*1/*1 HLM (n = 5) and recombinant CYP2C8 kinetic data (median ± SD Ki = 139 ± 61 µM and 149 µM, respectively). Recombinant CYP3A4 showed two-site enzyme kinetics with no autoinhibition. Three of four CYP2C8*1/*3 HLMs showed single-enzyme kinetics with no autoinhibition. Binding affinity was higher in CYP2C8*1/*3 than CYP2C8*1/*1 HLM (median ± SD Km = 6 ± 2 versus 11 ± 2 µM, P=0.04). CYP2C8*3/*3 (pooled HLM) also showed high binding affinity (Km = 4 µM) and single-enzyme weak autoinhibition (Ki = 449 µM) kinetics. CYP2C8 inhibitors reduced HLM N-demethylation by 47-75%, compared to 0-30% for CYP3A4 inhibitors. 4. In conclusion, CYP2C8*3 is a gain-of-function polymorphism for imatinib N-demethylation, which appears to be mainly mediated by CYP2C8 and not CYP3A4 in vitro in HLM.

  19. Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl

    Science.gov (United States)

    2010-01-01

    Background Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB) transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I. Results In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I) and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5) or imatinib-resistant (KBM5-T315I) CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways. Conclusion To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for further drug development to

  20. Analysis of Survival of Patients with Chronic Myeloid Leukemia Treated with Imatinib in the Last 15 Years in Lebanon.

    Science.gov (United States)

    Massoud, Marcel; Sakr, Riwa; Kerbage, Fouad; Makdissi, Joseph; Hawi, Jenny; Rached, Layale; Nasr, Fady; Chahine, Georges

    2017-07-01

    In the 2000s, the introduction of the tyrosine kinase inhibitor (TKI), imatinib, improved the survival outcomes of patients with chronic myeloid leukemia (CML). In Lebanon, we rapidly adopted this treatment strategy. To the best of our knowledge, this is the first study reporting the survival rates of Lebanese CML patients. We examined the rates of major molecular response (MMR) and complete cytogenetic response (CCyR) and analyzed the overall survival, progression-free survival, and event-free survival of CML patients treated with front-line imatinib in 3 university hospitals in Lebanon. We retrospectively reviewed the medical records of 46 patients diagnosed with CML and treated with front-line imatinib 400 mg/day from 2000 and followed up to 2015. In all patients, initially, 2 diagnostic tests were performed: cytogenetic analysis and qualitative molecular testing of the BCR-ABL transcript. The male-to-female sex ratio was 3:1. The median age at diagnosis was 49 years, and the mean age was 44.52 years. At diagnosis, 46 patients were in the chronic phase. All patients started imatinib 400 mg/day. Of the 46 patients, 35 had a typical karyotype, 8 an atypical karyotype, and 3 hypoploidism. The MMR rate at 18 months was 58.69%. The cumulative CCyR rate at 18 months of therapy with imatinib at the standard dose was 67.39%. The event-free survival rate was 75.86% and 74.14% at 5 and 8 years, respectively. The progression-free survival rate was 77.59% and 75.86% at 5 and 8 years, respectively. The overall survival rate was 98.27% and 98.27% at 5 and 8 years, respectively. Of the 46 patients, 12 developed disease progression and were salvaged by second-generation TKIs. These 12 patients were still alive with a MMR. In our study population, the achievement of a MMR and CCyR and overall survival, progression-free survival, and event-free survival were similar to previous published data. Reaching high survival rates with a first-generation TKI in a country with limited

  1. Long-Term Follow-Up of Preoperative Pelvic Radiation Therapy and Concomitant Boost Irradiation in Locally Advanced Rectal Cancer Patients: A Multi-Institutional Phase II Study (KROG 04-01)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Hoon [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of); Department of Radiation Oncology, St. Vincent' s Hospital, Catholic University of Korea, Suwon (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Go-Yang (Korea, Republic of); Nam, Taek-Keun [Department of Radiation Oncology, Chonnam National University Hospital, Hwa-Sun (Korea, Republic of); Yoon, Sei-Chul [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of); Lee, Doo Seok [Department of Colorectal Surgery, Daehang Hospital, Seoul (Korea, Republic of); Park, Ji Won; Oh, Jae Hwan; Chang, Hee Jin [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Go-Yang (Korea, Republic of); Yoon, Mee Sun; Jeong, Jae-Uk [Department of Radiation Oncology, Chonnam National University Hospital, Hwa-Sun (Korea, Republic of); Jang, Hong Seok, E-mail: hsjang11@catholic.ac.kr [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of)

    2012-11-15

    Purpose: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. Methods and Materials: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. Results: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P = .045) and N (P = .032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P = .025) and overall survival (P = .031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. Conclusion: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and

  2. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, In Ja [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Kim, Hee Cheol [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Nam Kyu [Section of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong-Rok [Department of Surgery, Chonnam National University Hwansun Hospital, Gwangju (Korea, Republic of); Kang, Sung-Bum [Department of Surgery, Seoul National University Bungdang Hospital, Bundang (Korea, Republic of); Choi, Gyu-Seog [Division of Colorectal Cancer Center, Kyungpook National University Medical Center, Daegu (Korea, Republic of); Lee, Kang Young [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seon-Hahn [Department of Surgery, Korea University Anam Hospital, Seoul (Korea, Republic of); Oh, Seung Taek [Department of Surgery, Seoul St. Mary Hospital, Catholic University, Seoul (Korea, Republic of); Lim, Seok-Byung; Kim, Jin Cheon [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Oh, Jae Hwan; Kim, Sun Young [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Lee, Woo Yong [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jung Bok [Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Yu, Chang Sik, E-mail: csyu@amc.seoul.kr [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of)

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  3. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

    Science.gov (United States)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    International Nuclear Information System (INIS)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-01-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits

  5. Validation of the CPS+EG and Neo-Bioscore staging systems after preoperative systemic therapy for breast cancer in a single center in China.

    Science.gov (United States)

    Xu, Ling; Duan, Xuening; Zhou, Bin; Liu, Yinhua; Ye, Jingming; Liu, Zhaorui; Ma, Chao; Zhang, Hong; Zhang, Shuang; Zhang, Lanbo; Zhao, Jianxin; Cheng, Yuanjia

    2018-04-17

    Prognostic assessment after preoperative systemic therapy (PST) plays a vital role in determining treatment in breast cancer patients. Many researchers have sought to develop a system to quantitate residual tumor and its correlation with prognosis after PST. This retrospective study validated the CPS + EG staging system and Neo-Bioscore in a single center in China. Data from patients with non-metastatic primary breast cancer who were treated with PST and surgery from Jan. 2008 to Dec. 2014 at the Breast Disease Center of Peking University First Hospital, China, were reviewed. DFS, DSS and OS were calculated using the K-M curve and AUC. Multivariate analysis was used for a Cox proportional hazards model. All calculations were performed with SAS 9.4. A total of 403 patients were enrolled in this study. The median follow-up period was 45 (range 11-107) months. The five-year DFS, DSS and OS rates were 86.4%, 91.2% and 90.5%, respectively. The CS, PS, CPS + EG staging system and Neo-Bioscore stratified patients according to DFS, DSS, and OS after PST, with all P values < 0.0001. The CPS + EG staging system and Neo-Bioscore stratified prognosis after PST better than CS. HER2-positive patients without trastuzumab treatment had obviously worse DFS and OS than other subgroups with different HER2 statuses that scored a 3 in the Neo-Bioscore system. The CPS + EG staging system and Neo-Bioscore can improve prognostic prediction in non-pCR breast cancer patients after PST and, provided unfavorable prognostic factors such as insufficient treatment are incorporated, will have broader clinical applicability. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Response of Complex Undefined Hypereosinophilic Syndrome to Treatment with Imatinib.

    Science.gov (United States)

    Yılmaz, İnsu; Kaynar, Leylagül; Tutar, Nuri; Pala, Çiğdem; Canöz, Özlem; Yıldırım, Afra; Büyükoğlan, Hakan; Gülmez, İnci

    2016-07-01

    Hypereosinophilic syndomes (HESs) include potentially lethal multisystem disorders characterized by eosinophilic infiltration of a variable spectrum of target organs, predominantly the skin, heart, lungs, gastrointestinal tract, and nervous system. Based on recent advances in molecular and genetic diagnostic techniques and increasing experience with differences in clinical features and prognosis, subtypes have been defined, including "myeloproliferative-HES ", "lymphocytic-HES", "familial eosinophilia", "overlap HES", "undefined HES" ("complex undefined HES", "simple undefined HES", "episodic undefined HES") and "eosinophil associated diseases" (such as Churg-Strauss syndrome). HES should be kept in mind in the differential diagnosis of eosinophilic lung diseases especially in patients with peripheral eosinophilia and pulmonary infiltrates. Corticosteroids represent an effective firstline approach to decreasing eosinophil counts in the majority of cases. Imatinib might be used for corticosteroid nonresponders. We herein report a patient with "complex undefined HES" who had disease resistant to corticosteroids, but who had a significant response after treatment with imatinib.

  7. A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition.

    Science.gov (United States)

    Schiffmann, L M; Brunold, M; Liwschitz, M; Goede, V; Loges, S; Wroblewski, M; Quaas, A; Alakus, H; Stippel, D; Bruns, C J; Hallek, M; Kashkar, H; Hacker, U T; Coutelle, O

    2017-02-28

    Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy. Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg -1 body weight) or high (5 mg kg -1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared. ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy. Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

  8. Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

    Science.gov (United States)

    Cariani, E; Capucci, M; Micheletti, M; Spalenza, F; Zanella, I; Albertini, A; Rossi, G

    2003-06-01

    Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

  9. 31P MR spectroscopic imaging in preoperative embolization therapy of meningiomas; Phosphor-31-MR-spektroskopische Bildgebung bei praeoperativer Embolisationstherapie von Meningeomen

    Energy Technology Data Exchange (ETDEWEB)

    Blankenhorn, M. [Psychiatrische Universitaetsklinik, Ulm (Germany). Abteilung III; Bachert, P.; Kaick, G. van [Deutsches Krebsforschungszentrum Heidelberg (Germany). Forschungsschwerpunkt Radiologische Diagnostik; Semmler, W. [Freie Univ. Berlin (Germany). Inst. fuer Diagnostikforschung; Ende, G. [Zentralinstitut fuer Seelische Gesundheit, Mannheim (Germany). NMR-Forschung in der Psychiatrie; Tronnier, V. [Neurochirurgische Klinik, Klinikum der Universitaet, Heidelberg (Germany); Sartor, K. [Neurologische Klinik, Klinikum der Universitaet, Heidelberg (Germany). Abt. Neuroradiologie

    1999-06-01

    Purpose: {sup 31}P MR spectroscopic imaging ({sup 31}P SI) was evaluated in a clinical study as a method for monitoring presurgical devascularization of meningiomas. The aim was to assess noninvasively metabolic alterations in tumor and in healthy brain tissue before and after embolization. Methods: Localized {sup 31}P MR spectra of the brain were obtained by means of 2D-SI (voxel size: 36 cm{sup 3}) using a 1,5-T whole-body MR tomograph. Results: Eleven of 19 patients with intracranial meningiomas examined in this study underwent preoperative embolization therapy; eight patients were examined before and after treatment. After embolization, alterations of pH and of the concentrations of high-energy phosphates (nucleoside-5`triphosphate=NTP, phosphocreatine=PCr), inorganic phosphate (P{sub i}), and membrane constituents were observed in the tumors. A tendency of [P{sub i}] increase and decrease of [NTP], [PCr], and pH predominated, which is explained by ischemic processes after tumor devascularization. Conclusion: {sup 31}P SI is applicable in clinical studies and detects alterations of phosphate metabolism in a meningioma after embolization. (orig.) [Deutsch] Ziel: Die {sup 31}P-MR-spektroskopische Bildgebung ({sup 31}P-SI) wurde im Rahmen der praeoperativen Embolisationstherapie von Patienten mit Meningeomen als Methode zur Therapieverlaufskontrolle klinisch geprueft. Ziel der Studie war die nichtinvasive Erfassung von Veraenderungen im Metabolismus der Tumoren vor und nach Embolisation im Vergleich zum gesunden Hirngewebe. Methoden: Lokalisierte {sup 31}P-MR-Spektren des Gehirns wurden mit 2D-SI (Voxelgroesse: 36 cm{sup 3}) an einem 1,5-T-Ganzkoerper-MR-Tomographen aufgenommen. Ergebnisse: Elf von insgesamt 19 untersuchten Patienten unterzogen sich einer praeoperativen Embolisation, bei acht Patienten konnte eine Verlaufskontrolle durchgefuehrt werden. Nach Embolisation wurden Veraenderungen des pH und der Konzentrationen von energiereichen Phosphaten (Nukleosid

  10. Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome.

    Science.gov (United States)

    King, Aileen J F; Griffiths, Lisa A; Persaud, Shanta J; Jones, Peter M; Howell, Simon L; Welsh, Nils

    2016-05-01

    Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome. Methods Islets were isolated from C57Bl/6 mice and pre-cultured with imatinib prior to exposure to streptozotocin and cytokines in vitro. Cell viability and glucose-induced insulin secretion were measured. For transplantation experiments, islets were pre-cultured with imatinib for either 72 h or 24 h prior to transplantation into streptozotocin-diabetic C57Bl/6 mice. In one experimental series mice were also administered imatinib after islet transplantation. Results Imatinib partially protected islets from beta cell death in vitro. However, pre-culturing islets in imatinib or administering the drug to the mice in the days following islet transplantation did not improve blood glucose concentrations more than control-cultured islets. Conclusion Although imatinib protected against beta cell death from cytokines and streptozotocin in vitro, it did not significantly improve syngeneic islet transplantation outcome.

  11. Long-term safety and efficacy of dasatinib in the treatment of chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib

    Directory of Open Access Journals (Sweden)

    Shoumariyeh K

    2014-09-01

    Full Text Available Khalid Shoumariyeh, Nikolas von BubnoffDepartment of Hematology, Oncology and Stem Cell Transplantation, University Hospital Freiburg, Freiburg, Germany Abstract: Treatment of chronic myeloid leukemia (CML has undergone dramatic changes in the last decade. Dissecting the molecular pathways that lead to the development of this disease resulted in the development of targeted therapy against the molecular driver of CML, namely the aberrantly activated tyrosine kinase BCR-ABL1. By introducing the tyrosine kinase inhibitor imatinib to the treatment repertoire, the natural course of the disease has been dramatically altered and overall survival of patients with CML prolonged substantially. Nevertheless, a significant number of patients are primarily resistant, acquire resistance during the course of their disease, or do not tolerate the intake of imatinib due to adverse effects. Second-generation tyrosine kinase inhibitors were developed in an attempt to overcome these problems. Dasatinib is a potent oral kinase inhibitor that was originally developed as an Src-kinase inhibitor but exhibited promising potency against BCR-ABL1 as well. Phase I and II trials demonstrated efficacy in patients failing imatinib, and thus dasatanib was approved in 2006 for the treatment of imatinib-resistant or -intolerant patients with chronic-phase CML harboring the BCR-ABL1 fusion protein. It has since shown promising efficacy and good overall tolerability in subsequent clinical trials, including the Phase III first-line DASISION trial that led to the extension of its approval for first-line treatment of chronic-phase CML. The following review summarizes the available data on the long-term efficacy and safety of dasatinib as a second-line therapy in chronic-phase CML. Keywords: BCR-ABL1, TKI, CML-CP, second-line treatment

  12. Time-series analysis in imatinib-resistant chronic myeloid leukemia K562-cells under different drug treatments.

    Science.gov (United States)

    Zhao, Yan-Hong; Zhang, Xue-Fang; Zhao, Yan-Qiu; Bai, Fan; Qin, Fan; Sun, Jing; Dong, Ying

    2017-08-01

    Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein. Imatinib is the first-line treatment of CML; however, many patients are resistant to this drug. In this study, we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments. GSE24946 was downloaded from the GEO database, which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5). Three drug treatment groups were considered for this study: arsenic trioxide (ATO), AMN107, and ATO+AMN107. Each group had one sample at each time point (3, 12, 24, and 48 h). Time-series genes with a ratio of standard deviation/average (coefficient of variation) >0.15 were screened, and their expression patterns were revealed based on Short Time-series Expression Miner (STEM). Then, the functional enrichment analysis of time-series genes in each group was performed using DAVID, and the genes enriched in the top ten functional categories were extracted to detect their expression patterns. Different time-series genes were identified in the three groups, and most of them were enriched in the ribosome and oxidative phosphorylation pathways. Time-series genes in the three treatment groups had different expression patterns and functions. Time-series genes in the ATO group (e.g. CCNA2 and DAB2) were significantly associated with cell adhesion, those in the AMN107 group were related to cellular carbohydrate metabolic process, while those in the ATO+AMN107 group (e.g. AP2M1) were significantly related to cell proliferation and antigen processing. In imatinib-resistant CML cells, ATO could influence genes related to cell adhesion, AMN107 might affect genes involved in cellular carbohydrate metabolism, and the combination therapy might regulate genes involved in cell proliferation.

  13. Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with imatinib mesylate against chronic myelogenous leukemia cell lines

    Directory of Open Access Journals (Sweden)

    Xin P

    2017-04-01

    Full Text Available Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu Department of Haematology, First Hospital of Quanzhou Affiliated to Fujian Medical University, Licheng, Quanzhou, Fujian Province, China Background: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML cells and sensitivity of tyrosine kinase inhibitor in vitro.Methods: Two human CML cell lines, K562 and KBM7R (T315I mutant strain, were used. The proliferation of CML cells was detected by MTS (Owen’s reagent assay. Cell cycle and apoptosis assay were examined by flow cytometric analysis. The phosphorylation levels and the expression levels were both evaluated by Western blot analysis. NVP-BEZ235 in combination with imatinib was also used to reveal the effect on proliferation and apoptosis.Results: NVP-BEZ235 significantly inhibited the proliferation in a time- and dose-dependent manner, and the half-maximal inhibitory concentration values of NVP-BEZ235 inhibiting the proliferation of K562 and KBM7R were 0.37±0.21 and 0.43±0.27 µmol/L, respectively, after 48 h. Cell apoptosis assay showed that NVP-BEZ235 significantly increased the late apoptotic cells. Cell cycle analysis indicated that the cells were mostly arrested in G1/G0 phase after treatment by NVP-BEZ235. In addition, results also found that, after treatment by NVP-BEZ235, phosphorylation levels of Akt kinase and S6K kinase significantly reduced, and the expression levels of cleaved caspase-3 significantly increased; meanwhile, the expression levels of caspase-3, B-cell lymphoma-2, cyclin D1, and cyclin D2 significantly decreased, and the ratio of LC3II/LC3I was significantly increased with increased LC3II expression level. Moreover, imatinib in combination with NVP-BEZ235

  14. Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor

    International Nuclear Information System (INIS)

    Hwang, Jun-Eul; Yoon, Ju-Young; Bae, Woo-Kyun; Shim, Hyun-Jeong; Cho, Sang-Hee; Chung, Ik-Joo

    2010-01-01

    Imatinib mesylate has been used for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST). The current recommended dose of imatinib is 400 mg/day that is increased to 800 mg/day in cases with disease progression. However, imatinib can be associated with diverse adverse events, which has limited its use. We report a case of severe adverse skin reactions with neutropenic fever during imatinib treatment in a patient with GIST. A 71-year-old man was admitted with a one month history of epigastric pain and a palpable mass in the right upper quadrant. An abdominal CT scan revealed a 20 × 19 cm intraabdominal mass with tumor invasion into the peritoneum. Needle biopsy was performed and the results showed spindle shaped tumor cells that were positive for c-KIT. The patient was diagnosed with unresectable GIST. Imatinib 400 mg/day was started. The patient tolerated the first eight weeks of treatment. However, about three months later, the patient developed a grade 4 febrile neutropenia and a grade 3 exfoliative skin rash. The patient recovered from this serious adverse events after discontinuation of imatinib with supportive care. However, the skin lesions recurred whenever the patient received imatinib over 100 mg/day. Therefore, imatinib 100 mg/day was maintained. Despite the low dose imatinib, follow up CT showed a marked partial response without grade 3 or 4 toxicities. The recommended dose of imatinib for the treatment of GIST is 400 mg/day but patients at risk for adverse drug reaction may benefit from lower doses. Individualized treatment is needed for such patients, and we may also try sunitinib as a alternative drug

  15. Chronic myeloid leukemia patients sensitive and resistant to imatinib treatment show different metabolic responses.

    Directory of Open Access Journals (Sweden)

    Jiye A

    Full Text Available The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML. However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML and patients resistant to imatinib (RCML had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA. In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention.

  16. An economic analysis of high-dose imatinib, dasatinib, and nilotinib for imatinib-resistant chronic phase chronic myeloid leukemia in China: A CHEERS-compliant article.

    Science.gov (United States)

    Wu, Bin; Liu, Maobai; Li, Te; Lin, Houwen; Zhong, Hua

    2017-07-01

    The aim of the study was to test the cost-effectiveness of dasatinib compared to high-dose imatinib and nilotinib in Chinese patients who were diagnosed with imatinib-resistant chronic myeloid leukemia in the chronic phase (CML-CP). A Markov model combined with clinical effectiveness, utility, and cost data was used. The sensitivity analyses were conducted to determine the robustness of the model outcomes. The impact of patient assistance programs (PAPs) was assessed. Treatment with dasatinib is expected to produce 3.65, 0.59, and 0.15 more quality-adjusted life years (QALYs) in comparison with high-dose imatinib (600 and 800 mg) and nilotinib, respectively. When a PAP was available, dasatinib yielded an incremental cost of $16,417 per QALY compared to imatinib (600 mg) and was cost-saving compared to imatinib (800 mg) and nilotinib. When PAP is available in the Chinese setting, dasatinib is likely to be a cost-effective strategy for patients with CML-CP standard-dose imatinib resistance. The results should be carefully explained due to the assumptions and limitations used in the study.

  17. Gemfibrozil impairs imatinib absorption and inhibits the CYP2C8-mediated formation of its main metabolite.

    Science.gov (United States)

    Filppula, A M; Tornio, A; Niemi, M; Neuvonen, P J; Backman, J T

    2013-09-01

    Cytochrome P450 (CYP) 3A4 is considered the most important enzyme in imatinib biotransformation. In a randomized, crossover study, 10 healthy subjects were administered gemfibrozil 600 mg or placebo twice daily for 6 days, and imatinib 200 mg on day 3, to study the significance of CYP2C8 in imatinib pharmacokinetics. Unexpectedly, gemfibrozil reduced the peak plasma concentration (Cmax) of imatinib by 35% (P Gemfibrozil also reduced the Cmax and area under the plasma concentration-time curve (AUC0-∞) of N-desmethylimatinib by 56 and 48% (P gemfibrozil reduced the Cmax/plasma concentration at 24 h (C24 h) ratios of imatinib and N-desmethylimatinib by 44 and 17% (P gemfibrozil. Our findings indicate significant participation of CYP2C8 in the metabolism of imatinib in humans, and support involvement of an intestinal influx transporter in imatinib absorption.

  18. Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates; Adenocarcinoma gastrico avancado. Analise da toxicidade e da influencia da radioterapia pre-operatoria nos indices de sobrevivencia a longo prazo

    Energy Technology Data Exchange (ETDEWEB)

    Malzoni, Carlos Eduardo

    1996-12-31

    The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author) 112 refs., 34 tabs.

  19. Advanced gastric adenocarcinoma. Influence of preoperative radiation therapy on toxicity and long-term survival rates; Adenocarcinoma gastrico avancado. Analise da toxicidade e da influencia da radioterapia pre-operatoria nos indices de sobrevivencia a longo prazo

    Energy Technology Data Exchange (ETDEWEB)

    Malzoni, Carlos Eduardo

    1997-12-31

    The surgical treatment of gastric cancer has better long-term survival rates when performed in patients with early gastric cancer. Worse results are obtained in treatment of advanced gastric cancer. Most patients in west centers are treated in advanced stages. A great number of them go through a surgical treatment unable by itself to cure them. the frequent local recurrence caused by failure of the surgical treatment has been keeping poor survival rates in patients with advanced gastric cancer for decades. The desire of improving survival is the reason of the use of adjuvant therapies. This paper achieved the retrospective study of the influence of preoperative radiation therapy (2000 cGy) in long-term survival rates (120 months) of patients with advanced gastric cancer on stages IIIa, IIIb and IV. The possible injuries caused in the liver and kidney were observed also as well as first group was treated by surgical and radiation therapies and the second received surgical treatment only. There was no statistical difference between the two groups when sex, age, race, occurrence of other diseases, nutritional assessment, TNM stage, occurrence of obstruction or bleeding caused by tumor, surgical procedure and hepatic and renal function were considered. Survival rates and changes on hepatic and renal function were statistically compared. The results showed a statistic improvement on the long-term survival rates of stage IIIa patients treated by preoperative radiation therapy. No statistic difference was observed on hepatic or renal function between the groups. No adverse influence of radiation therapy method was detected by the used parameters. There was no statistical difference between the two groups when immediate surgical complications were considered. (author) 112 refs., 34 tabs.

  20. Broncho-pulmonary toxicity in stage III non small cell lung cancer patients treated with taxol containing chemotherapy and concurrent preoperative or definitive radiation therapy

    International Nuclear Information System (INIS)

    Sharma, M. Maddie; Gupta-Burt, Shalina; Recine, Diane C.; Faber, L. Penfield; Warren, William H.; LaFollette, Suzanne; Lincoln, Sarah T.; Bonomi, Philip D.

    1997-01-01

    Purpose/Objective: The objective of this trial was to test the feasibility of taxol containing combination chemotherapy and concurrent radiation as preoperative or definitive treatment for stage III non small cell lung cancer patients. Methods and Materials: Thirty-three patients were treated on this trial. The initial regimen was (Group 1 pts.): paraplatin (P) (AUC of 4) on day 2, etoposide (E) 50 mg po days 1-5 and 8-12, cisplatin (C) 50 mg/m2 on day 21 and taxol (T) 35 mg/m2 escalated to 45 mg/m2 on days 1 and 8, 24 hr. infusion. After treatment of 10 pts., the regimen was modified as follows (Group 2 pts.): P (AUC of 4) on day 1, E 40 mg/m2 IV daily and days 2-5, and T 80 mg/m2 escalated to 120 mg/m2 on day 1, 3 hr. infusion. After the next 16 pts., the regimen was modified again as follows (Group 3 pts.): P (AUC of 4) on day 1 and T 120 mg/m2 escalated to 140 mg/m2 on day 1, 3 hr. infusion. Seven patients were treated on the latest version of the regimen for a total of 33 pts. The radiation given was uniform throughout the 3 groups. A dose of 4000 cGy in 20 fxs was given in the surgical arm and 6000 cGy in 30 fxs in the non surgical arm. Treatments were given at 200 cGy/fx. once a day, on a 2 weeks on, 2 weeks off basis. The RTOG Acute Radiation Morbidity Scoring Criteria was used to grade pneumonitis. Post-operative complications were defined as occurring early (less than or equal to 30 days) or late (greater than 30 days) following surgery. Results: Sixteen of the 33 patients went to surgery. Grade 3 radiation pneumonitis developed in 4 of the 33 patients (12%). There were no episodes of Grade 4 pneumonitis. Grade 3 pneumonitis occured in: One patient in Group 1, (RT dose 5800 cGy), 2 pts in Group 2 (RT dose 4000 cGy and 6000 cGy, respectively), and 1 pt in Group 3 (RT dose 6000 cGy). Major post-operative complications occurred in 6 of the 16 patients (37.5%) who went to surgery. In Group 1, 1 pt. required oxygen supplementation secondary to a significant

  1. [Literature review and presentation of our own research results regarding the effects on bone of tyrosine kinase inhibitors imatinib and nilotinib used in the treatment of oncohematological diseases].

    Science.gov (United States)

    Kirschner, Gyöngyi; Balla, Bernadett; Kósa, János; Horváth, Péter; Kövesdi, Andrea; Lakatos, Gergely; Takács, István; Nagy, Zsolt; Tóbiás, Bálint; Árvai, Kristóf; Lakatos, Péter

    2016-09-01

    Tyrosine kinase inhibitors are widely used for treatment of certain oncohematological diseases. Several clinical studies have confirmed that specific BCR-ABL tyrosine kinase inhibitors alter the physiological process of bone tissue in a complex and unclearly identified manner. Since these treatments are being given to more and more patients, and the therapy takes decades or lasts even lifelong, it is justifiable to obtain more detailed knowledge of the molecular background of these mechanisms. In this article the authors summarize preliminary research results and human clinical observations on imatinib and nilotinib which are related to bone metabolism, and present the results of their own experiments in in vitro osteoblast cultures. Based on the presented results, the effects of imatinib and nilotinib on bone cells depend on the concentration of imatinib and nilotinib, the maturation stage of the cells and the distribution ratio of receptor tyrosine kinase signaling pathways. In this study the authors firstly prepared a stop-gap, comprehensive review in the Hungarian literature, regarding the effects of tyrosine kinase inhibitors on bone metabolism. In addition they firstly performed whole transcriptome analysis on osteoblasts in order to obtain a better understanding of the cellular molecular mechanisms. Orv. Hetil., 2016, 157(36), 1429-1437.

  2. Frequency of ABL gene mutations in chronic myeloid leukemia patients resistant to imatinib and results of treatment switch to second-generation tyrosine kinase inhibitors.

    Science.gov (United States)

    Marcé, Silvia; Zamora, Lurdes; Cabezón, Marta; Xicoy, Blanca; Boqué, Concha; Fernández, Cristalina; Grau, Javier; Navarro, José-Tomás; Fernández de Sevilla, Alberto; Ribera, Josep-Maria; Feliu, Evarist; Millá, Fuensanta

    2013-08-04

    Tyrosine kinase inhibitors (TKI) have improved the management of patients with chronic myeloid leukemia (CML). However, a significant proportion of patients do not achieve the optimal response or are resistant to TKI. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Treatment with second-generation TKI has produced high rates of hematologic and cytogenetic responses in mutated ABL patients. The aim of this study was to determine the type and frequency of ABL mutations in patients who were resistant to imatinib or had lost the response, and to analyze the effect of second-generation TKI on their outcome. The presence of ABL mutations in 45 CML patients resistant to imatinib was evaluated by direct sequencing and was correlated with the results of the cytogenetic study (performed in 39 cases). The outcome of these patients after therapy with nilotinib or dasatinib was analyzed. ABL mutations were detected in 14 out of 45 resistant patients. Patients with clonal cytogenetic evolution tended to develop mutations more frequently than those without clonal evolution. Nine out of the 15 patients with ABL mutation responded to a treatment switch to nilotinib (n=4), dasatinib (n=2), interferon (n=1) or hematopoietic stem cell transplantation (n=2). The frequency of ABL mutations in CML patients resistant to imatinib is high and is more frequent among those with clonal cytogenetic evolution. The change to second-generation TKI can overcome imatinib resistance in most of the mutated patients. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  3. CYP2C8 Genotype Significantly Alters Imatinib Metabolism in Chronic Myeloid Leukaemia Patients.

    Science.gov (United States)

    Barratt, Daniel T; Cox, Hannah K; Menelaou, Andrew; Yeung, David T; White, Deborah L; Hughes, Timothy P; Somogyi, Andrew A

    2017-08-01

    The aims of this study were to determine the effects of the CYP2C8*3 and *4 polymorphisms on imatinib metabolism and plasma imatinib concentrations in chronic myeloid leukaemia (CML) patients. We genotyped 210 CML patients from the TIDELII trial receiving imatinib 400-800 mg/day for CYP2C8*3 (rs11572080, rs10509681) and *4 (rs1058930). Steady-state trough total plasma N-desmethyl imatinib (major metabolite):imatinib concentration ratios (metabolic ratios) and trough total plasma imatinib concentrations were compared between genotypes (one-way ANOVA with Tukey post hoc). CYP2C8*3 (n = 34) and *4 (n = 15) carriers had significantly higher (P  50% higher for CYP2C8*1/*4 than for CYP2C8*1/*1 and CYP2C8*3 carriers (2.18 ± 0.66 vs. 1.45 ± 0.74 [P < 0.05] and 1.36 ± 0.98 μg/mL [P < 0.05], respectively). CYP2C8 genotype significantly alters imatinib metabolism in patients through gain- and loss-of-function mechanisms.

  4. Prevention of heterotopic ossification about the hip: final results of two randomized trials in 410 patients using either preoperative or postoperative radiation therapy

    International Nuclear Information System (INIS)

    Seegenschmiedt, M. Heinrich; Keilholz, Ludwig; Martus, Peter; Goldmann, Axel; Woelfel, Rainer; Henning, Friedrich; Sauer, Rolf

    1997-01-01

    Purpose: Experimental and clinical data support effectiveness of perioperative radiotherapy to prevent heterotopic ossification after hip surgery or trauma. Since 1987, two prospectively randomized trials were performed in patients with high-risk factors to develop heterotopic ossification: the first (HOP 1) to assess the prophylactic efficacy of postoperative low vs. medium dose radiotherapy, and the second (HOP 2) to assess the prophylactic efficacy of pre vs. postoperative radiotherapy. Methods and Material: 410 patients with high risk to develop heterotopic ossifications about the hip following hip surgery were recruited. Between June 1987 and June 1992, 249 patients were randomized in HOP 1 to postoperative 'low dose' (5 x 2 Gy; total: 10 Gy) or 'medium dose' (5 x 3.5 Gy; total: 17.5 Gy) radiotherapy. Between July 1992 and December 1995, 161 patients were randomized in HOP 2 to either 1 x 7 Gy preoperatively (≤4 h before surgery) or 5 x 3.5 Gy (total: 17.5 Gy) postoperatively (≤96 h after surgery). With exception of age and type of implant (cemented vs. uncemented prosthesis) all confounding patient variables (gender, prior surgery) and predisposing risk factors were similarly distributed between both trials and treatment arms. Portals encompassed the peri acetabular and intertrochanteric soft tissues. Radiographs were obtained prior and immediately after surgery and at least 6 months after surgery to assess the extent of ectopic bone formation about the hip. Modified Brooker grading was used to score the extent of heterotopic ossification. Harris scoring was applied to evaluate the functional hip status. If the scores decreased from immediate post or preoperative status, respectively, to the last follow-up, radiological or functional failures were assumed. Results: Effective prophylaxis was achieved in 227 (91%) hips of HOP 1 and in 142 (88%) of HOP 2. In HOP 1, 15 (11%) radiological failures were observed in the low-dose group compared to 7 (6%) in the

  5. Is imatinib still the best choice as first-line oral TKI

    Directory of Open Access Journals (Sweden)

    Shweta Bansal

    2014-01-01

    Full Text Available Targeted therapy is the buzz word these days. A decade back the emergence of tyrosine kinase inhibitor Imatinib on the horizon, as the targeted therapy, had captured the imagination of everyone in the field of cancer. It is encouraging to see a large number of patients getting relief from deadly CML disease and leading a good quality of life with the help of this drug. However, sky is not the limit and now we have second and third generation tyrosine kinase inhibitors. I still remember the sagacious smile on the face of late Dr. John Goldman, when I asked him about his preferred choice and he replied and I quote "this is going to be the debate of the decade." Here I take the opportunity to contribute to this debate. I have scrutinized various aspects of the three TKIs, now recommended, for the treatment of CML. I`m still convinced it is too early to shift our practice completely towards 2G TKI as more time is required to make a clear recommendation.

  6. The novel oral imatinib microemulsions: physical properties, cytotoxicity activities and improved Caco-2 cell permeability.

    Science.gov (United States)

    Gundogdu, Evren; Karasulu, Hatice Yesim; Koksal, Cinel; Karasulu, Ercüment

    2013-01-01

    The objective of this study was to formulate imatinib (IM) loaded to water-in-oil (w/o) microemulsions as an alternative formulation for cancer therapy and to evaluate the cytotoxic effect of microemulsions Caco-2 and MCF-7. Moreover, permeability studies were also performed with Caco-2 cells. W/o microemulsion systems were developed by using pseudo-ternary phase diagram. According to cytotoxicity studies, all formulations did not exert a cytotoxic effect on Caco-2 cells. Furthermore, all formulations had a significant cytotoxic effect on MCF-7 cells and the cytotoxic effect of M3IM was significantly more than that of other microemulsions and IM solution (p < 0.05). The permeability studies of IM across Caco-2 cells showed that permeability value from apical to basolateral was higher than permeability value of other formulations. In conclusion, the microemulsion formulations as a drug carrier, especially M3IM formulation, may be used as an effective alternative breast cancer therapy for oral delivery of IM.

  7. Aplasia irreversible por el tratamiento con mesilato de Imatinib en una leucemia mieloide crónica: Presentación de un caso Irreversible aplasia due to the treatment with imatinib mesilate in a chronic myeloid leukemia: A case report

    Directory of Open Access Journals (Sweden)

    Olga Agramonte Llanes

    2007-04-01

    Full Text Available Se presenta una paciente de 45 años de edad diagnosticada en marzo de 1984 como una leucemia mieloide crónica Ph + , BCR/ABL positivo, que llevó tratamiento con busulfán, hidroxiurea, interferón y arabinósido de citosina durante 15 años. En marzo del 2003 se diagnosticó fase de transformación y en abril se comenzó la administración de Imatinib en dosis de 600mg diarios. Evolutivamente presentó dolores óseos ligeros, edema palpebral y en el día 35 pancitopenia severa, que provocó la suspensión del tratamiento. Se tomaron muestras para medulograma y biopsia de médula ósea y se diagnosticó una aplasia medular severa. Se administró tratamiento con antibioticoterapia de amplio espectro, hemoderivados y factor estimulador de colonias granulocíticas. A pesar de estas medidas terapéuticas, la paciente falleció a los 46 días de suspendido el tratamiento con Imatinib, con un cuadro clínico de aplasia medular irreversible y distrés respiratorio, complicaciones atribuibles al ImatinibA 45-year-old female patient who was diagnosed chronic myeloid leukemia Ph+ in March 1984, and had treatment with busulfan, hydroxyurea, interferon and cytosine arabinoside during 15 years is presented. In March 2003, the transformation stage was diagnosed and, in April, she began to receive imatinib at daily doses of 600 mg. Evolutively, she had mild bone pain, palpebral edema and, on the 35th day, severe pancytopenia that caused the suspension of the treatment. Bone marrow samples were taken by aspiration and biopsy, and a severe medular aplasia was diagnosed. Treatment with wide-spectrum antibiotic therapy, hemoderivates, and granulocyte colony-stimulating factor was applied. In spite of these therapeutic measures, the patient died 46 days after interrupting the treatment with imatinib, with a clinical picture of irreversible medular aplasia and respiratory distress, complications attributable to Imatinib

  8. Falla cardiaca asociada con el uso de imatinib mesilato: Reporte de un caso Heart failure associated to imatinib mesylate use: Case report

    Directory of Open Access Journals (Sweden)

    Clara Saldarriaga

    2008-12-01

    Full Text Available La cardiotoxicidad por medicamentos es un evento cada vez más frecuente en la práctica clínica diaria. Inhibidores de la proteína de fusión Brc/Abl como el imatinib mesilato, son una nueva herramienta para el tratamiento de algunas neoplasias hematológicas, en especial de la leucemia mieloide crónica. Sin embargo, en la literatura se reporta desarrollo de cardiotoxicidad a causa de este medicamento. Se presenta el caso de una mujer joven con corazón de estructura sana quien desarrolla cardiotoxicidad por imatinib pocas semanas después de iniciarlo.Cardiotoxicity due to drugs has become a frequent event in the daily clinical practice. Fusion protein Brc/Abl inhibitors such as imatinib mesylate constitute a new tool for the treatment of some hematogical neoplasias, especially chronic myeloid leukemia. Nevertheless, there have been reports in the literature regarding imatinib mesylate toxicity. We present the case of a young woman with a structurally healthy heart who developed cardiotoxicity with imatinib few weeks after its initiation.

  9. Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

    Science.gov (United States)

    Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

    2016-01-01

    The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

  10. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

    International Nuclear Information System (INIS)

    Schaefer, Inga-Marie; Hornick, Jason L.; Barysauskas, Constance M.; Raut, Chandrajit P.; Patel, Sagar A.; Royce, Trevor J.; Fletcher, Christopher D.M.; Baldini, Elizabeth H.

    2017-01-01

    Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.

  11. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, Inga-Marie; Hornick, Jason L. [Department of Pathology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Barysauskas, Constance M. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Raut, Chandrajit P. [Division of Surgical Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Patel, Sagar A.; Royce, Trevor J. [Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Fletcher, Christopher D.M. [Department of Pathology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2017-06-01

    Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.

  12. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score.

    Science.gov (United States)

    Schaefer, Inga-Marie; Hornick, Jason L; Barysauskas, Constance M; Raut, Chandrajit P; Patel, Sagar A; Royce, Trevor J; Fletcher, Christopher D M; Baldini, Elizabeth H

    2017-06-01

    To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Population pharmacokinetics of imatinib mesylate and its metabolite in children and young adults.

    Science.gov (United States)

    Menon-Andersen, Divya; Mondick, John T; Jayaraman, Bhuvana; Thompson, Patrick A; Blaney, Susan M; Bernstein, Mark; Bond, Mason; Champagne, Martin; Fossler, Michael J; Barrett, Jeffrey S

    2009-01-01

    Imatinib mesylate (Gleevec) is a small molecule tyrosine kinase inhibitor approved for use in the management of chronic myeloid leukemia in adults and children and in gastrointestinal stromal tumors in adults. Population pharmacokinetic (PPK) studies evaluating the effect of population covariates on the pharmacokinetics of imatinib and its active metabolite have been developed in adults with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). However, this still remains to be described in children. The objectives of the analysis were to develop a PPK model of imatinib and its active metabolite, CGP74588, to describe exposure in children and young adults and to identify covariates that are predictors of variability in disposition. Plasma concentrations from 26 subjects with Philadelphia (Ph+) leukemia (Phase I study) and 15 subjects with refractory solid tumors (Phase II study), who received oral imatinib at doses ranging from 260 to 570 mg/m(2), were available for the PPK analysis in NONMEM. Blood samples were drawn prior to dosing and over 24-48 h on days 1 and 8 of the studies. Covariates studied included weight, age, albumin, alanine aminotransferase and the study population. The pharmacokinetics of imatinib and CGP 74588 were well described by one and two compartment models, respectively. Total body weight was the only covariate found to significantly affect Cl/F and V/F. The final imatinib-CGP 74588 model is summarized as follows: CL/F (imatinib) (L/h) = 10.8 x (WT/70)(0.75), V/F (imatinib) (L) = 284 x (WT/70) and D1(duration of zero order absorption,imatinib) (h) = 1.67 and CL/F (CGP 74588) (L/h) = 9.65 x (WT/70)(0.75), V1/F (CGP 74588) (L) = 11.6 x (WT/70), Q (CGP 74588) (L/h) = 2.9 x (WT/70)(0.75) and V2/F (CGP 74588) (L) = 256*(WT/70). Model evaluation indicated that the final model was robust and satisfactory. Current imatinib dosing guidelines in pediatrics is based on the achievement of exposures consistent with doses known to be

  14. Preoperative therapy with pazopanib in high-risk soft tissue sarcoma: a phase II window-of-opportunity study by the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS).

    Science.gov (United States)

    Ronellenfitsch, Ulrich; Dimitrakopoulou-Strauss, Antonia; Jakob, Jens; Kasper, Bernd; Nowak, Kai; Pilz, Lothar R; Attenberger, Ulrike; Gaiser, Timo; Egerer, Gerlinde; Fröhling, Stefan; Derigs, Hans-Günter; Schwarzbach, Matthias; Hohenberger, Peter

    2016-01-06

    For resectable soft tissue sarcoma (STS), radical surgery, usually combined with radiotherapy, is the mainstay of treatment and the only potentially curative modality. Since surgery is often complicated by large tumour size and extensive tumour vasculature, preoperative treatment strategies with the aim of devitalising the tumour are being explored. One option is treatment with antiangiogenic drugs. The multikinase inhibitor pazopanib, which possesses pronounced antiangiogenic effects, has shown activity in metastatic and unresectable STS, but has so far not been tested in the preoperative setting. This open-label, multicentre phase II window-of-opportunity trial assesses pazopanib as preoperative treatment of resectable STS. Participants receive a 21-day course of pazopanib 800 mg daily during wait time for surgery. Major eligibility criteria are resectable, high-risk adult STS of any location, or metachronous solitary STS metastasis for which resection is planned, and adequate organ function and performance status. The trial uses an exact single-stage design. The primary end point is metabolic response rate (MRR), that is, the proportion of patients with >50% reduction of the mean standardised uptake value (SUVmean) in post-treatment compared to pre-treatment fluorodeoxyglucose positron emission tomography CT. The MRR below which the treatment is considered ineffective is 0.2. The MRR above which the treatment warrants further exploration is 0.4. With a type I error of 5% and a power of 80%, the sample size is 35 evaluable patients, with 12 or more responders as threshold. Main secondary end points are histopathological and MRI response, resectability, toxicity, recurrence-free and overall survival. In a translational substudy, endothelial progenitor cells and vascular epithelial growth factor receptor are analysed as potential prognostic and predictive markers. Approval by the ethics committee II, University of Heidelberg, Germany (2012-019F-MA), German Federal

  15. Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

    Science.gov (United States)

    Reardon, David A; Egorin, Merrill J; Quinn, Jennifer A; Rich, Jeremy N; Rich, Jeremy N; Gururangan, Sridharan; Gururangan, Idharan; Vredenburgh, James J; Desjardins, Annick; Sathornsumetee, Sith; Provenzale, James M; Herndon, James E; Dowell, Jeannette M; Badruddoja, Michael A; McLendon, Roger E; Lagattuta, Theodore F; Kicielinski, Kimberly P; Dresemann, Gregor; Sampson, John H; Friedman, Allan H; Salvado, August J; Friedman, Henry S

    2005-12-20

    We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

  16. A radioprotective effect of imatinib (Gleevec registered) in human squamous carcinoma cells

    International Nuclear Information System (INIS)

    Bartkowiak, D.; Hipp, P.R.; Roettinger, E.M.; Mendonca, M.S.

    2007-01-01

    Purpose: To study the radiation response-modifying effect of imatinib (Gleevec registered ) in a squamous cell carcinoma line, PECA. Patients and Methods: Cytotoxicity was determined by colony forming and multiplying capacity. Drug stability was shown by HPLC. Multidrug resistance phenotype was studied by rhodamine-123 efflux. Cell-cycle responses were measured by flow cytometry. Homologous recombination repair was determined by Rad51 immunohistochemistry. Results: Inactivating 50% of the PECA cells required approximately 7 μM imatinib. The drug did not decay nor was it degraded during test periods. Drug efflux occurred only to a minor extent. Multiplying capacity but not survival fractions revealed a radioprotective effect of imatinib. There were only minor cell-cycle alterations in the presence of imatinib but the rate of Rad51-positive repair foci was significantly increased. Conclusion: PECA cells apparently lack a highly specific target for imatinib. In cells surviving at high drug concentrations, imatinib may exert a radioprotective effect on multiplying capacity by inducing DNA repair. Under prolonged exposure, drug-resistant cells may show an accelerated recovery from acute or delayed radiation damage. (orig.)

  17. Could imatinib replace surgery in esophageal gastrointestinal stromal tumor

    International Nuclear Information System (INIS)

    Al-Salam, Suhail N.; El-Teraifi, Hassan A.; Taha, Mazen S.

    2006-01-01

    Gastrointestinal stromal tumors (GISTs) are cellular spindle, or epithelioid tumors that occur in the stomach, intestine and rarely in the esophagus. A 61-years-old man was complaining of resistant dry cough with dysphagia for one month duration. Upper gastrointestinal tract endoscopic examination showed a polypoid mass 30 cm from the incisors obstructing 50% of the lumen, where multiple biopsies were taken. Magnetic resonance imaging (MRI) showed a mass in the wall of the esophagus extending into the thoracic cavity. Histologically, the stained sections with routine hematoxylin and eosin as well as the immunohistochemical stainsfor CD117, CD34, S100, vimentin and smooth muscle actin confirmed the diagnosis of esophageal GIST. The patient was treated with imatinib 400mg/day. There was a dramatic reduction in the size of the tumor with successful improvement of his symptoms after 2 months of treatment, which was confirmed by reapeated upper GIT endoscopy, and MRI. (author)

  18. Leucemia Mielóide Crônica: causas de falha do tratamento com mesilato de imatinibe Chronic Myeloid Leukemia: causes of treatment failure with imatinib

    Directory of Open Access Journals (Sweden)

    Katia B. B. Pagnano

    2008-04-01

    Full Text Available O mesilato de imatinibe (MI é atualmente o tratamento de escolha da Leucemoa Mielóide Crônica (LMC, mas, apesar dos excelentes resultados, não é capaz de erradicar completamente a doença, podendo ocorrer resistência ao tratamento. O mecanismo mais conhecido de resistência é o desenvolvimento de mutações do BCR-ABL, que impedem a ação ligação adequada do imatinibe à quinase, além de amplificação gênica e evolução clonal. No entanto, há uma série de outros mecanismos envolvidos e ainda pouco estudados, como alterações na absorção, efluxo e influxo de droga para o interior das células. Devem-se também considerar outros fatores, como aderência ao tratamento e uso de medicamentos concomitantes que podem interferir com imatinibe, diminuindo sua ação. O entendimento desses mecanismos poderá contribuir no desenvolvimento de novas estratégias para o tratamento dos casos resistentes.Imatinib is currently the treatment of choice of CML, but despite of the excellent results, it is not able to completely eradicate the disease and resistance may occur. The most studied mechanism is the presence of ABL kinase mutations that interfere with imatinib binding and action, gene amplification and clonal evolution. However, there are other mechanisms involved and less studied such as drug absorption and influx and efflux of imatinib. Besides the true causes of resistance, compliance is always a concern and also drug interaction should be checked. An understanding of these mechanisms will certainly contribute to develop new strategies for the treatment of resistant cases.

  19. Molecular response to imatinib & its correlation with mRNA expression levels of imatinib influx & efflux transporters in patients with chronic myeloid leukaemia in chronic phase

    Directory of Open Access Journals (Sweden)

    Hemant Malhotra

    2015-01-01

    Full Text Available Background & objectives: Imatinib is the standard first-line treatment for chronic myeloid leukaemia (CML patients. About 20 to 30 per cent patients develop resistance to imatinib and fail imatinib treatment. One of the mechanisms proposed is varying expression levels of the drug transporters. This study was aimed to determine the expression levels of imatinib transporter genes (OCT1, ABCB1, ABCG2 in CML patients and to correlate these levels with molecular response. Methods: Sixty three CML chronic phase patients who were on 400 mg/day imatinib for more than two years were considered for gene expression analysis study for OCT1, ABCB1 and ABCG2 genes. These were divided into responders and non-responders. The relative transcript expression levels of the three genes were compared between these two categories. The association between the expression values of these three genes was also determined. Results: No significant difference in the expression levels of OCT1, ABCB1 and ABCG2 was found between the two categories. The median transcript expression levels of OCT1, ABCB1 and ABCG2 genes in responders were 26.54, 10.78 and 0.64 versus 33.48, 7.09 and 0.53 in non-responders, respectively. A positive association was observed between the expression of the ABCB1 and ABCG2 transporter genes (r=0.407, P<0.05 while no association was observed between the expression of either of the ABC transporter genes with the OCT1 gene. Interpretation & conclusions: Our findings demonstrated that the mRNA expression levels of imatinib transporter genes were not correlated with molecular response in CML patients. Further studies need to be done on a large sample of CML patients to confirm these findings.

  20. Towards a Molecular Understanding of the Link between Imatinib Resistance and Kinase Conformational Dynamics.

    Directory of Open Access Journals (Sweden)

    Silvia Lovera

    2015-11-01

    Full Text Available Due to its inhibition of the Abl kinase domain in the BCR-ABL fusion protein, imatinib is strikingly effective in the initial stage of chronic myeloid leukemia with more than 90% of the patients showing complete remission. However, as in the case of most targeted anti-cancer therapies, the emergence of drug resistance is a serious concern. Several drug-resistant mutations affecting the catalytic domain of Abl and other tyrosine kinases are now known. But, despite their importance and the adverse effect that they have on the prognosis of the cancer patients harboring them, the molecular mechanism of these mutations is still debated. Here by using long molecular dynamics simulations and large-scale free energy calculations complemented by in vitro mutagenesis and microcalorimetry experiments, we model the effect of several widespread drug-resistant mutations of Abl. By comparing the conformational free energy landscape of the mutants with those of the wild-type tyrosine kinases we clarify their mode of action. It involves significant and complex changes in the inactive-to-active dynamics and entropy/enthalpy balance of two functional elements: the activation-loop and the conserved DFG motif. What is more the T315I gatekeeper mutant has a significant impact on the binding mechanism itself and on the binding kinetics.

  1. Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo.

    Science.gov (United States)

    Venalis, Paulius; Maurer, Britta; Akhmetshina, Alfiya; Busch, Nicole; Dees, Clara; Stürzl, Michael; Zwerina, Jochen; Jüngel, Astrid; Gay, Steffen; Schett, Georg; Distler, Oliver; Distler, Jörg H W

    2009-10-01

    Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries and tissue fibrosis. Imatinib exerts potent anti-fibrotic effects and is currently evaluated in clinical trials. The aim of the present study was to exclude that the anti-fibrotic effects of imatinib are complicated by inhibitory effects on endothelial cell functions, which might augment vascular disease in SSc. Endothelial cells and mice were treated with pharmacologically relevant concentrations of imatinib. The expression of markers of vascular activation was assessed with real-time PCR. Proliferation was analysed with the cell counting experiments and the MTT assay. Apoptosis was quantified with caspase 3 assays, annexin V in vitro and with TUNEL staining in vivo. Migration was studied with scratch and transwell assays. Tube forming was investigated with the matrigel assay. Imatinib did not alter the expression of markers of vascular activation. Imatinib did not increase the percentage of annexin V positive cells or the activity of caspase 3. No reduction in proliferation or metabolic activity of endothelial cells was observed. Imatinib did not affect migration of endothelial cells and did not reduce the formation of capillary tubes. Consistent with the in vitro data, no difference in the number of apoptotic endothelial cells was observed in vivo in mice treated with imatinib. Imatinib does not inhibit activation, viability, proliferation, migration or tube forming of endothelial cells in vitro and in vivo. Thus, treatment with imatinib might not augment further endothelial cell damage in SSc.

  2. Effects of imatinib mesylate on the pharmacokinetics of paracetamol (acetaminophen) in Korean patients with chronic myelogenous leukaemia.

    Science.gov (United States)

    Kim, Dong-Wook; Tan, Eugene Y; Jin, Yu; Park, Sahee; Hayes, Michael; Demirhan, Eren; Schran, Horst; Wang, Yanfeng

    2011-02-01

    The major objective of the present study was to investigate the effect of imatinib on the pharmacokinetics of paracetamol in patients with chronic myelogenous leukaemia (CML). Patients (n = 12) received a single oral dose of acetaminophen 1000 mg on day 1 (control). On days 2-8, imatinib 400 mg was administered daily. On day 8 (treatment), another 1000 mg dose of paracetamol was administered 1 h after the morning dose of imatinib 400 mg. Blood and urine samples were collected for bioanalytical analyses. The area under the plasma concentration-time curve (AUC) for paracetamol, paracetamol glucuronide and paracetamol sulphate under control conditions was similar to that after treatment with imatinib; the 90% confidence interval of the log AUC ratio was within 0.8 to 1.25. Urinary excretion of paracetamol, paracetamol glucuronide and paracetamol sulphate was also unaffected by imatinib. The pharmacokinetics of paracetamol and imatinib in Korean patients with CML were similar to previous pharmacokinetic results in white patients with CML. Co-administration of a single dose of paracetamol and multiple doses of imatinib was well tolerated and safety profiles were similar to those of either drug alone. The pharmacokinetics of paracetamol and its major metabolites in the presence of imatinib were similar to those of the control conditions and the combination was well tolerated. These findings suggest that imatinib can be safely administered with paracetamol without dose adjustment of either drug. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  3. [Preoperative structured patient education].

    Science.gov (United States)

    Lamarche, D

    1993-04-01

    This article describes the factors that motivated the nursing staff of the cardiac surgery unit at the Royal Victoria Hospital in Montreal, to revise their preoperative teaching program. The motivating factors described are the length of the preoperative waiting period; the level of preoperative anxiety; the decreased length of hospital stay; the dissatisfaction of the nursing staff with current patient teaching practices; and the lack of available resources. The reorganization of the teaching program was based upon the previously described factors combined with a review of the literature that demonstrated the impact of preoperative anxiety, emotional support and psycho-educational interventions upon the client's recovery. The goals of the new teaching program are to provide the client and the family with cognitive and sensory information about the client's impending hospitalization, chronic illness and necessary lifestyle modifications. The program consists of a system of telephone calls during the preoperative waiting period; a videotape viewing; a tour of the cardiac surgery unit; informal discussion groups; and the availability of nursing consultation to decrease preoperative anxiety. The end result of these interventions is more time for client support and integration of necessary information by the client and family. This kind of program has the potential to provide satisfaction at many levels by identifying client's at risk; increasing client knowledge; increasing support; decreasing anxiety during the preoperative waiting period; and decreasing the length of hospital stay. The nursing staff gained a heightened sense of accomplishment because the program was developed according to the nursing department's philosophy, which includes primary nursing.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy

    International Nuclear Information System (INIS)

    Krainick-Strobel, Ute E; Lichtenegger, Werner; Wallwiener, Diethelm; Tulusan, Augustinus H; Jänicke, Fritz; Bastert, Gunther; Kiesel, Ludwig; Wackwitz, Birgit; Paepke, Stefan

    2008-01-01

    In recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3–4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established. This study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4–8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed. Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56–85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage ≥ T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and > 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were mastectomy candidates

  5. Immediate preoperative enteral nutrition (preoperative enteral nutrition

    Directory of Open Access Journals (Sweden)

    Lađević Nebojša

    2017-01-01

    Full Text Available Nutritional support of surgical patients is a necessary part of the treatment. It alone cannot cure the disease but it significantly affects the recovery of patients and supports surgical interventions. Patients in malnutrition have shown to have significantly more postoperative infectious and non-infectious complications. This significantly prolongs treatment time and increases costs. However, there is one fact that cannot be expressed in money, which is the patient's impression of the surgical intervention. Adequate preoperative patient support, based on the intake of liquid nutritive solutions, reduces preoperative stress and deflects the metabolic response. Now, it is recommended for adults and children older than one year to drink clear liquid up to 2 hours before induction in anesthesia. Appropriate enteral nutrition has a significant place in the postoperative recovery of patients. Enteral nutrition is reducing complications, mainly infectious complications because the function of the digestive system as one large immune system is preserved. Perioperative enteral nutrition is a necessary part of the modern treatment of surgical patients. In addition to the significant effect on the occurrence of postoperative complications, it is also important that this type of diet improves the psychological status of patients.

  6. Efeitos adversos e resposta citogenética em pacientes com leucemia mieloide crônica tratados com imatinibe Adverse events and cytogenetc response in patients with chronic myeloid leukemia treated with imatinib

    Directory of Open Access Journals (Sweden)

    Tatiana F. Alvarenga

    2010-01-01

    pacientes.Chronic myeloid leukemia (CML is a clonal myeloproliferative disorder characterized cytogenetically by the Philadelphia chromosome (Ph. Therapeutic options of this disease are: hydroxyurea, interferon-a, allogeneic HSCT and more recently imatinib. This latter therapy demonstrated efficacy in the treatment of CML, particularly in the chronic phase. However some studies have demonstrated that there are additional chromosomal alterations related to resistance while others have reported undesirable clinical manifestations during imatinib therapy such as headache, nausea and vomiting. Because of the importance of this new molecular target therapy, it may be necessary to analyze the response of this treatment in respect to the quality of life of patients. The aim of this study was to analyze the clinical manifestations and the cytogenetic response during imatinib therapy in fifty-one patients with CML who had previously been treated using interferon-a. Cytogenetic analysis was performed in bone marrow cells using GTG-banding. The commonest clinical manifestations were mild to moderate: headache (37%, nausea (37%, vomiting (33% and edema (33%. Patients that achieved major cytogenetic response had a significantly longer median survival than patients without response (p=0.007. Eight patients evolved to death; none of them exhibited cytogenetic responses to imatinib. Our results show the importance of the clinical (analyzing the degree of tolerance to the drug and cytogenetic follow-up, where the presence of additional chromosomal alterations showed a distinct biological pattern that is not identifiable by molecular techniques, and so cytogenetic analysis is an important tool for the diagnosis and monitoring of this group of patientss.

  7. Preoperative Chemotherapy Versus Preoperative Chemoradiotherapy for Stage III (N2) Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, Kristin [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States); Chino, Junzo P [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States); Marks, Lawrence B [Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC (United States); Ready, Neal [Department of Medicine, Division of Medical Oncology, Duke University of Medical Center, Durham, NC (United States); D' Amico, Thomas A [Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University of Medical Center, Durham, NC (United States); Clough, Robert W; Kelsey, Chris R [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States)

    2009-12-01

    Purpose: To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non-small-cell lung cancer. Methods and Materials: This retrospective study analyzed all patients with pathologically confirmed Stage III (N2) non-small-cell lung cancer who initiated preoperative ChT or ChT-RT at Duke University between 1995 and 2006. Mediastinal pathologic complete response (pCR) rates were compared using a chi-square test. The actuarial overall survival, disease-free survival, and local control were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was also performed. Results: A total of 101 patients who initiated preoperative therapy with planned resection were identified. The median follow-up was 20 months for all patients and 38 months for survivors. The mediastinal lymph nodes were reassessed after preoperative therapy in 88 patients (87%). Within this group, a mediastinal pCR was achieved in 35% after preoperative ChT vs. 65% after preoperative ChT-RT (p = 0.01). Resection was performed in 69% after ChT and 84% after ChT-RT (p = 0.1). For all patients, the overall survival, disease-free survival, and local control rate at 3 years was 40%, 27%, and 66%, respectively. No statistically significant differences were found in the clinical endpoints between the ChT and ChT-RT subgroups. On multivariate analysis, a mediastinal pCR was associated with improved disease-free survival (p = 0.03) and local control (p = 0.03), but not overall survival (p = 0.86). Conclusion: Preoperative ChT-RT was associated with higher mediastinal pCR rates but not improved survival.

  8. Preoperative Chemotherapy Versus Preoperative Chemoradiotherapy for Stage III (N2) Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Higgins, Kristin; Chino, Junzo P.; Marks, Lawrence B.; Ready, Neal; D'Amico, Thomas A.; Clough, Robert W.; Kelsey, Chris R.

    2009-01-01

    Purpose: To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non-small-cell lung cancer. Methods and Materials: This retrospective study analyzed all patients with pathologically confirmed Stage III (N2) non-small-cell lung cancer who initiated preoperative ChT or ChT-RT at Duke University between 1995 and 2006. Mediastinal pathologic complete response (pCR) rates were compared using a chi-square test. The actuarial overall survival, disease-free survival, and local control were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was also performed. Results: A total of 101 patients who initiated preoperative therapy with planned resection were identified. The median follow-up was 20 months for all patients and 38 months for survivors. The mediastinal lymph nodes were reassessed after preoperative therapy in 88 patients (87%). Within this group, a mediastinal pCR was achieved in 35% after preoperative ChT vs. 65% after preoperative ChT-RT (p = 0.01). Resection was performed in 69% after ChT and 84% after ChT-RT (p = 0.1). For all patients, the overall survival, disease-free survival, and local control rate at 3 years was 40%, 27%, and 66%, respectively. No statistically significant differences were found in the clinical endpoints between the ChT and ChT-RT subgroups. On multivariate analysis, a mediastinal pCR was associated with improved disease-free survival (p = 0.03) and local control (p = 0.03), but not overall survival (p = 0.86). Conclusion: Preoperative ChT-RT was associated with higher mediastinal pCR rates but not improved survival.

  9. Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation.

    Science.gov (United States)

    Loveman, E; Cooper, K; Bryant, J; Colquitt, J L; Frampton, G K; Clegg, A

    2012-01-01

    The present report was commissioned as a supplement to an existing technology assessment report produced by the Peninsula Technology Assessment Group (PenTAG), which evaluated the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in patients who are either resistant or intolerant to standard-dose imatinib. This report evaluates the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and high-dose imatinib within their licensed indications for the treatment of people with chronic myeloid leukaemia (CML) who are resistant to standard-dose imatinib. Bibliographic databases were searched from inception to January 2011, including The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences were searched, and experts were contacted to identify additional published and unpublished references. This report includes systematic reviews of clinical effectiveness and cost-effectiveness studies, an independent appraisal of information submitted by drug manufacturers to the National Institute for Health and Clinical Excellence (NICE), an independent appraisal of the PenTAG economic evaluation, and new economic analyses adapting the PenTAG economic model. Standard systematic procedures involving two reviewers to maintain impartiality and transparency, and to minimise bias, were conducted. Eleven studies met the inclusion criteria. Four of these studies included new data published since the PenTAG report; all of these were in chronic-phase CML. No relevant studies on the clinical effectiveness of nilotinib were found. The clinical effectiveness studies on dasatinib [one arm of a randomised controlled trial (RCT)] and high-dose imatinib (one arm of a RCT and three single-arm cohort studies) had major methodological limitations. These limitations precluded a comparison of the different arms within the RCT. Data from the studies are

  10. Protonation effects on the UV/Vis absorption spectra of imatinib: a theoretical and experimental study.

    Science.gov (United States)

    Grante, Ilze; Actins, Andris; Orola, Liana

    2014-08-14

    An experimental and theoretical investigation of protonation effects on the UV/Vis absorption spectra of imatinib showed systematic changes of absorption depending on the pH, and a new absorption band appeared below pH 2. These changes in the UV/Vis absorption spectra were interpreted using quantum chemical calculations. The geometry of various imatinib cations in the gas phase and in ethanol solution was optimized with the DFT/B3LYP method. The resultant geometries were compared to the experimentally determined crystal structures of imatinib salts. The semi-empirical ZINDO-CI method was employed to calculate the absorption lines and electronic transitions. Our study suggests that the formation of the extra near-UV absorption band resulted from an increase of imatinib trication concentration in the solution, while the rapid increase of the first absorption maximum could be attributed to both the formation of imatinib trication and tetracation. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Chronic myeloid leukemia patients in Tunisia: epidemiology and outcome in the imatinib era (a multicentric experience).

    Science.gov (United States)

    Ben Lakhal, Raihane; Ghedira, Hela; Bellaaj, Hatem; Ben Youssef, Yosra; Menif, Samia; Manai, Zeineb; Bedoui, Manel; Lakhal, Amel; M'Sadek, Fehmi; Elloumi, Moez; Khélif, Abderrahmane; Ben Romdhane, Neila; Laatiri, Mohamed Adnène; Ben Othmen, Tarek; Meddeb, Balkis

    2018-04-01

    Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome-overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)-were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3-85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3-51), 18 months (3-72), and 24 months (3-100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS

  12. [Preoperative fasting. An update].

    Science.gov (United States)

    Spies, C D; Breuer, J P; Gust, R; Wichmann, M; Adolph, M; Senkal, M; Kampa, U; Weissauer, W; Schleppers, A; Soreide, E; Martin, E; Kaisers, U; Falke, K J; Haas, N; Kox, W J

    2003-11-01

    In Germany the predominant standard of preoperative care for elective surgery is fasting after midnight, with the aim of reducing the risk of pulmonary aspiration. However, for the past several years the scientific evidence supporting such a practice has been challenged. Experimental and clinical studies prove a reliable gastric emptying within 2 h suggesting that, particularly for limited intake of clear fluids up to 2 h preoperatively, there would be no increased risk for the patient. In addition, the general incidence of pulmonary aspiration during general anaesthesia (before induction, during surgery and during recovery) is extremely low, has a good prognosis and is more a consequence of insufficient airway protection and/or inadequate anaesthetic depth rather than due to the patient's fasting state. Therefore, primarily to decrease perioperative discomfort for patients, several national anaesthesia societies have changed their guidelines for preoperative fasting. They recommend a more liberal policy regarding per os intake of both liquid and solid food, with consideration of certain conditions and contraindications. The following article reviews the literature and gives an overview of the scientific background on which the national guidelines are based. The intention of this review is to propose recommendations for preoperative fasting regarding clear fluids for Germany as well.

  13. The conformational control inhibitor of tyrosine kinases DCC-2036 is effective for imatinib-resistant cells expressing T674I FIP1L1-PDGFRα.

    Directory of Open Access Journals (Sweden)

    Yingying Shen

    Full Text Available The cells expressing the T674I point mutant of FIP1-like-1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα in hypereosinophilics syndrome (HES are resistant to imatinib and some second-generation tyrosine kinase inhibitors (TKIs. There is a desperate need to develop therapy to combat this acquired drug resistance. DCC-2036 has been synthesized as a third-generation TKI to combat especially the Bcr-Abl T315I mutant in chronic myeloid leukemia. This study evaluated the effect of DCC-2036 on FIP1L1-PDGFRα-positive cells, including the wild type (WT and the T674I mutant. The in vitro effects of DCC-2036 on the PDGFRα signal pathways, proliferation, cell cycling and apoptosis of FIP1L1-PDGFRα-positive cells were investigated, and a nude mouse xenograft model was employed to assess the in vivo antitumor activity. We found that DCC-2036 decreased the phosphorylated levels of PDGFRα and its downstream targets without apparent effects on total protein levels. DCC-2036 inhibited proliferation, and induced apoptosis with MEK-dependent up-regulation of the pro-apoptotic protein Bim in FIP1L1-PDGFRα-positive cells. DCC-2036 also exhibited in vivo antineoplastic activity against cells with T674I FIP1L1-PDGFRα. In summary, FIP1L1-PDGFRα-positive cells are sensitive to DCC-2036 regardless of their sensitivity to imatinib. DCC-2036 may be a potential compound to treat imatinib-resistant HES.

  14. The predictive value of early molecular response in chronic myeloid leukaemia patients treated with imatinib in a single real-world medical centre in a developing country.

    Science.gov (United States)

    Bee, Ping Chong; Sekaran, Veera; Ng, Richard Rui Jie; Kweh, Ting Yi; Gan, Gin Gin

    2017-03-01

    The prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major molecular response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that early and deeper cytogenetic and molecular responses predict a better long-term outcome. This study aimed to analyse the relationship between early molecular response and clinical outcome in a real-life setting. This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia. A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients. Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients. Copyright: © Singapore Medical Association

  15. Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

    Directory of Open Access Journals (Sweden)

    Danielle Maria Camelo Cid

    2013-01-01

    Full Text Available Background: In the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. Objective: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. Methods: This retrospective study was based on information obtained from patients'records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC. All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. Results: The study population consisted of 100 patients who were mostly male (51% with ages rangingbetween 21 and 40 years (42%, from the countryside (59%, in the chronic phase (95%, with high-riskprognostic factors (40%; the prognosis of high risk was not associated with complete hematologic responseor complete cytogenetic response, but correlated to complete molecular response or major molecularresponse. Reticulin condensation was associated with complete hematologic response and completecytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. Thehigh adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. Conclusion: Significant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications.

  16. Interventions for preoperative smoking cessation

    DEFF Research Database (Denmark)

    Thomsen, Thordis; Villebro, Nete; Møller, Ann Merete

    2010-01-01

    a smoking cessation intervention, and measured preoperative and long-term abstinence from smoking and/or the incidence of postoperative complications. Data collection and analysis The authors independently assessed studies to determine eligibility. Results were discussed between the authors. Main results...... Eight trials enrolling a total of 1156 people met the inclusion criteria. One of these did not report cessation as an outcome. Two trials initiated multisession face to face counselling at least 6 weeks before surgery whilst six used a brief intervention. Nicotine replacement therapy (NRT) was offered......; pooled RR 10.76 (95% confidence interval (CI) 4.55 to 25.46, two trials) and RR 1.41 (95% CI 1.22 to 1.63, five trials) respectively. Four trials evaluating the effect on long-term smoking cessation found a significant effect; pooled RR 1.61 (95% CI 1.12 to 2.33). However, when pooling intensive...

  17. Pre-operative assessment of residual disease in locally advanced breast cancer patients: A sequential study by quantitative diffusion weighted MRI as a function of therapy.

    Science.gov (United States)

    Agarwal, Khushbu; Sharma, Uma; Sah, Rani G; Mathur, Sandeep; Hari, Smriti; Seenu, Vurthaluru; Parshad, Rajinder; Jagannathan, Naranamangalam R

    2017-10-01

    The potential of diffusion weighted imaging (DWI) in assessing pathologic response and surgical margins in locally advanced breast cancer patients (n=38) undergoing neoadjuvant chemotherapy was investigated. DWI was performed at pre-therapy (Tp0), after I (Tp1) and III (Tp3) NACT at 1.5T. Apparent diffusion coefficient (ADC) of whole tumor (ADC WT ), solid tumor (ADC ST ), intra-tumoral necrosis (ADC Nec ) was determined. Further, ADC of 6 consecutive shells (5mm thickness each) including tumor margin to outside tumor margins (OM1 to OM5) was calculated and the data analyzed to define surgical margins. Of 38 patients, 6 were pathological complete responders (pCR), 19 partial responders (pPR) and 13 were non-responders (pNR). Significant increase was observed in ADC ST and ADC WT in pCR and pPR following therapy. Pre-therapy ADC was significantly lower in pCR compared to pPR and pNR indicating the heterogeneous nature of tumor which may affect drug perfusion and consequently the response. ADC of outside margins (OM1, OM2, and OM3) was significantly different among pCR, pPR and pNR at Tp3 which may serve as response predictive parameter. Further, at Tp3, ADC of outside margins (OM1, OM2, and OM3) was significantly lower compared to that seen at Tp0 in pCR, indicating the presence of residual disease in these shells. Pre-surgery information may serve as a guide to define cancer free margins and the extent of residual disease which may be useful in planning breast conservation surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Preoperative [18F]-fluorodeoxyglucose positron emission tomography standardized uptake value of neck lymph nodes may aid in selecting patients with oral cavity squamous cell carcinoma for salvage therapy after relapse

    International Nuclear Information System (INIS)

    Liao, Chun-Ta; Huang, Shiang-Fu; Chen, I. How; Chang, Joseph Tung-Chieh; Wang, Hung-Ming; Ng, Shu-Hang; Hsueh, Chuen; Lee, Li-Yu.; Lin, Chih-Hung; Cheng, Ann-Joy; Yen, Tzu-Chen

    2009-01-01

    Relapse of tumours in patients with oral cavity squamous cell carcinoma (OSCC) is associated with a dismal outcome. In this prospective study, we sought to investigate the clinical significance of the preoperative maximal standardized uptake value (SUVmax) at the neck lymph nodes in selecting patients with OSCC for salvage therapy after relapse. Between 2002 and 2007, 108 patients with early relapse of OSCC (n=75) or late relapse of OSCC (n=33) were identified. Salvage therapy was performed in 47 patients. All patients underwent 2-deoxy-2[ 18 F]-fluoro-d-glucose positron emission tomography during the 2 weeks before surgery and neck dissection. All patients were followed for 12 months or more after surgery or until death. The optimal cut-off value for the neck lymph node SUVmax (SUVnodal-max) was selected according to the 5-year disease-specific survival (DSS) rate. Independent risk factors were identified by Cox regression analysis. The mean follow-up for all patients was 20.3 months (41.1 months for surviving patients). In the early relapse group, several prognostic factors were identified in univariate and multivariate analyses, including a SUVnodal-max value of ≥4.2. A scoring system based on univariate analysis was formulated. Patients with a score of 0 had a better 5-year DSS than those with scores of 1 or higher (58% vs. 5%, p=0.0003). In patients with late relapse, a SUVnodal-max value of ≥4.2 had the highest prognostic value for predicting the 5-year DSS (45% vs. 0%, p=0.0005). Among patients with relapsed OSCC, the SUVnodal-max value may aid in selecting patients for salvage therapy. (orig.)

  19. Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis.

    Science.gov (United States)

    Wahlgren, N; Thorén, M; Höjeberg, B; Käll, T-B; Laska, A-C; Sjöstrand, C; Höijer, J; Almqvist, H; Holmin, S; Lilja, A; Fredriksson, L; Lawrence, D; Eriksson, U; Ahmed, N

    2017-03-01

    Imatinib, a tyrosine kinase inhibitor, has been shown to restore blood-brain barrier integrity and reduce infarct size, haemorrhagic transformation and cerebral oedema in stroke models treated with tissue plasminogen activator. We evaluated the safety of imatinib, based on clinical and neuroradiological data, and its potential influence on neurological and functional outcomes. A phase II randomized trial was performed in patients with acute ischaemic stroke treated with intravenous thrombolysis. A total of 60 patients were randomly assigned to four groups [3 (active): 1 (control)]; the active treatment groups received oral imatinib for 6 days at three dose levels (400, 600 and 800 mg). Primary outcome was any adverse event; secondary outcomes were haemorrhagic transformation, cerebral oedema, neurological severity on the National Institutes of Health Stroke Scale (NIHSS) at 7 days and at 3 months and functional outcomes on the modified Rankin scale (mRS). Four serious adverse events were reported, which resulted in three deaths (one in the control group and two in the 400-mg dose group; one patient in the latter group did not receive active treatment and the other received two doses). Nonserious adverse events were mostly mild, resulting in full recovery. Imatinib ameliorated neurological outcomes with an improvement of 0.6 NIHSS points per 100 mg imatinib (P = 0.02). For the 800-mg group, the mean unadjusted and adjusted NIHSS improvements were 4 (P = 0.037) and 5 points (P = 0.012), respectively, versus controls. Functional independence (mRS 0-2) increased by 18% versus controls (61 vs. 79; P = 0.296). This phase II study showed that imatinib is safe and tolerable and may reduce neurological disability in patients treated with intravenous thrombolysis after ischaemic stroke. A confirmatory randomized trial is currently underway. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The

  20. The treatment of pediatric chronic myelogenous leukemia in the imatinib era

    Directory of Open Access Journals (Sweden)

    Jae Wook Lee

    2011-03-01

    Full Text Available Childhood chronic myelogenous leukemia (CML is a rare hematologic disease, with limited literature on the methods of treatment. Previously, allogeneic hematopoietic stem cell transplantation (HSCT was considered the only curative treatment for this disease. Treatment with imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase (TKI, has resulted in prolonged molecular response with limited drug toxicity. Imatinib is now implemented in the primary treatment regimen for children, but the paucity of evidence on its ability to result in permanent cure and the potential complications that may arise from long-term treatment with TKIs have prevented imatinib from superseding HSCT as the primary means of curative treatment in children. The results of allogeneic HSCT in children with CML are similar to those observed in adults; HSCT-related complications such as transplant-related mortality and graft-versus-host disease remain significant challenges. An overall consensus has been formed with regards to the need for HSCT in patients with imatinib resistance or those with advanced-phase disease. However, issues such as when to undertake HSCT in chronic-phase CML patients or how best to treat patients who have relapsed after HSCT are still controversial. The imatinib era calls for a reevaluation of the role of HSCT in the treatment of CML. Specific guidelines for the treatment of pediatric CML have not yet been formulated, underscoring the importance of prospective studies on issues such as duration of imatinib treatment, optimal timing of HSCT and the type of conditioning utilized, possible treatment preand post-HSCT, and the role of second-generation TKIs.

  1. Interventions for preoperative smoking cessation

    DEFF Research Database (Denmark)

    Møller, A; Villebro, N

    2005-01-01

    Smokers have a substantially increased risk of intra- and postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence. The preoperative period may be a well chosen time to offer smoking cessation interventions due to increased patient motivation....

  2. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

    OpenAIRE

    Reardon, D A; Dresemann, G; Taillibert, S; Campone, M; van den Bent, M; Clement, P; Blomquist, E; Gordower, L; Schultz, H; Raizer, J; Hau, P; Easaw, J; Gil, M; Tonn, J; Gijtenbeek, A

    2009-01-01

    textabstractBackground: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIA...

  3. Imatinib-loaded polyelectrolyte microcapsules for sustained targeting of BCR-ABL+ leukemia stem cells.

    Science.gov (United States)

    Palamà, Ilaria E; Leporatti, Stefano; de Luca, Emanuela; Di Renzo, Nicola; Maffia, Michele; Gambacorti-Passerini, Carlo; Rinaldi, Ross; Gigli, Giuseppe; Cingolani, Roberto; Coluccia, Addolorata M L

    2010-04-01

    The lack of sensitivity of chronic myeloid leukemia (CML) stem cells to imatinib mesylate (IM) commonly leads to drug dose escalation or early disease relapses when therapy is stopped. Here, we report that packaging of IM into a biodegradable carrier based on polyelectrolyte microcapsules increases drug retention and antitumor activity in CML stem cells, also improving the ex vivo purging of malignant progenitors from patient autografts. Microparticles/capsules were obtained by layer-by-layer (LbL) self-assembly of oppositely charged polyelectrolyte multilayers on removable calcium carbonate (CaCO(3)) templates and loaded with or without IM. A leukemic cell line (KU812) and CD34(+) cells freshly isolated from healthy donors or CML patients were tested. Polyelectrolyte microcapsules (PMCs) with an average diameter of 3 microm, fluorescently labelled multilayers sensitive to the action of intracellular proteases and 95-99% encapsulation efficiency of IM, were prepared. Cell uptake efficiency of such biodegradable carriers was quantified in KU812, leukemic and normal CD34(+) stem cells (range: 70-85%), and empty PMCs did not impact cell viability. IM-loaded PMCs selectively targeted CML cells, by promoting apoptosis at doses that exert only cytostatic effects by IM alone. More importantly, residual CML cells from patient leukapheresis products were reduced or eliminated more efficiently by using IM-loaded PMCs compared with freely soluble IM, with a purging efficiency of several logs. No adverse effects on normal CD34(+) stem-cell survival and their clonogenic potential was noticed in long-term cultures of hematopoietic progenitors in vitro. This pilot study provides the proof-of-principle for the clinical application of biodegradable IM-loaded PMC as feasible, safe and effective ex vivo purging agents to target CML stem cells, in order to improve transplant outcome of resistant/relapsed patients or reduce IM dose escalation.

  4. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Gedde-Dahl, Tobias; Markevärn, Berit

    2011-01-01

    Biologic and clinical observations suggest that combining imatinib with IFN-a may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission......%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-a2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-a2b arm (82%) compared...... with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-a2b treatment ( 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-a2b to imatinib markedly increased the MMR rate at 12 months...

  5. Interferon alpha 2 maintenance therapy may enable high rates of treatment discontinuation in chronic myeloid leukemia.

    Science.gov (United States)

    Burchert, A; Saussele, S; Eigendorff, E; Müller, M C; Sohlbach, K; Inselmann, S; Schütz, C; Metzelder, S K; Ziermann, J; Kostrewa, P; Hoffmann, J; Hehlmann, R; Neubauer, A; Hochhaus, A

    2015-06-01

    A minority of chronic myeloid leukemia (CML) patients is capable of successfully discontinuing imatinib. Treatment modalities to increase this proportion are currently unknown. Here, we assessed the role of interferon alpha 2a (IFN) on therapy discontinuation in a previously reported cohort of 20 chronic phase CML patients who were treated upfront with IFN alpha plus imatinib followed by IFN monotherapy to maintain cytogenetic or molecular remission (MR) after imatinib discontinuation. After a median follow-up of 7.9 years (range, 5.2-12.2), relapse-free survival was 73% (8/11 patients) and 84% (5/6 patients) for patients who discontinued imatinib in major MR (MMR) and MR4/MR4.5, respectively. Ten patients discontinued IFN after a median of 4.5 years (range, 0.24-9.3). After a median of 2.8 years (range, 0.7-5.1), nine of them remain in ongoing treatment-free remission with MR5 (n=6) and MR4.5 (n=3). The four patients who still administer IFN are in stable MR5, MR4.5, MR4, and MMR, respectively. In conclusion, an IFN/imatinib induction treatment followed by a temporary IFN maintenance therapy may enable a high rate of treatment discontinuation in CML patients in at least MMR when stopping imatinib.

  6. Preoperative bone scans

    International Nuclear Information System (INIS)

    Charkes, N.D.; Malmud, L.S.; Caswell, T.; Goldman, L.; Hall, J.; Lauby, V.; Lightfoot, W.; Maier, W.; Rosemond, G.

    1975-01-01

    Strontium nitrate Sr-87m bone scans were made preoperatively in a group of women with suspected breast cancer, 35 of whom subsequently underwent radical mastectomy. In 3 of the 35 (9 percent), the scans were abnormal despite the absence of clinical or roentgenographic evidence of metastatic disease. All three patients had extensive axillary lymph node involvement by tumor, and went on to have additional bone metastases, from which one died. Roentgenograms failed to detect the metastases in all three. Occult bone metastases account in part for the failure of radical mastectomy to cure some patients with breast cancer. It is recommended that all candidates for radical mastectomy have a preoperative bone scan. (U.S.)

  7. WE-FG-202-11: Longitudinal Diffusion MRI for Treatment Assessment of Sarcoma Patients with Pre-Operative Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Y; Cao, M; Kamrava, M; Low, D; Sheng, K; Lamb, J; Agazaryan, N; Thomas, D; Hu, P [UCLA, Los Angeles, CA (United States)

    2016-06-15

    Purpose: Diffusion weighted MRI (DWI) is a promising imaging technique for early prediction of tumor response to radiation therapy. A recently proposed longitudinal DWI strategy using a Co-60 MRI guided RT system (MRIgRT) may bring functional MRI guided adaptive radiation therapy closer to clinical utility. We report our preliminary results of using this longitudinal DWI approach performed on the MRIgRT system for predicting the response of sarcoma patient to preop RT. Methods: Three sarcoma patients who underwent fractionated IMRT were recruited in this study. For all three patients DWI images were acquired immediately following his/her treatment. For each imaging session, ten slices were acquired interleaved with the b values covering the gross tumor volume (GTV). The diffusion images were processed to obtain the ADC maps using standard exponential fitting for each voxel. Regions of interest were drawn in the tumor on the diffusion images based on each patient’s clinical GTV contours. Each patient subsequently underwent surgery and the tumor necrosis score was available from standard pathology. The ADC values for each patient were compared to the necrosis scores to assess the predictive value of our longitudinal DWI for tumor response. Results: Each patient underwent 3 to 5 diffusion MRI scans depending on their treatment length. Patient 1 had a relatively unchanged ADC during the course of RT and a necrosis score of 30% at surgery. For patient 2, the mean ADC values decreased from 1.56 × 10-3 to 1.12 × 10-3 mm2/s and the patient’s necrosis score was less than 10%. Patient 3 had a slight increase in the ADC values from 0.59 × 10-3 to 0.71 × 10-3 mm2/s and patient’s necrosis score was 50%. Conclusion: Based on limited data from 3 patients, our longitudinal changes in tumor ADC assessed using the MRIgRT system correlated well with pathology results.

  8. Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imaging.

    Science.gov (United States)

    Curvo-Semedo, Luís; Lambregts, Doenja M J; Maas, Monique; Thywissen, Thomas; Mehsen, Rana T; Lammering, Guido; Beets, Geerard L; Caseiro-Alves, Filipe; Beets-Tan, Regina G H

    2011-09-01

    To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of complete tumor response (CR) after combined radiation therapy with chemotherapy (CRT) in patients with locally advanced rectal cancer (LARC) by means of volumetric signal intensity measurements and apparent diffusion coefficient (ADC) measurements and to compare the performance of DW imaging with that of T2-weighted MR volumetry. A retrospective analysis of 50 patients with LARC, for whom clinical and imaging data were retrieved from a previous imaging study approved by the local institutional ethical committee and for which all patients provided informed consent, was conducted. Patients underwent pre- and post-CRT standard T2-weighted MR and DW MR. Two independent readers placed free-hand regions of interest (ROIs) in each tumor-containing section on both data sets to determine pre- and post-CRT tumor volumes and tumor volume reduction rates (volume). ROIs were copied to an ADC map to calculate tumor ADCs. Histopathologic findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DW MR volumetry and ADC. The intraclass correlation coefficient (ICC) was used to evaluate interobserver variability and the correlation between T2-weighted and DW MR volumetry. Areas under the ROC curve (AUCs) for identification of a CR that was based on pre-CRT volume, post-CRT volume, and volume, respectively, were 0.57, 0.70, and 0.84 for T2-weighted MR versus 0.63, 0.93, and 0.92 for DW MR volumetry (P = .15, .02, .42). Pre- and post-CRT ADC and ADC AUCs were 0.55, 0.54, and 0.51, respectively. Interobserver agreement was excellent for all pre-CRT measurements (ICC, 0.91-0.96) versus good (ICC, 0.61-0.79) for post-CRT measurements. ICC between T2-weighted and DW MR volumetry was excellent (0.97) for pre-CRT measurements versus fair (0.25) for post-CRT measurements. Post-CRT DW MR

  9. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  10. Preliminary results of pre-operative 5-FU, low dose leucovorin (LV), and concurrent radiation therapy (RT) for resectable T3 rectal cancer

    International Nuclear Information System (INIS)

    Grann, Alison; Minsky, Bruce D.; Cohen, Alfred M.; Saltz, Leonard; Kelsen, David P.; Kemeny, Nancy; Ilson, David; Guillem, Jose G.; Paty, Philip B.; Bass, Joanne

    1996-01-01

    foci of tumor in the bowel wall (clinical complete response) Therefore, the total complete response rate (clinical + pathologic) was 22% ((7(32))). Operative procedures included LAR: 16, LAR/Coloanal anastomosis: 8, APR: 8. All margins were negative. Of the 25 pts thought to initially require an APR, 17 (68%) were able to undergo sphincter preserving surgery. Of the 25 pts, 5 had involvement of the anal sphincter at initial presentation and pre-op therapy was not performed with the goal of sphincter preservation since an APR was planned regardless of the degree of downstaging. Excluding those 5 pts, the incidence of sphincter preservation would have been (17(20)) (85%). The crude incidence of failure as a component of failure was local: 0%, abdominal: 10% and distant: 3%. The 2 yr actuarial disease free survival was 86% and the overall survival was 100%. CONCLUSION: Our preliminary data reveal encouraging downstaging, acute toxicity, local control, and survival rates. Additional experience is needed in order to assess the long term results. The concurrent low dose LV regimen remains our standard pre-op combined modality approach for pts with clinically resectable T3 rectal cancer

  11. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

    NARCIS (Netherlands)

    D.A. Reardon; G. Dresemann; S. Taillibert; M. Campone (Mario); M.J. van den Bent (Martin); P.M.J. Clement (Paul); E. Blomquist; L. Gordower; H. Schultz; J. Raizer; P. Hau (Peter); J. Easaw; M. Gil (Miguel); J. Tonn; A. Gijtenbeek; U. Schlegel; P. Bergström (Per); S. Green; A.E. Weir (Angela); Z. Nikolova

    2009-01-01

    textabstractBackground: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21

  12. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.

    NARCIS (Netherlands)

    Reardon, D.A.; Dresemann, G.; Taillibert, S.; Campone, M.; Bent, M. van den; Clement, P.; Blomquist, E.; Gordower, L.; Schultz, H.; Raizer, J.; Hau, P.; Easaw, J.; Gil, M.; Tonn, J.; Gijtenbeek, A.; Schlegel, U.; Bergstrom, P.; Green, S.; Weir, A.; Nikolova, Z.

    2009-01-01

    BACKGROUND: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). METHODS: A total of 231 patients with GBM at first recurrence from 21 institutions in 10

  13. An expeditious synthesis of imatinib and analogues utilising flow chemistry methods.

    Science.gov (United States)

    Hopkin, Mark D; Baxendale, Ian R; Ley, Steven V

    2013-03-21

    A flow-based route to imatinib, the API of Gleevec, was developed and the general procedure then used to generate a number of analogues which were screened for biological activity against Abl1. The flow synthesis required minimal manual intervention and was achieved despite the poor solubility of many of the reaction components.

  14. Myeloid neoplasm with prominent eosinophilia and PDGFRA rearrangement treated with imatinib mesylate

    DEFF Research Database (Denmark)

    Rathe, Mathias; Kielsgaard Kristensen, Thomas; Møller, Michael Boe

    2010-01-01

    of FIP1L1-PDGFRA positive disease has been reported. We report a 2-year-old female with a myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRA. Treatment with imatinib resulted in complete and durable clinical, hematological, and molecular remission within 3 months after starting...

  15. Chronic Myeloid Leukemia with Variant Chromosomal Translocations: Results of Treatment with Imatinib Mesylate

    Directory of Open Access Journals (Sweden)

    Rohan Bhise

    2013-01-01

    Full Text Available Objective: To evaluate the efficacy of imatinib in chronic myeloid leukemia patients with variant translocations. Methods: Forty eight chronic myeloid leukemia patients carrying variant translocations and treated with imatinib at our institute were considered for the study. Survival and response rates were evaluated. Results: The median follow up was 48 months(m. Forty three (89.58% patients achieved complete hematologic response. Thirty one (64.58% patients achieved complete cytogenetic response and 19(39.58% achieved major molecular response anytime during their follow up period. Only 18.75% of the patients achieved complete cytogenetic response and major molecular response within the stipulated time frames.The estimated overall survival at 48 m median follow up was 81.2%.The progression free survival was also 81.2% and the event free survival was 79.1%.There was no significant survival difference between low vs intermediate and high risk sokal group. Conclusion: We report suboptimal responses to imatinib in chronic myeloid leukemia with variant translocations. Further studies with imatinib and the newer more active drugs dasatinib and nilotinib are justified.

  16. The role of anxiolytic premedication in reducing preoperative anxiety.

    LENUS (Irish Health Repository)

    Carroll, Jennifer K

    2012-01-01

    Prevention of preoperative anxiety with anxiolytic premedication is associated with improved preoperative outcomes in surgical patients. The objective of the authors\\' study was to evaluate the percentage of surgical patients that are prescribed premedication for preoperative anxiety before their anticipated surgical procedure. A prospective study was carried out by theatre nursing staff in the theatre reception bay of a university teaching hospital. A questionnaire was designed to record the number of patients that described symptoms consistent with preoperative anxiety. The number of patients that had been offered anxiolytic premedication for preoperative anxiety was also recorded. Consent was obtained from 115 consecutive surgical patients (male, n=52; female, n=63). Of these, 66% (n=76) reported anxiety before their surgical procedure (male: n=27, female: n=49). Premedication with a low-dose benzodiazepine was prescribed by an anaesthetist in 4% of cases (n=5). Patients that received premedication preoperatively reported effective relief of their anxiety symptoms This study demonstrates that preoperative patient anxiety is highly prevalent. The authors\\' findings suggest that premedication with anxiolytic pharmacological therapy may be an underused therapeutic resource for managing preoperative patient anxiety.

  17. [Modern therapy of chronic myeloid leukemia: an example for paradigma shift in hemato-oncology].

    Science.gov (United States)

    Leitner, A A; Hehlmann, R

    2011-02-01

    Chronic myeloid leukemia (CML) is exceptional amongst neoplasias since its underlying pathomechanism has been elucidated, and potent well tolerated targeted drugs, the tyrosine kinase inhibitors (TKI), are available for treatment. They convincingly improve prognosis while retaining good quality of life. Aims of therapy are complete remissions as well as prolongation of life and cure. Imatinib 400 mg per day is current standard therapy. There are hints for a better outcome with a higher initial imatinib dose or with combination therapy. Even after achievement of complete molecular response continuous therapy might be necessary in most cases. In case of imatinib intolerance or failure, the second generation TKI dasatinib and nilotinib and allogeneic stem cell transplantation are available. The use of second generation TKI as first line treatment might further improve prognosis. The therapeutic response should be regularly monitored according to international recommendations.

  18. Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib

    Science.gov (United States)

    Hochhaus, Andreas; le Coutre, Philipp D.; Rosti, Gianantonio; Pinilla-Ibarz, Javier; Jabbour, Elias; Gillis, Kathryn; Woodman, Richard C.; Blakesley, Rick E.; Giles, Francis J.; Kantarjian, Hagop M.; Baccarani, Michele

    2011-01-01

    Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497 PMID:21467546

  19. Management of CML in the Pediatric Age Group: Imatinib Mesylate or SCT.

    Science.gov (United States)

    El-Alfy, Mohsen S; Al-Haddad, Alaa M; Hamed, Ahmed A

    2010-12-01

    Management of CML has changed markedly since the introduction of tyrosine kinase inhibitors (TKIs). However stem cell transplantation (SCT) remains a valid therapeutic modality especially in developing countries due to its relatively lower cost. We aim to compare between imatinib mesylate and SCT as regard outcome in CML in the pediatric age group. Forty-eight patients with newly diagnosed CML in the chronic phase, aged 3 to 18 years were enrolled in this prospective study. Patients without a matched donor (Group I; N=30) were assigned to receive imatinib mesylate at a dose of 340mg÷m2÷day, while patients with a fully matched related donor (Group II; N=18), were offered SCT. Response (hematologic, cytogenetic and molecular), side effects and survival were analyzed. Complete hematologic response was obtained in 97% of the patients in group I and 94% in group II. Major cytogenetic response (CyR) was obtained in 80% of patients in group I and 100% in group II. Complete CyR was 57% in group I and 64% in group II. Major molecular response (MMR) was 36% in group I and 50% in group II with no significant difference between both groups. Six years overall survival (OS) was 87% in the 1st group and 61% in the 2nd group (pSCT group (55% had GVHD and 78% had infection). Imatinib mesylate has a superior OS and EFS than SCT in children. It is generally safe and well tolerated. Imatinib mesylate should be the 1st line treatment of pediatric patients with CML in the chronic phase. CML- Imatinib- SCT- Pediatrics.

  20. Preoperative modifiable risk factors in colorectal surgery

    DEFF Research Database (Denmark)

    van Rooijen, Stefanus; Carli, Francesco; Dalton, Susanne O

    2017-01-01

    in higher mortality rates and greater hospital costs. The number and severity of complications is closely related to patients' preoperative performance status. The aim of this study was to identify the most important preoperative modifiable risk factors that could be part of a multimodal prehabilitation...... program. METHODS: Prospectively collected data of a consecutive series of Dutch CRC patients undergoing colorectal surgery were analyzed. Modifiable risk factors were correlated to the Comprehensive Complication Index (CCI) and compared within two groups: none or mild complications (CCI ... complications (CCI ≥20). Multivariate logistic regression analysis was done to explore the combined effect of individual risk factors. RESULTS: In this 139 patient cohort, smoking, malnutrition, alcohol consumption, neoadjuvant therapy, higher age, and male sex, were seen more frequently in the severe...

  1. WT1 expression in peripheral leukocytes of patients with chronic myeloid leukemia serves for the prediction of Imatinib resistance

    Czech Academy of Sciences Publication Activity Database

    Otahalová, E.; Ullmannová-Benson, Veronika; Klamová, H.; Haškovec, C.

    2009-01-01

    Roč. 56, č. 5 (2009), s. 393-397 ISSN 0028-2685 Institutional research plan: CEZ:AV0Z50200510 Keywords : Imatinib * drug resistance * cml Subject RIV: EC - Immunology Impact factor: 1.192, year: 2009

  2. Bosutinib, dasatinib, imatinib, nilotinib, and ponatinib differentially affect the vascular molecular pathways and functionality of human endothelial cells.

    Science.gov (United States)

    Gover-Proaktor, Ayala; Granot, Galit; Pasmanik-Chor, Metsada; Pasvolsky, Oren; Shapira, Saar; Raz, Oshrat; Raanani, Pia; Leader, Avi

    2018-05-09

    The tyrosine kinase inhibitors (TKIs), nilotinib, ponatinib, and dasatinib (but not bosutinib or imatinib), are associated with vascular adverse events (VAEs) in chronic myeloid leukemia (CML). Though the mechanism is inadequately understood, an effect on vascular cells has been suggested. We investigated the effect of imatinib, nilotinib, dasatinib, bosutinib, and ponatinib on tube formation, cell viability, and gene expression of human vascular endothelial cells (HUVECs). We found a distinct genetic profile in HUVECs treated with dasatinib, ponatinib, and nilotinib compared to bosutinib and imatinib, who resembled untreated samples. However, unique gene expression and molecular pathway alterations were detected between dasatinib, ponatinib, and nilotinib. Angiogenesis/blood vessel-related pathways and HUVEC function (tube formation/viability) were adversely affected by dasatinib, ponatinib, and nilotinib but not by imatinib or bosutinib. These results correspond to the differences in VAE profiles of these TKIs, support a direct effect on vascular cells, and provide direction for future research.

  3. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial.

    Science.gov (United States)

    Lipton, Jeffrey H; Chuah, Charles; Guerci-Bresler, Agnès; Rosti, Gianantonio; Simpson, David; Assouline, Sarit; Etienne, Gabriel; Nicolini, Franck E; le Coutre, Philipp; Clark, Richard E; Stenke, Leif; Andorsky, David; Oehler, Vivian; Lustgarten, Stephanie; Rivera, Victor M; Clackson, Timothy; Haluska, Frank G; Baccarani, Michele; Cortes, Jorge E; Guilhot, François; Hochhaus, Andreas; Hughes, Timothy; Kantarjian, Hagop M; Shah, Neil P; Talpaz, Moshe; Deininger, Michael W

    2016-05-01

    Ponatinib has shown potent activity against chronic myeloid leukaemia that is resistant to available treatment, although it is associated with arterial occlusion. We investigated whether this activity and safety profile would result in superior outcomes compared with imatinib in previously untreated patients with chronic myeloid leukaemia. The Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia (EPIC) study was a randomised, open-label, phase 3 trial designed to assess the efficacy and safety of ponatinib, compared with imatinib, in newly diagnosed patients with chronic-phase chronic myeloid leukaemia. Patients from 106 centres in 21 countries were randomly assigned (1:1, with stratification by Sokal score at diagnosis) using an interactive voice and web response system to receive oral ponatinib (45 mg) or imatinib (400 mg) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met. Eligible patients were at least 18 years of age, within 6 months of diagnosis, and Philadelphia chromosome-positive by cytogenetic assessment, with Eastern Cooperative Oncology Group performance status of 0-2, and had not previously been treated with tyrosine kinase inhibitors. The primary endpoint was major molecular response at 12 months. Patients who remained on study and had molecular assessments at specified timepoints were studied at those timepoints. Safety analyses included all treated patients, as per study protocol. This trial is registered with ClinicalTrials.gov, number NCT01650805. Between Aug 14, 2012, and Oct 9, 2013, 307 patients were randomly assigned to receive ponatinib (n=155) or imatinib (n=152). The trial was terminated early, on Oct 17, 2013, following concerns about vascular adverse events observed in patients given ponatinib in other trials. Trial termination limited assessment of the primary endpoint of major molecular response at 12 months, as only 13 patients in the imatinib group and ten patients in the

  4. Preoperative radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Sarashina, Hiromi; Saito, Norio; Nunomura, Masao; Takiguchi, Nobuhiro; Koda, Keishi; Sano, Takahisa; Nakashima, Nobuyuki

    1992-01-01

    Eighty patients with rectal cancer received a total of 30.6 Gy to the whole pelvic cavity and then a 12 Gy boost (4 fractions) especially to the pelvis minor including tumor. Tumor reduction, as found on X-ray film, endoscopy, endoscopic ultrasonography, CT and MRI, was proportional to histological outcome. Pathological effectiveness was reversely associated with tubular infiltration and extramural invasion. Definite cancer invasion into the adventitia, 2 mm or less from the surgical margin, and lymph node metastasis to group II were significantly responsive to irradiation. In these cases, local failure was also controlled by irradiation. The loco-regional occurrence rate was 6.0% in the irradiated group and 28.0% in the non-irradiated group; and the 5-year survival rate was 69.2% in the irradiated group and 56.0% in the non-irradiated group. It was also significantly higher in patients histopathologically judged as effective than the other patients. (N.K.)

  5. Adopting preoperative fasting guidelines.

    Science.gov (United States)

    Anderson, Megan; Comrie, Rhonda

    2009-07-01

    In 1999, the American Society of Anesthesiologists adopted preoperative fasting guidelines to enhance the quality and efficiency of patient care. Guidelines suggest that healthy, non-pregnant patients should fast six hours from solids and two hours from liquids. Although these guidelines are in place, studies suggest that providers are still using the blanket statement "NPO after midnight" without regard to patient characteristics, the procedure, or the time of the procedure. Using theory to help change provider's beliefs may help make change more successful. Rogers' Theory of Diffusion of Innovations can assist in changing long-time practice by laying the groundwork for an analysis of the benefits and disadvantages of proposed changes, such as changes to fasting orders, while helping initiate local protocols instead of additional national guidelines.

  6. Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein.

    LENUS (Irish Health Repository)

    Elzinga, Baukje M

    2013-06-01

    Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr-Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr-Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr-Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr-Abl is sequestered into vesicular structures that co-localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1\\/ATG7). Pharmacological inhibition of autophagy also reduced Bcr-Abl\\/LC3 co-localization in both K562 and CML patient cells. Bcr-Abl protein expression was reduced with imatinib treatment. Inhibition of both autophagy and proteasome activity in imatinib treated cells was required to restore Bcr-Abl protein levels to those of untreated cells. This ability to down-regulate Bcr-Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of imatinib.

  7. A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT and intraoperative radiation therapy (IORT in patients with retroperitoneal soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Roeder Falk

    2012-07-01

    Full Text Available Abstract Background Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT are considered. Methods/design The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy followed by surgery and IORT (10–12 Gy in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. Discussion The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. Trial registration NCT01566123

  8. A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma

    International Nuclear Information System (INIS)

    Roeder, Falk; Hensley, Frank W; Buechler, Markus W; Debus, Juergen; Koch, Moritz; Weitz, Juergen; Bischof, Marc; Schulz-Ertner, Daniela; Nikoghosyan, Anna V; Huber, Peter E; Edler, Lutz; Habl, Gregor; Krempien, Robert; Oertel, Susanne; Saleh-Ebrahimi, Ladan

    2012-01-01

    Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT) are considered. The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy) followed by surgery and IORT (10–12 Gy) in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. NCT01566123

  9. The chimeric ubiquitin ligase SH2-U-box inhibits the growth of imatinib-sensitive and resistant CML by targeting the native and T315I-mutant BCR-ABL.

    Science.gov (United States)

    Ru, Yi; Wang, Qinhao; Liu, Xiping; Zhang, Mei; Zhong, Daixing; Ye, Mingxiang; Li, Yuanchun; Han, Hua; Yao, Libo; Li, Xia

    2016-06-22

    Chronic myeloid leukemia (CML) is characterized by constitutively active fusion protein tyrosine kinase BCR-ABL. Although the tyrosine kinase inhibitor (TKI) against BCR-ABL, imatinib, is the first-line therapy for CML, acquired resistance almost inevitably emerges. The underlying mechanism are point mutations within the BCR-ABL gene, among which T315I is notorious because it resists to almost all currently available inhibitors. Here we took use of a previously generated chimeric ubiquitin ligase, SH2-U-box, in which SH2 from the adaptor protein Grb2 acts as a binding domain for activated BCR-ABL, while U-box from CHIP functions as an E3 ubiquitin ligase domain, so as to target the ubiquitination and degradation of both native and T315I-mutant BCR-ABL. As such, SH2-U-box significantly inhibited proliferation and induced apoptosis in CML cells harboring either the wild-type or T315I-mutant BCR-ABL (K562 or K562R), with BCR-ABL-dependent signaling pathways being repressed. Moreover, SH2-U-box worked in concert with imatinib in K562 cells. Importantly, SH2-U-box-carrying lentivirus could markedly suppress the growth of K562-xenografts in nude mice or K562R-xenografts in SCID mice, as well as that of primary CML cells. Collectively, by degrading the native and T315I-mutant BCR-ABL, the chimeric ubiquitin ligase SH2-U-box may serve as a potential therapy for both imatinib-sensitive and resistant CML.

  10. Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

    Science.gov (United States)

    Desjardins, Annick; Quinn, Jennifer A; Vredenburgh, James J; Sathornsumetee, Sith; Friedman, Allan H; Herndon, James E; McLendon, Roger E; Provenzale, James M; Rich, Jeremy N; Sampson, John H; Gururangan, Sridharan; Dowell, Jeannette M; Salvado, August; Friedman, Henry S; Reardon, David A

    2007-05-01

    Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

  11. Results of plasma N-terminal pro B-type natriuretic peptide and cardiac troponin monitoring in GIST patients do not support the existence of imatinib-induced cardiotoxicity

    NARCIS (Netherlands)

    Perik, P. J.; Rikhof, B.; de Jong, F. A.; Verweij, J.; Gietema, J. A.; van der Graaf, W. T. A.

    Background: Recently, case reports of patients treated with imatinib (imatinib mesylate; Gleevec (R); Glvec (R)) indicated that this tyrosine kinase inhibitor may induce cardiomyopathy. Consequently, careful cardiac monitoring was advocated for clinical studies. The purpose of this study was to

  12. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.

    Science.gov (United States)

    Reardon, D A; Dresemann, G; Taillibert, S; Campone, M; van den Bent, M; Clement, P; Blomquist, E; Gordower, L; Schultz, H; Raizer, J; Hau, P; Easaw, J; Gil, M; Tonn, J; Gijtenbeek, A; Schlegel, U; Bergstrom, P; Green, S; Weir, A; Nikolova, Z

    2009-12-15

    We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

  13. Imatinib preserves blood-brain barrier integrity following experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Zhan, Yan; Krafft, Paul R; Lekic, Tim; Ma, Qingyi; Souvenir, Rhonda; Zhang, John H; Tang, Jiping

    2015-01-01

    Blood-brain barrier (BBB) disruption and consequent edema formation contribute to the development of early brain injury following subarachnoid hemorrhage (SAH). Various cerebrovascular insults result in increased platelet-derived growth factor receptor (PDGFR)-α stimulation, which has been linked to BBB breakdown and edema formation. This study examines whether imatinib, a PDGFR inhibitor, can preserve BBB integrity in a rat endovascular perforation SAH model. Imatinib (40 or 120 mg/kg) or a vehicle was administered intraperitoneally at 1 hr after SAH induction. BBB leakage, brain edema, and neurological deficits were evaluated. Total and phosphorylated protein expressions of PDGFR-α, c-Src, c-Jun N-terminal kinase (JNK), and c-Jun were measured, and enzymatic activities of matrix metalloproteinase (MMP)-2 and MMP-9 were determined in the injured brain. Imatinib treatment significantly ameliorated BBB leakage and edema formation 24 hr after SAH, which was paralleled by improved neurological functions. Decreased brain expressions of phosphorylated PDGFR-α, c-Src, JNK, and c-Jun as well as reduced MMP-9 activities were found in treated animals. PDGFR-α inhibition preserved BBB integrity following experimental SAH; however, the protective mechanisms remain to be elucidated. Targeting PDGFR-α signaling might be advantageous to ameliorate early brain injury following SAH. © 2014 Wiley Periodicals, Inc.

  14. Considering the role of radiation therapy for gastrointestinal stromal tumor

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    Corbin KS

    2014-05-01

    Full Text Available Kimberly S Corbin,1 Hedy L Kindler,2 Stanley L Liauw31Department of Radiation Oncology, Memorial Medical Center, Springfield, IL, USA; 2Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA; 3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USAAbstract: Gastrointestinal stromal tumors (GISTs are rare mesenchymal tumors arising in the gastrointestinal tract. Over the last decade, the management and prognosis of GISTs has changed dramatically with molecular characterization of the c-kit mutation and the adoption of targeted systemic therapy. Currently, the standard of care for resectable tumors is surgery, followed by adjuvant imatinib for tumors at high risk for recurrence. Inoperable or metastatic tumors are treated primarily with imatinib. Despite excellent initial response rates, resistance to targeted therapy has emerged as a common clinical problem, with relatively few therapeutic solutions. While the treatment of GISTs does not commonly include radiotherapy, radiation therapy could be a valuable contributing modality. Several case reports indicate that radiation can control locally progressive, drug-resistant disease. Further study is necessary to define whether radiation could potentially prevent or delay the onset of drug resistance, or improve outcomes when given in combination with imatinib.Keywords: GIST, imatinib, radiotherapy

  15. Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

    Science.gov (United States)

    Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

    2015-01-01

    Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent

  16. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

    Directory of Open Access Journals (Sweden)

    Ali Kadivar

    Full Text Available Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT. Conventional imatinib mesylate (Gleevec tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M, with Sodium alginate (SA and Carbomer 934P (CP as release-retarding polymers, sodium bicarbonate (NaHCO3 as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec in 0.1 N HCl (pH 1.2 at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec. Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours

  17. Increased financial burden among patients with chronic myelogenous leukaemia receiving imatinib in Japan: a retrospective survey

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    Kodama Yuko

    2012-04-01

    Full Text Available Abstract Background The financial burden of medical expenses has been increasing for cancer patients. We investigated the relationship between household income and financial burden among patients with chronic myelogenous leukaemia (CML who have been treated with imatinib. Methods A questionnaire was distributed to 1200 patients between May and August 2009. We retrospectively surveyed their household incomes, out-of-pocket medical expenses, final co-payments after refunds, and the perceived financial burden of their medical expenses in 2000, 2005 and 2008. Results A total of 577 patients completed the questionnaire. Their median age was 61 years (range, 15–94. A financial burden was felt by 41.2 % (28 of 68 of the patients treated with imatinib in 2000, 70.8 % (201 of 284 in 2005, and 75.8 % (400 of 528 in 2008. Overall, 182 patients (31.7 % considered its discontinuation because of the financial burden and 15 (2.6 % temporarily stopped their imatinib prescription. In 2000, 2005 and 2008, the patients’ median annual household incomes were 49,615 US Dollars (USD, 38,510 USD and 36,731 USD, respectively, with an average currency exchange rate of 104 Yen/USD in 2008. Their median annual out-of-pocket expenses were 11,548, 12,067 and 11,538 USD and their median final annual co-payments were 4,375, 4,327 and 3,558 USD, respectively. Older patients (OR = 0.96, 95 % CI: 0.95–0.98, p ≪ 0.0001 for 1-year increments, and patients with higher household incomes (OR = 0.92, 95 % CI: 0.85–0.99, p = 0.03 for 10,000 USD-increments were less likely to have considered discontinuing their imatinib treatment. Conversely, patients with higher annual final co-payments (OR = 2.21, 95 % CI: 1.28–4.28, p = 0.004 for 10,000 USD-increments were more likely to have considered discontinuing their imatinib treatment. Conclusions The proportion of CML patients who sensed a financial burden increased between 2000 and 2008

  18. Preoperative alcoholism and postoperative morbidity

    DEFF Research Database (Denmark)

    Tonnesen, H; Kehlet, H

    1999-01-01

    BACKGROUND: Preoperative risk assessment has become part of daily clinical practice, but preoperative alcohol abuse has not received much attention. METHODS: A Medline search was carried out to identify original papers published from 1967 to 1998. Relevant articles on postoperative morbidity...... in alcohol abusers were used to evaluate the evidence. RESULTS: Prospective and retrospective studies demonstrate a twofold to threefold increase in postoperative morbidity in alcohol abusers, the most frequent complications being infections, bleeding and cardiopulmonary insufficiency. Wound complications...... to postoperative morbidity. CONCLUSION: Alcohol consumption should be included in the preoperative assessment of likely postoperative outcome. Reduction of postoperative morbidity in alcohol abusers may include preoperative alcohol abstinence to improve organ function, or perioperative alcohol administration...

  19. Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study

    NARCIS (Netherlands)

    Tournade, M. F.; Com-Nougué, C.; de Kraker, J.; Ludwig, R.; Rey, A.; Burgers, J. M.; Sandstedt, B.; Godzinski, J.; Carli, M.; Potter, R.; Zucker, J. M.

    2001-01-01

    To determine the optimal duration of preoperative chemotherapy to further increase the proportion of stage I tumors by comparison of two regimens in the treatment of patients older than 6 months who have unilateral Wilms' tumor. Eligible patients (n = 382) initially received four weekly doses of

  20. Activity and side effects of imatinib in patients with gastrointestinal stromal tumors: data from a german multicenter trial

    Directory of Open Access Journals (Sweden)

    Schlemmer M

    2011-05-01

    Full Text Available Abstract Gastrointestinal stromal tumors (GIST are mesenchymal tumors that in the past were classified as leiomyosarcomas or leiomyomas not responding to standard sarcoma chemotherapy. In several phase I and II trials the efficacy and safety of imatinib was shown before the largest trial ever performed in a single sarcoma entity revealed response rates (CR/PR of 52%. This multicenter phase II trial presented here was performed to open access to imatinib for patients with unresectable or metastastatic GIST when the EORTC 62005 trial had been closed before imatinib was approved in Germany. It was designed to follow the best clinical response and to assess the efficacy, safety and tolerability of imatinib 400 mg/d in patients with unresectable or metastatic gastrointestinal stromal tumor. 95 patients were treated in this trial with Imatinib 400 mg/d. Four patients (4.6% attained a complete response and 26 patients (29.9% a partial response to imatinib treatment. Forty-one patients (47.1% revealed a stable disease and 16 patients (18.4% had a progressive disease. Of the progressive patients 22% showed a partial response and 67% showed stable disease after escalating the dose to 800 mg. According to SWOG tumor response classification, 66 patients (70% were free of progression within the first year of treatment. Seventy-one patients (74.7% experienced adverse events or severe adverse events with a suspected relationship to the study drug. Among these, the most common were nausea (n = 27 patients, 28.4%, eyelid edema and peripheral edema in 23 patients each (24.2%, diarrhea in 20 patients (21.1%, muscle cramps in 15 patients (15.8% and fatigue in 13 patients (13.7%. Imatinib 400 mg/d led to disease stabilisation in 81,6% of patients with unresectable or metastatic malignant GIST. Thirty-four percent of patients attained a tumor remission (partial or complete response. The safety profile of imatinib based on adverse event assessment is favorable

  1. Phase I Study of INNO-406, a Dual Abl/Lyn Kinase Inhibitor, in Philadelphia Chromosome-Positive Leukemias Post-Imatinib Resistance or Intolerance

    Science.gov (United States)

    Kantarjian, H.; le Coutre, P.; Cortes, J.; Pinilla-Ibarz, J.; Nagler, A.; Hochhaus, A.; Kimura, S.; Ottmann, O.

    2010-01-01

    BACKGROUND INNO-406, an oral dual Abl/Lyn tyrosine kinase inhibitor (TKI), demonstrates specific Lyn kinase activity with no or limited activity against other Src-family member kinases. Several Bcr-Abl kinase domain mutations are sensitive to INNO-406 in vitro, including the F317L and F317V mutations. In this study, we evaluated INNO-406 in Philadelphia (Ph) chromosome–positive chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) post-imatinib resistance or intolerance. METHODS A dose escalation study was conducted with a starting dose of 30mg administered orally once daily. Cohorts of at least 3 patients were treated at each dose level until the maximum tolerated dose (MTD) was reached. Twice-daily (BID) dosing was also evaluated. Therapy was allowed for a maximum of 24 months. RESULTS INNO-406 was administered to 56 patients with imatinib resistance (n=40) or intolerance (n=16). Other previous treatments included nilotinib (n=20), dasatinib (n=26), and dasatinib/nilotinib (n=9). Common mutations upon study entry included Y253H (n=6), G250E (n=4), T315I (n=4) and F317L (n=3). Among 31 patients with CML in chronic phase treated with INNO-406, the major cytogenetic response rate was 19%. In this study, no responses were seen in patients with CML-AP, CML-BP, or Ph-positive ALL. Dose-limiting toxicities (DLTs) at INNO-406 480mg BID were liver function abnormalities and thrombocytopenia. CONCLUSIONS INNO-406 showed anti-CML efficacy in this heavily pretreated study population. Based on the classical determinations of both DLT and MTD, the recommended phase 2 dose of INNO-406 is 240mg orally BID. Lower doses of INNO-406 may be equally effective and should be explored. PMID:20310049

  2. Tratamento da recidiva da leucemia mielóide crônica após transplante de medula óssea alogênico utilizando mesilato de imatinibe: relato de três casos Treatment of chronic myelogenous leukemia relapse after allogeneic bone marrow transplantation with imatinib mesylate: report of three cases

    Directory of Open Access Journals (Sweden)

    Ronald Pallotta

    2006-06-01

    Full Text Available O mesilato de imatinibe (MI, inibidor seletivo da tirosinoquinase envolvido na patogênese da leucemia mielóide crônica (LMC, tem se constituído como terapia farmacológica de primeira linha para o tratamento desta doença. A infusão de linfócitos do doador (DLI tem sido considerada como tratamento padrão para recidiva da LMC após transplante de medula óssea (TMO alogênico, apesar de estar freqüentemente associado à ocorrência de doença do enxerto contra hospedeiro e mielossupressão. Por apresentar resultados satisfatórios e boa tolerabilidade no tratamento da LMC, os autores empregaram o mesilato de imatinib como terapêutica alternativa à DLI em pacientes que sofreram recidiva após o TMO. Obtiveram sucesso em dois casos, sendo que em um houve retorno comprovado do quimerismo do doador. No terceiro caso houve progressão da doença e o paciente foi encaminhado para segundo TMO. Desta forma, devido ao caráter recente do tema, este estudo descritivo sugere que esta opção terapêutica possa ser estudada como alternativa na recaída pós-TMO.Imatinib mesylate (MI, a selective tyrosine kinase inhibitor involved in the pathogenesis of chronic myelogenous leukemia (CML, has become the first-line treatment for this disease. Donor lymphocyte infusion (DLI has been considered as the standard treatment for relapse after allogeneic bone marrow transplantation (BMT, even though it is frequently associated with graft versus host disease and myelosuppression. Because of the satisfactory results and tolerance of the treatment of CML, the authors used MI as an alternative therapy for DLI in patients that relapsed after BMT. They obtained cytogenetic remission in two cases, with, in one case, proven conversion to the donor chimera. The third case evolved with progression of the disease and a second BMT was required. Since this is a new alternative, this descriptive study suggests it should be considered as an alternative therapy for relapse

  3. Phase I Pharmacokinetic Study of the VEGFR Tyrosine Kinase Inhibitor Vatalanib (PTK787) plus Imatinib and Hydroxyurea for Malignant Glioma

    Science.gov (United States)

    Reardon, David A.; Egorin, Merrill J.; Desjardins, Annick; Vredenburgh, James J.; Beumer, Jan H.; Lagattuta, Theodore F.; Gururangan, Sridharan; Herndon, James E.; Salvado, August J.; Friedman, Henry S.

    2009-01-01

    Background We determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor, vatalanib, when administered with imatinib and hydroxyurea on a continuous daily schedule among recurrent malignant glioma patients. Methods All patients received 500 mg of hydroxyurea twice daily. Imatinib was dosed at 400 mg per day for patients not taking enzyme-inducing antiepileptic drugs (EIAEDs; stratum A) and at 500 mg twice-a-day for patients taking EIAEDs (stratum B). Vatalanib was escalated from 500 mg to 1250 mg twice daily in successive cohorts, independently for each stratum. Pharmacokinetics of each drug were assessed. Results Thirty-seven recurrent patients, including 34 (92%) with glioblastoma and 3 (8%) with grade 3 malignant glioma, were enrolled. Nineteen patients (51%) were taking EIAEDs. The MTD of vatalanib for all patients was 1000 mg twice-a-day. DLTs were hematologic, gastrointestinal, renal and hepatic. No patients developed intracranial hemorrhage. Concurrent administration of imatinib and hydroxyurea did not affect vatalanib exposure, but EIAEDs decreased vatalanib and imatinib plasma exposures. Conclusion Vatalanib doses up to 1000 mg twice-a-day combined with imatinib and hydroxyurea are well tolerated. Strategies to target tumor blood vessel endothelial cells and pericytes by inhibiting VEGFR and PDGFR, respectively, are safe among recurrent malignant glioma patients and may enhance anti-angiogenesis activity. PMID:19248046

  4. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Gedde-Dahl, Tobias; Markevärn, Berit

    2011-01-01

    Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remissio...

  5. p53 Gene (NY-CO-13 Levels in Patients with Chronic Myeloid Leukemia: The Role of Imatinib and Nilotinib

    Directory of Open Access Journals (Sweden)

    Hayder M. Al-kuraishy

    2018-01-01

    Full Text Available The p53 gene is also known as tumor suppressor p53. The main functions of the p53 gene are an anticancer effect and cellular genomic stability via various pathways including activation of DNA repair, induction of apoptosis, and arresting of cell growth at the G1/S phase. Normally, the p53 gene is inactivated by mouse double minute 2 proteins (mdm2, but it is activated in chronic myeloid leukemia (CML. Tyrosine kinase inhibitors are effective chemotherapeutic agents in the management of CML. The purpose of the present study was to evaluate the differential effect of imatinib and nilotinib on p53 gene serum levels in patients with CML. A total number of 60 patients with chronic myeloid leukemia with ages ranging from 47 to 59 years were recruited from the Iraqi Hematology Center. They started with tyrosine kinase inhibitors as first-line chemotherapy. They were divided into two groups—Group A, 29 patients treated with imatinib and Group B, 31 patients treated with nilotinib—and compared with 28 healthy subjects for evaluation p53 serum levels regarding the selective effect of either imatinib or nilotinib. There were significantly (p < 0.01 high p53 gene serum levels in patients with CML (2.135 ± 1.44 ng/mL compared to the control (0.142 ± 0.11 ng/mL. Patients with CML that were treated with either imatinib or nilotinib showed insignificant differences in most of the hematological profile (p > 0.05 whereas, p53 serum levels were high (3.22 ± 1.99 ng/mL in nilotinib-treated patients and relatively low (1.18 ± 0.19 ng/mL in imatinib-treated patients (p = 0.0001. Conclusions: Nilotinib is more effective than imatinib in raising p53 serum levels in patients with chronic myeloid leukemia.

  6. Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

    Science.gov (United States)

    Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E

    2009-10-01

    Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

  7. A decrease in ubiquitination and resulting prolonged life-span of KIT underlies the KIT overexpression-mediated imatinib resistance of KIT mutation-driven canine mast cell tumor cells.

    Science.gov (United States)

    Kobayashi, Masato; Kuroki, Shiori; Kurita, Sena; Miyamoto, Ryo; Tani, Hiroyuki; Tamura, Kyoichi; Bonkobara, Makoto

    2017-10-01

    Overexpression of KIT is one of the mechanisms that contributes to imatinib resistance in KIT mutation-driven tumors. Here, the mechanism underlying this overexpression of KIT was investigated using an imatinib-sensitive canine mast cell tumor (MCT) line CoMS, which has an activating mutation in KIT exon 11. A KIT-overexpressing imatinib-resistant subline, rCoMS1, was generated from CoMS cells by their continuous exposure to increasing concentrations of imatinib. Neither a secondary mutation nor upregulated transcription of KIT was detected in rCoMS1 cells. A decrease in KIT ubiquitination, a prolonged KIT life-span, and KIT overexpression were found in rCoMS1 cells. These events were suppressed by withdrawal of imatinib and were re-induced by re‑treatment with imatinib. These findings suggest that imatinib elicited overexpression of KIT via suppression of its ubiquitination. These results also indicated that imatinib-induced overexpression of KIT in rCoMS1 cells was not a permanently acquired feature but was a reversible response of the cells. Moreover, the pan deubiquitinating enzyme inhibitor PR619 prevented imatinib induction of KIT overexpression, suggesting that the imatinib-induced decrease in KIT ubiquitination could be mediated by upregulation and/or activation of deubiquitinating enzyme(s). It may be possible that a similar mechanism of KIT overexpression underlies the acquisition of imatinib resistance in some human tumors that are driven by KIT mutation.

  8. Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis

    OpenAIRE

    Shaker, Mohamed E.; Zalata, Khaled R.; Mehal, Wajahat Z.; Shiha, Gamal E.; Ibrahim, Tarek M.

    2011-01-01

    Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. Male Wistar rats received intraperitoneal injections of CCl4 twice weekly for 8 weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20 mg/kg), nilotinib (10 and 20 mg/kg) and silymarin (100 mg/kg) durin...

  9. Determination of trace level of palladium and platinum content in anticancer drug Imatinib base by ICP-MS

    International Nuclear Information System (INIS)

    Yadav, Ravi; Salunke-Gawali, Sunita

    2013-01-01

    Metal impurities in Pharmaceutical drug substance is of great concern not only because of the intrinsic toxicity of certain contaminants but also due to the opposite effect that the contaminants which may have on drug stability and shelf life. Therefore it is necessary to monitor the organic as well as inorganic impurities throughout the process of manufacturing process at every stage from raw material, intermediate and finished products. An Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) method has been developed for Palladium and Platinum content in the anticancer drug, Imatinib mesylate. Rhodium (Rh) was used as internal standard for determination of Palladium and Platinum content on in Imatinib mesylate. (author)

  10. Interventions for preoperative smoking cessation

    DEFF Research Database (Denmark)

    Thomsen, Thordis; Villebro, Nete; Møller, Ann Merete

    2014-01-01

    BACKGROUND: Smokers have a substantially increased risk of postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence, and surgery may constitute a unique opportunity for smoking cessation interventions. OBJECTIVES: The objectives of this review...... are to assess the effect of preoperative smoking intervention on smoking cessation at the time of surgery and 12 months postoperatively, and on the incidence of postoperative complications. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register in January 2014. SELECTION CRITERIA......: Randomized controlled trials that recruited people who smoked prior to surgery, offered a smoking cessation intervention, and measured preoperative and long-term abstinence from smoking or the incidence of postoperative complications or both outcomes. DATA COLLECTION AND ANALYSIS: The review authors...

  11. Imatinib and Nilotinib Off-Target Effects on Human NK Cells, Monocytes, and M2 Macrophages.

    Science.gov (United States)

    Bellora, Francesca; Dondero, Alessandra; Corrias, Maria Valeria; Casu, Beatrice; Regis, Stefano; Caliendo, Fabio; Moretta, Alessandro; Cazzola, Mario; Elena, Chiara; Vinti, Luciana; Locatelli, Franco; Bottino, Cristina; Castriconi, Roberta

    2017-08-15

    Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells. In NB, neither drug reduced the expression of ligands for activating NK receptors or upregulated that of HLA class I, B7-H3, PD-L1, and PD-L2, molecules that might limit NK cell function. Interestingly, TKIs modulated the chemokine receptor repertoire of immune cells. Acting at the transcriptional level, they increased the surface expression of CXCR4, an effect observed also in NK cells and monocytes of patients receiving imatinib for chronic myeloid leukemia. Moreover, TKIs reduced the expression of CXCR3 (in NK cells) and CCR1 (in monocytes). Monocytes also decreased the expression of M-CSFR, and low numbers of cells underwent differentiation toward macrophages. M0 and M2 macrophages were highly resistant to TKIs and maintained their phenotypic and functional characteristics. Importantly, also in the presence of TKIs, the M2 immunosuppressive polarization was reverted by TLR engagement, and M1-oriented macrophages fully activated autologous NK cells. Our results contribute to better interpreting the off-target efficacy of TKIs in tumors and to envisaging strategies aimed at facilitating antitumor immune responses. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event

    Directory of Open Access Journals (Sweden)

    Yan ZhongShu

    2011-11-01

    Full Text Available Abstract Background Imatinib mesylate has been the standard therapeutic treatment for chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor (GIST. It is well tolerated with mild adverse effects. Gynecomastia development during the course of treatment has been rarely reported. Methods Ninety-eight patients with advanced or recurrent GIST were treated with imatinib mesylate. Among the fifty-seven male patients six developed gynecomastia during the treatment. The lesions were confirmed by sonography. Sex hormone levels were determined in six patients with and without the presence of gynecomastia respectively. The patients with gynecomatia were treated with tamoxifene and the sex hormones were assayed before and after tamoxifene treatment. Results In patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5 centimeters in diameter. Their serum free testosterone levels ranged between 356.61 and 574.60 ng/dl with a mean ± SD of 408.64 ± 82.06 ng/dl (95% CI 343.03~474.25 ng/dl, which is within the normal range. The level of serum estradiol was 42.89 ± 16.54 pg/ml (95% CI 29.66~56.12 pg/ml. Three patients had higher levels (43.79~71.21 pg/ml and the others' were within normal range of 27.00~34.91 pg/ml. Six patients without the development of gynecomastia had normal free testosterone. One patient died because of large tumor burden. The sex hormones had no significant changes before and after tamoxifene treatment.(P > 0.05 Conclusions Testosterone levels were not decreased in the six GIST patients with gynecomastia. Three patients had increased serum estradiol level which suggests that imbalance of sex hormones may be the cause of gynecomastia during treatment with imatinib mesylate.

  13. Identifying and validating a combined mRNA and microRNA signature in response to imatinib treatment in a chronic myeloid leukemia cell line.

    Directory of Open Access Journals (Sweden)

    Steven Bhutra

    Full Text Available Imatinib, a targeted tyrosine kinase inhibitor, is the gold standard for managing chronic myeloid leukemia (CML. Despite its wide application, imatinib resistance occurs in 20-30% of individuals with CML. Multiple potential biomarkers have been identified to predict imatinib response; however, the majority of them remain externally uncorroborated. In this study, we set out to systematically identify gene/microRNA (miRNA whose expression changes are related to imatinib response. Through a Gene Expression Omnibus search, we identified two genome-wide expression datasets that contain expression changes in response to imatinib treatment in a CML cell line (K562: one for mRNA and the other for miRNA. Significantly differentially expressed transcripts/miRNAs post imatinib treatment were identified from both datasets. Three additional filtering criteria were applied 1 miRbase/miRanda predictive algorithm; 2 opposite direction of imatinib effect for genes and miRNAs; and 3 literature support. These criteria narrowed our candidate gene-miRNA to a single pair: IL8 and miR-493-5p. Using PCR we confirmed the significant up-regulation and down-regulation of miR-493-5p and IL8 by imatinib treatment, respectively in K562 cells. In addition, IL8 expression was significantly down-regulated in K562 cells 24 hours after miR-493-5p mimic transfection (p = 0.002. Furthermore, we demonstrated significant cellular growth inhibition after IL8 inhibition through either gene silencing or by over-expression of miR-493-5p (p = 0.0005 and p = 0.001 respectively. The IL8 inhibition also further sensitized K562 cells to imatinib cytotoxicity (p < 0.0001. Our study combined expression changes in transcriptome and miRNA after imatinib exposure to identify a potential gene-miRNA pair that is a critical target in imatinib response. Experimental validation supports the relationships between IL8 and miR-493-5p and between this gene-miRNA pair and imatinib sensitivity in a CML cell

  14. BCR-ABL V280G Mutation, Potential Role in Imatinib Resistance: First Case Report

    OpenAIRE

    Azevedo, Ana P; Reichert, Alice; Afonso, Celina; Alberca, Maria D; Tavares, Purifica??o; Lima, Fernando

    2017-01-01

    Export Date: 28 December 2017 Correspondence Address: Azevedo, A.P.; Department of Clinical Pathology, Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Estrada do Forte do Alto do Duque, Portugal; email: Chemicals/CAS: glycine, 56-40-6, 6000-43-7, 6000-44-8; hydroxyurea, 127-07-1; imatinib, 152459-95-5, 220127-57-1; nilotinib, 641571-10-0; valine, 7004-03-7, 72-18-4 References: Radich, J.P., Shah, N.P., Mauro, M.J., Integrating current treatment options ...

  15. Preoperative chemoradiotherapy for locally advanced gastric cancer

    International Nuclear Information System (INIS)

    Pepek, Joseph M; Chino, Junzo P; Willett, Christopher G; Palta, Manisha; Blazer III, Dan G; Tyler, Douglas S; Uronis, Hope E; Czito, Brian G

    2013-01-01

    To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated

  16. Preoperative chemoradiotherapy for locally advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Pepek Joseph M

    2013-01-01

    Full Text Available Abstract Background To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT for gastric cancer. Methods Patients with gastroesophageal (GE junction (Siewert type II and III or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS, local control (LC and disease-free survival (DFS were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. Results Forty-eight patients were included. Most (73% had proximal (GE junction, cardia and fundus tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75% underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Conclusions Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

  17. OUTCOME OF FRONTLINE TREATMENT WITH “GENERIC” IMATINIB IN ADULT PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN ALGERIAN POPULATION: A MULTICENTER STUDY

    Directory of Open Access Journals (Sweden)

    Mohamed Amine BEKADJA

    2017-10-01

    Full Text Available Introduction: In a developing country like Algeria, such expensive therapy is not available. Alternative approaches are needed to help these adult. In Algeria ‘imatib’ (CIPLA-India was introduced in 2006; but no study has been published yet in the North Africa region regarding response and outcome of this copy in CML patients. The goal of this multicenter study is to characterize newly adult CML in the western region of Algeria and to assess the effectiveness and safety of imatib (IM, copy as frontline therapy for patients with CML. Patients and Methods: The study was carried out in 7 hematology centers in the western Algeria. Patients, who were diagnosed to be suffering from CML between January 1st, 2007 and  December 31st, 2014 were selected for data analysis. All patients received a copy preparation, consisting of the alpha crystal form of imatinib, (IM, copy at a oral dose of 400 mg daily and monitored for tolerance and side effects while on therapy. Results: Between January 2007 and December 2014, 355 patients with CML were treated with imatib (Copy. The median follow- up of the study was 46 months (range: 13–107 months. Complete hematological response (CHR was seen in 83% of patients within 3 months. According to the Sokal score, 72% patients with low, 78% with intermediate and 69% with high risk disease achieved a CHR in 3 months (p=0.26 and according to the EUTOS score, 81% of patients with low and 70% with high risk disease achieved a CHR in 3 months (p=0.08. The major molecular response (MMR at six months (M6, M9, M12, M18 and M24 was 21%, 38%, 35%, 51% and 67% respectively and 34% of patients achieved a complete molecular response (CMR. The projected 5-year overall survival (OS rate was 83%. Side effects of imatib (copy in this study were similar to those reported previously for the entire imatinib mesylate treatment study and only 8% of patients were intolerant to imatib (copy and treated with a second generation of BCR

  18. A novel dic (17;18 (p13.1;q11.2 with loss of TP53 and BCR/ABL rearrangement in an Imatinib resistant chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Al-achkar Walid

    2012-08-01

    Full Text Available Abstract Background The so-called Philadelphia (Ph chromosome is present in more than 90% of chronic myeloid leukemia (CML cases. It results in juxtaposition of the 5′ part of the BCR gene on chromosome 22 to the 3′ part of the ABL gene on chromosome 9. Since the majority of CML cases are currently treated with Imatinib, variant rearrangements in general have no specific prognostic significance, although the mechanisms involved in resistance to therapy have yet to be investigated. The T315I mutation within the abl-gene is the most frequent one associated with resistance to tyrosine kinase inhibitors. Results This study evaluated a Ph chromosome positive CML case resistant to imatinib mesylate. A dic(17;18, loss of TP53 gene, co-expression of b2a2 and b3a2 fusions transcript and a T315I mutation were found. Conclusions We reported here a novel case of a Ph chromosome positive CML with a secondary abnormality [dic(17;18], resulting to Glivec resistance but good response to nilotinib. The dic(17;18 might be a marker for poor prognosis in CML. Our finding indicated for an aggressive progression of the disease. The patient died under the treatment due to unknown reasons.

  19. Sequential Use of Second-Generation Tyrosine Kinase Inhibitor Treatment and Intensive Chemotherapy Induced Long-Term Complete Molecular Response in Imatinib-Resistant CML Patient Presenting as a Myeloid Blast Crisis

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    Masaaki Tsuji

    2017-01-01

    Full Text Available Myeloid blast crisis of chronic myeloid leukemia (CML-MBC is rarely seen at presentation and has a poor prognosis. There is no standard therapy for CML-MBC. It is often difficult to distinguish CML-MBC from acute myeloid leukemia expressing the Philadelphia chromosome (Ph+ AML. We present a case in which CML-MBC was seen at the initial presentation in a 75-year-old male. He was treated with conventional AML-directed chemotherapy followed by imatinib mesylate monotherapy, which failed to induce response. However, he achieved long-term complete molecular response after combination therapy involving dasatinib, a second-generation tyrosine kinase inhibitor, and conventional chemotherapy.

  20. Preoperative fasting: a clinical audit.

    Science.gov (United States)

    Roberts, Stuart

    2013-01-01

    This clinical audit examines the adherence to guidelines suggested by the Royal College of Nursing (2005); the results uphold previous studies of a preoperative starving period for patients undergoing elective surgical procedures. Patients excessively starved of food or fluids report problems relating to their health. These include hunger, distress and complaints of nausea.

  1. Preoperative and intraoperative irradiation for osteosarcoma

    International Nuclear Information System (INIS)

    Furuya, Kotaro; Amino, Katsuhisa; Kawaguchi, Noriyoshi.

    1980-01-01

    1) 8 cases of osteosarcoma were treated with preoperative massive irradiation, the over 5 years survival rate was 3/8 (37.5%). 7 out of 8 cases (87.5%) metastasized to the lung. From these result, it is considered that tumorspecific immunological effect can not be expected from irradiation. Irradiation therapy is essentially a local treatment, and therefore systemic chemotherapy is necessary to prevent metastasis. 2) Osteosarcoma was considered to be radioresistant tumor previously, however local control can be obtained by direct view irradiation without the damage of surrounding tissue. This irradiation method is indicated only for young adult in whom the primary tumor is localized. 3) In the experimental study on heterotransplanted human osteosarcoma in nude mice, combined treatment with radiation and chemotherapy (HD-MTX, ADM and EDX) was proven to be more effective as compared with radiation alone. (author)

  2. Pre-operative optimisation of lung function

    Directory of Open Access Journals (Sweden)

    Naheed Azhar

    2015-01-01

    Full Text Available The anaesthetic management of patients with pre-existing pulmonary disease is a challenging task. It is associated with increased morbidity in the form of post-operative pulmonary complications. Pre-operative optimisation of lung function helps in reducing these complications. Patients are advised to stop smoking for a period of 4–6 weeks. This reduces airway reactivity, improves mucociliary function and decreases carboxy-haemoglobin. The widely used incentive spirometry may be useful only when combined with other respiratory muscle exercises. Volume-based inspiratory devices have the best results. Pharmacotherapy of asthma and chronic obstructive pulmonary disease must be optimised before considering the patient for elective surgery. Beta 2 agonists, inhaled corticosteroids and systemic corticosteroids, are the main drugs used for this and several drugs play an adjunctive role in medical therapy. A graded approach has been suggested to manage these patients for elective surgery with an aim to achieve optimal pulmonary function.

  3. Preoperative staging of rectal cancer: the MERCURY research project.

    Science.gov (United States)

    Brown, G; Daniels, I R

    2005-01-01

    The development of a surgical technique that removes the tumour and all local draining nodes in an intact package, namely total mesorectal excision (TME) surgery, has provided the impetus for a more selective approach to the administration of preoperative therapy. One of the most important factors that governs the success of TME surgery is the relationship of tumour to the circumferential resection margin (CRM). Tumour involves the CRM in up to 20% of patients undergoing TME surgery, and results in both poor survival and local recurrence. It is therefore clear that the importance of the decision regarding the use of pre-operative therapy lies with the relationship of the tumour to the mesorectal fascia. In addition, a high-spatial-resolution MRI technique will identify tumours exhibiting other poor prognostic features, namely, extramural spread >5 mm, extramural venous invasion by tumour, nodal involvement, and peritoneal infiltration. The potential benefits of a selective approach using MRI-based selection criteria are evident. That is, over 50% of patients can be treated successfully with primary surgery alone without significant risk of local recurrence or systemic failure. Of the remainder, potentially dramatic improvements may be achieved through the use of intensive and targeted preoperative therapy aimed not only at reducing the size of the primary tumour and rendering potentially irresectable tumour resectable with tumour-free circumferential margins, but also at enabling patients at high risk of systemic failure to benefit from intensive combined modality therapy aimed at eliminating micrometastatic disease.

  4. Answer to preoperative chemie radiation in locally advanced rectum cancer

    International Nuclear Information System (INIS)

    Villegas Mendez, Silvia

    2006-01-01

    Study the pre-operative combined therapy effect in the treatment of the rectum cancer cases of the Servicio de Cirugia General 2 of the Hospital Mexico. The study covers since January of 2003 until December of 2005. It has like specific objectives to analyze the effect in the tumour stages, the sphincters preservation and the recurrence. In the conclusions, it notes that the pre-operative chemie-radiation in the rectum cancer is indicated in II and III stages, in which it has showed most advantages for the patient. It describes that the time between the end of pre-operative combined treatment and the surgery must has at least six weeks to guarantee the effect in the tumour and to reduce the treatment toxicity. It concludes besides, that the complication rate after the pre-operative combined therapy and the total meso rectum excision is approximately of 33%; however, the pelvic septic complications can reduce with an ostomy of protection. It focus that the technique of sphincters preservation has showed to be effective and secure if it does a previous selection to the patients in appropriate form. To get an suitable stages must count with trans rectum endoscopic ultrasound and a tomography of suitable quality. It concludes, also, in intervened tumours after of neo-adjuvancy they don't need free distal margins of illness higher to 2 cm. The total meso rectum excision is the updated surgical recommendation in the rectum cancer [es

  5. Background parenchymal enhancement in preoperative breast MRI.

    Science.gov (United States)

    Kohara, Satoko; Ishigaki, Satoko; Satake, Hiroko; Kawamura, Akiko; Kawai, Hisashi; Kikumori, Toyone; Naganawa, Shinji

    2015-08-01

    We aimed to assess the influence of background parenchymal enhancement (BPE) on surgical planning performed using preoperative MRI for breast cancer evaluation. Between January 2009 and December 2010, 91 newly diagnosed breast cancer patients (mean age, 55.5 years; range, 30-88 years) who underwent preoperative bilateral breast MRI followed by planned breast conservation therapy were retrospectively enrolled. MRI was performed to assess the tumor extent in addition to mammography and breast ultrasonography. BPE in the contralateral normal breast MRI at the early dynamic phase was visually classified as follows: minimal (n=49), mild (n=27), moderate (n=7), and marked (n=8). The correlations between the BPE grade and age, menopausal status, index tumor size, changes in surgical management based on MRI results, positive predictive value (PPV) of MRI, and surgical margins were assessed. Patients in the strong BPE groups were significantly younger (p=0.002) and generally premenopausal (p<0.001). Surgical treatment was not changed in 67 cases (73.6%), while extended excision and mastectomy were performed in 12 cases (13.2%), each based on additional lesions on MRI. Six of 79 (7.6%) patients who underwent breast conservation therapy had tumor-positive resection margins. In cases where surgical management was changed, the PPV for MRI-detected foci was high in the minimal (91.7%) and mild groups (66.7%), and 0% in the moderate and marked groups (p=0.002). Strong BPE causes false-positive MRI findings and may lead to overly extensive surgery, whereas MRI may be beneficial in select patients with weak BPE.

  6. Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts.

    Science.gov (United States)

    Kirschner, Gyöngyi; Balla, Bernadett; Horváth, Péter; Kövesdi, Andrea; Lakatos, Gergely; Takács, István; Nagy, Zsolt; Tóbiás, Bálint; Árvai, Kristóf; Kósa, János Pál; Lakatos, Péter

    2016-09-01

    Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.

  7. Pre-operative evaluation for thorax surgery

    International Nuclear Information System (INIS)

    Silva Luis, Saenz; Morales, Oscar Alberto

    2002-01-01

    A pre-operative analysis of the function of the breathing system is made in the patient that will be taken to thorax surgery. The paper includes risk factors, pre-operative clinical evaluation and of breathing and cardiovascular system

  8. Lack of Association of Multidrug Resistance Gene-1 Polymorphisms with Treatment Outcome in Chronic Myeloid Leukemia Patients Treated with Imatinib

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    Yaya Kassogue

    2015-10-01

    Full Text Available Background: Despite the impressive results obtained with imatinib, inadequate response or resistance are observed in certain patients. It is known that imatinib is a substrate of a multidrug resistance gene (MDR1. Thus, interindividual genetic differences linked to single nucleotide polymorphisms in MDR1 may influence the metabolism of imatinib. The present study has aimed to examine the impact of MDR1 polymorphisms on the hematologic and cytogenetic responses in 70 chronic myeloid leukemia patients who received imatinib. Methods: We used a polymerase chain reaction followed by restriction fragment length polymorphism to identify different profiles of 1236C>T, 2677G>T and 3435C>T in MDR1. Results: The distribution of the three SNPs in responders and poor responders did not show any particular trend (P>0.05. The T allele was slightly higher in responders, but not significantly regardless of the type of SNP (40.3% vs. 33.8% for 1236C>T; 25% vs. 14.7% for 2677G>T and 33.3% vs. 22% for 3435C>T. The dominant model showed a similar trend (P>0.05. Diplotypes composed by the T allele in different exons were frequent in responders. Haplotype analysis showed that 1236C-2677G-3435C was slightly higher in poor responders (60.02% compared to responders (50.42%. However, 1236T-2677T-3435T was frequent in responders (16.98% compared to poor responders (13.1%. Overall, none of the haplotypes were associated with IM response in our cohort (global haplotype association test, P=0.39. Conclusion: The identification of 1236C>T, 2677G>T and 3435C>T polymorphisms may not be advantageous to predict imatinib response for our chronic myeloid leukemia patients.

  9. PTCH1 is a reliable marker for predicting imatinib response in chronic myeloid leukemia patients in chronic phase.

    Directory of Open Access Journals (Sweden)

    Juan M Alonso-Dominguez

    Full Text Available Patched homolog 1 gene (PTCH1 expression and the ratio of PTCH1 to Smoothened (SMO expression have been proposed as prognostic markers of the response of chronic myeloid leukemia (CML patients to imatinib. We compared these measurements in a realistic cohort of 101 patients with CML in chronic phase (CP using a simplified qPCR method, and confirmed the prognostic power of each in a competing risk analysis. Gene expression levels were measured in peripheral blood samples at diagnosis. The PTCH1/SMO ratio did not improve PTCH1 prognostic power (area under the receiver operating characteristic curve 0.71 vs. 0.72. In order to reduce the number of genes to be analyzed, PTCH1 was the selected measurement. High and low PTCH1 expression groups had significantly different cumulative incidences of imatinib failure (IF, which was defined as discontinuation of imatinib due to lack of efficacy (5% vs. 25% at 4 years, P = 0.013, probabilities of achieving a major molecular response (81% vs. 53% at first year, P = 0.02, and proportions of early molecular failure (14% vs. 43%, P = 0.015. Every progression to an advanced phase (n = 3 and CML-related death (n = 2 occurred in the low PTCH1 group (P<0.001 for both comparisons. PTCH1 was an independent prognostic factor for the prediction of IF. We also validated previously published thresholds for PTCH1 expression. Therefore, we confirmed that PTCH1 expression can predict the imatinib response in CML patients in CP by applying a more rigorous statistical analysis. Thus, PTCH1 expression is a promising molecular marker for predicting the imatinib response in CML patients in CP.

  10. Preoperative staging of rectal cancer

    International Nuclear Information System (INIS)

    Schaefer, A.O.; Baumann, T.; Pache, G.; Langer, M.; Wiech, T.

    2007-01-01

    Accurate preoperative staging of rectal cancer is crucial for therapeutic decision making, as local tumor extent, nodal status, and patterns of metastatic spread are directly associated with different treatment strategies. Recently, treatment approaches have been widely standardized according to large studies and consensus guidelines. Introduced by Heald, total mesorectal excision (TME) is widely accepted as the surgical procedure of choice to remove the rectum together with its enveloping tissues and the mesorectal fascia. Neoadjuvant radiochemotherapy also plays a key role in the treatment of locally advanced stages, while the use of new drugs will lead to a further improvement in oncological outcome. Visualization of the circumferential resection margin is the hallmark of any preoperative imaging and a prerequisite for high-quality TME surgery. The aim of this article is to present an overview on current cross-sectional imaging with emphasis on magnetic resonance imaging. Future perspectives in rectal cancer imaging are addressed. (orig.)

  11. Interventions for preoperative smoking cessation

    DEFF Research Database (Denmark)

    Thomsen, Thordis; Villebro, N.; Møller, Ann Merete

    2010-01-01

    Background Smokers have a substantially increased risk of postoperative complications. Preoperative smoking intervention may be effective in decreasing this incidence, and surgery may constitute a unique opportunity for smoking cessation interventions. Objectives The objective of this review...... was to assess the effect of preoperative smoking intervention on smoking cessation at the time of surgery and 12 months postoperatively and on the incidence of postoperative complications. Search strategy The specialized register of the Cochrane Tobacco Addiction Group was searched using the free text...... and keywords (surgery) or (operation) or (anaesthesia) or (anesthesia). MEDLINE, EMBASE and CINAHL were also searched, combining tobacco- and surgery-related terms. Most recent search April 2010. Selection criteria Randomized controlled trials that recruited people who smoked prior to surgery, offered...

  12. FFTF preoperational survey. Program report

    International Nuclear Information System (INIS)

    Twitty, B.L.; Bicehouse, H.J.

    1980-12-01

    The FFTF will become operational with criticality early in 1980. This facility is composed of the test reactor, fuel examination cells, expended fuel storage systems and fuel handling systems. The reactor and storage systems are sodium-cooled with the heat load dumped to the ambient air through heat exchangers. In order to assure that the operation of the FFTF has minimal impact on the environment, a monitoring program has been established. Prior to operation of a new facility, a preoperational environmental survey is required. It is the purpose of this report to briefly describe the environmental survey program and to provide the background data obtained during the preoperational phase of the survey program. Nine stations in the program of particular importance to FFTF are discussed in detail with results of monitoring given. No unexplained trends were noted

  13. The value of preoperative planning.

    Science.gov (United States)

    Graves, Matt L

    2013-10-01

    "Better to throw your disasters into the waste paper basket than to consign your patients to the scrap heap" has been a proverb of Jeff Mast, one of the greatest fracture and deformity surgeons in the history of our specialty. Stated slightly more scientifically, one of the major values of simulation is that it allows one to make mistakes in a consequence-free environment. Preoperative planning is the focus of this article. The primary goal is not to provide you with a recipe of how to steps. Rather, the primary goal of this article is to explain why preoperative planning should be standard, to clarify what should be included, and to provide examples of what can happen when planning is ignored. At the end of this, we should all feel the need to approach fracture care more intellectually with forethought, both in our own practices and in our educational system.

  14. [Preoperative fasting guidelines: an update].

    Science.gov (United States)

    López Muñoz, A C; Busto Aguirreurreta, N; Tomás Braulio, J

    2015-03-01

    Anesthesiology societies have issued various guidelines on preoperative fasting since 1990, not only to decrease the incidence of lung aspiration and anesthetic morbidity, but also to increase patient comfort prior to anesthesia. Some of these societies have been updating their guidelines, as such that, since 2010, we now have 2 evidence-based preoperative fasting guidelines available. In this article, an attempt is made to review these updated guidelines, as well as the current instructions for more controversial patients such as infants, the obese, and a particular type of ophthalmic surgery. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. The preoperative cardiology consultation: indications and risk modification.

    Science.gov (United States)

    Groot, M W; Spronk, A; Hoeks, S E; Stolker, R J; van Lier, F

    2017-11-01

    The cardiologist is regularly consulted preoperatively by anaesthesiologists. However, insights into the efficiency and usefulness of these consultations are unclear. This is a retrospective study of 24,174 preoperatively screened patients ≥18 years scheduled for elective non-cardiac surgery, which resulted in 273 (1%) referrals to the cardiologist for further preoperative evaluation. Medical charts were reviewed for patient characteristics, main reason for referring, requested diagnostic tests, interventions, adjustment in medical therapy, 30-day mortality and major adverse cardiac events. The most common reason for consultation was the evaluation of a cardiac murmur (95 patients, 35%). In 167 (61%) patients, no change in therapy was initiated by the cardiologist. Six consultations (2%) led to invasive interventions (electrical cardioversion, percutaneous coronary intervention or coronary artery bypass surgery). On average, consultation delayed clearance for surgery by two weeks. In most patients referred to the cardiologist after being screened at an outpatient anaesthesiology clinic, echocardiography is performed for ruling out specific conditions and to be sure that no further improvement can be made in the patient's health. In the majority, no change in therapy was initiated by the cardiologist. A more careful consideration about the potential benefits of consulting must be made for every patient.

  16. Slow desensitization of imatinib-induced nonimmediate reactions and dynamic changes of drug-specific CD4+CD25+CD134+ lymphocytes.

    Science.gov (United States)

    Klaewsongkram, Jettanong; Thantiworasit, Pattarawat; Sodsai, Pimpayao; Buranapraditkun, Supranee; Mongkolpathumrat, Pungjai

    2016-11-01

    Imatinib is a tyrosine kinase inhibitor indicated for the treatment of gastrointestinal stromal tumors (GISTs) and certain neoplastic diseases; however, nonimmediate adverse reactions are common. To describe the process of imatinib slow desensitization in patients who experienced nonimmediate reactions to imatinib and the dynamic change in drug-specific CD4 + CD25 + CD134 + T-lymphocyte percentages. Five patients diagnosed as having GISTs and with a recent history of imatinib-induced nonimmediate reactions (maculopapular exanthema with eosinophilia, exfoliative dermatitis, palmar-plantar erythrodysesthesia, and drug rash with eosinophilia and systemic symptoms) were desensitized using a slow desensitization protocol. The reintroduced imatinib dosage was stepped up every week starting from 10 mg/d and increasing to 25, 50, 75, 100, 150, 200, and 300 mg/d until the target dose of 400 mg/d was achieved. Prednisolone of up to 30 mg/d was allowed if allergic reactions recurred. The percentages of CD4 + CD25 + CD134 + T cells present after incubating peripheral blood mononuclear cells with imatinib, at baseline and after successful desensitization, were analyzed using flow cytometric analysis. By using a slow desensitization technique, all patients were able to receive 400 mg/d of imatinib, and prednisolone was gradually tapered off. The percentages of imatinib-induced CD4 + CD25 + CD134 + T cells decreased from a mean (SD) of 11.3% (6.5%) and 13.4% (7.3%) at baseline to 3.2% (0.7%) and 3.0% (1.1%) after successful desensitization, when stimulating peripheral blood mononuclear cells with 1 and 2 μM of imatinib, respectively. Slow desensitization is a helpful procedure in treating patients with imatinib-induced nonimmediate reactions other than simple maculopapular exanthema. The reduced percentages of imatinib-induced CD4 + CD25 + CD134 + T cells in these patients may be associated with immune tolerance. Copyright © 2016 American College of Allergy, Asthma & Immunology

  17. Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States.

    Science.gov (United States)

    Padula, William V; Larson, Richard A; Dusetzina, Stacie B; Apperley, Jane F; Hehlmann, Rudiger; Baccarani, Michele; Eigendorff, Ekkehard; Guilhot, Joelle; Guilhot, Francois; Hehlmann, Rudiger; Mahon, Francois-Xavier; Martinelli, Giovanni; Mayer, Jiri; Müller, Martin C; Niederwieser, Dietger; Saussele, Susanne; Schiffer, Charles A; Silver, Richard T; Simonsson, Bengt; Conti, Rena M

    2016-07-01

    We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs. We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct. Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP. © The Author 2016. Published by Oxford University Press.

  18. Preoperative biliary drainage for pancreatic cancer.

    Science.gov (United States)

    Van Heek, N T; Busch, O R; Van Gulik, T M; Gouma, D J

    2014-04-01

    This review is to summarize the current knowledge about preoperative biliary drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer. Most patients with pancreatic carcinoma (85%) will present with obstructive jaundice. The presence of toxic substances as bilirubin and bile salts, impaired liver function and altered nutritional status due to obstructive jaundice have been characterized as factors for development of complications after surgery. Whereas PBD was to yield beneficial effects in the experimental setting, conflicting results have been observed in clinical studies. The meta-analysis from relative older studies as well as more importantly a recent clinical trial showed that PBD should not be performed routinely. PBD for patients with a distal biliary obstruction is leading to more serious complications compared with early surgery. Arguments for PBD have shifted from a potential therapeutic benefit towards a logistic problem such as patients suffering from cholangitis and severe jaundice at admission or patients who need extra diagnostic tests, or delay in surgery due to a referral pattern or waiting list for surgery as well as candidates for neoadjuvant chemo(radio)therapy. If drainage is indicated in these patients it should be performed with a metal stent to reduce complications after the drainage procedure such as stent occlusion and cholangitis. Considering a change towards more neoadjuvant therapy regimes improvement of the quality of the biliary drainage concept is still important.

  19. The ultrastructure of tumor cells in patients with rectal cancer after pre-operative irradiation and intra-operative cryotherapy

    International Nuclear Information System (INIS)

    Vyinnik, Yu.O.; Kotenko, O.Je.; Nevzorov, V.P.; Chyibyisov, L.P.

    2000-01-01

    Electronic microscopy of the tumor cells was performed to confirm the efficacy of combined pre-operative gamma-therapy and intraoperative cryotherapy (CT). Pre-operative irradiation at the dose of 20 Gy accompanied by intra-operative cryotherapy caused the changes in the ultrastructure, the depth and degree of which allow to consider them destructive and irreversible

  20. The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse Testicular Normal Leydig Cells.

    Science.gov (United States)

    Kheradmand, Fatemeh; Hashemnia, Seyyed Mohammad Reza; Valizadeh, Nasim; Roshan-Milani, Shiva

    2016-01-01

    Growth factors play an essential role in the development of tumor and normal cells like testicular leydig cells. Treatment of cancer with anti-cancer agents like imatinib mesylate may interfere with normal leydig cell activity, growth and fertility through failure in growth factors' production or their signaling pathways. The purpose of the study was to determine cellular viability and the levels of, platelet derived growth factor (PDGF) and stem cell factor (SCF) in normal mouse leydig cells exposed to imatinib, and addressing the effect of imatinib on fertility potential. The mouse TM3 leydig cells were treated with 0 (control), 2.5, 5, 10 and 20 μM imatinib for 2, 4 and 6 days. Each experiment was repeated three times (15 experiments in each day).The cellular viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, one-way ANOVA with Tukey's post hoc and Kruskal-Wallis test were performed. A p-value less than 0.05 was considered statistically significant. With increasing drug concentration, cellular viability decreased significantly (pcellular viability, PDGF and SCF levels. Imatinib may reduce fertility potential especially at higher concentrations in patients treated with this drug by decreasing cellular viability. The effect of imatinib on leydig cells is associated with PDGF stimulation. Of course future studies can be helpful in exploring the long term effects of this drug.

  1. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.

    Science.gov (United States)

    Hughes, T P; Saglio, G; Quintás-Cardama, A; Mauro, M J; Kim, D-W; Lipton, J H; Bradley-Garelik, M B; Ukropec, J; Hochhaus, A

    2015-09-01

    BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247.

  2. Cytoprotective effect of imatinib mesylate in non-BCR-ABL-expressing cells along with autophagosome formation

    International Nuclear Information System (INIS)

    Ohtomo, Tadashi; Miyazawa, Keisuke; Naito, Munekazu; Moriya, Shota; Kuroda, Masahiko; Itoh, Masahiro; Tomoda, Akio

    2010-01-01

    Treatment with imatinib mesylate (IM) results in an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis. Electron microscopy revealed an increase of autophagosomes in response to IM. IM attenuated the cytotoxic effect of cytosine arabinoside, as well as inhibiting cell death with serum-deprived culture. Cytoprotection with autophagosome formation by IM was observed in various leukemia and cancer cell lines as well as normal murine embryonic fibroblasts (MEFs). Complete inhibition of autophagy by knockdown of atg5 in the Tet-off atg5 -/- MEF system attenuated the cytoprotective effect of IM, indicating that the effect is partially dependent on autophagy. However, cytoprotection by IM was not mediated through suppression of ROS production via mitophagy, ER stress via ribophagy, or proapoptotic function of ABL kinase. Although the target tyrosine kinase(s) of IM remains unclear, our data provide novel therapeutic possibilities of using IM for cytoprotection.

  3. Phase 1 study of INNO-406, a dual Abl/Lyn kinase inhibitor, in Philadelphia chromosome-positive leukemias after imatinib resistance or intolerance.

    Science.gov (United States)

    Kantarjian, Hagop; le Coutre, Phillipp; Cortes, Jorge; Pinilla-Ibarz, Javier; Nagler, Arnon; Hochhaus, Andreas; Kimura, Shinya; Ottmann, Oliver

    2010-06-01

    : INNO-406, a dual v-abl Abelson murine leukemia viral oncogene homolog (Abl)/v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog (Lyn) tyrosine kinase inhibitor (TKI), has demonstrated specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. Several breakpoint cluster region (Bcr)-Abl kinase domain mutations are sensitive to INNO-406 in vitro, including mutations that involve a phenylalanine-to-leucine or phenylalanine-to-valine substitution at codon 317 (F317L and F317V, respectively). In the current study, the authors evaluated the use of INNO-406 in patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) after imatinib resistance or intolerance. : A dose-escalation study was conducted at a starting dose of oral INNO-406 30 mg once daily. Cohorts of at least 3 patients were treated at each dose level until the maximum tolerated dose (MTD) was reached. Twice-daily dosing also was evaluated. Therapy was allowed to continue for a maximum of 24 months. : INNO-406 was administered to 56 patients with imatinib resistance (n = 40) or intolerance (n = 16). Other previous treatments included nilotinib (n = 20 patients), dasatinib (n = 26 patients), and dasatinib/nilotinib (n = 9 patients). Common mutations at the time of study entry included a tyrosine-to-histidine substitution at codon 253 (Y253H) (n = 6 patients), a glycine-to-glutamic acid substitution at codon 250 (G250E) (n = 4 patients), a threonine-to-isoleucine substitution at codon 315 (T315I) (n = 4 patients), and F317L (n = 3 patients). Of 31 patients with CML in chronic phase who received INNO-406, the major cytogenetic response rate was 19%. No responses were observed in patients who had CML in accelerated phase, CML in blastic phase, or Ph-positive ALL. The dose-limiting toxicities (DLTs) at an INNO-406 dose of 480 mg twice daily were liver function abnormalities and

  4. Comparison of the efficacy of preoperative X-ray and thermoradiotherapy used for the treatment of breast cancer

    International Nuclear Information System (INIS)

    Muravskaya, G.V.; Pantyushenko, T.A.; Fradkin, S.Z.; Zhavrid, Eh.A.; Moiseenko, V.V.

    1984-01-01

    An experience of the first randomatized clinical investigation on the usage of different variants of preoperative X-ray (with simultaneous local UHF hyperthepmia and without it) action in the case of combined treatment of patients with breast cancer has been summarized. It has been shown that conventional values of preoperative X-ray therapy (about 30-45 G.) are optimum ones. An increase of complex thermoradiotherapy efficacy in the case of considered cancer forms may be achieved at the expense of a stre gthening of preoperative X-ray action by means of dose increase up to the cancerogenic level or preoperative irradiation under the conditions of local UHF-hyperthermia

  5. Preoperative fasting time in children.

    LENUS (Irish Health Repository)

    Adeel, S

    2012-02-01

    The aim of preoperative fasting is to prevent regurgitation and pulmonary aspiration while limiting potential problems of thirst, dehydration and hypoglycaemia. The American Society of Anaesthesiologists (ASA) has suggested guidelines for preoperative fasting for children undergoing elective surgery. We did a postal survey to determine the current practice regarding these guidelines amongst all specialist registrars in anaesthesia in Ireland. A questionnaire was sent to all specialist registrars in anaesthesia (90 in total), 60 (67%) were returned and analysed. The question asked was how long children should be kept fasting before elective surgery. The results of our survey suggest that most of the respondents are following the ASA guidelines for clear fluids and solids however there were differing opinion regarding the duration of fasting for formula milk and breast milk. In conclusion, we would recommend greater awareness and collaboration between anaesthetists, nurses and surgeons to ensure that fasting instructions are consistent with the ASA guidelines and that patient and their parents understand these directives as well.

  6. Preoperative irradiation of hypernephroid carcinoma

    International Nuclear Information System (INIS)

    Akbar, D.

    1982-01-01

    Since 1969, preoperative irradiation of hypernephiroid carcinoma has been a routine measure at the Steglitz medical clinic: It consists in the application of a focal dose of 30 Gy, fractionated into doses of 2.5 Gy, as Betatron pendulum irradiation (42 MeV photons) covering the para-aortic lymph nodes. After a treatment-free interval of 3 weeks, radical nephrectomy is carried through. Of 178 patients, 47 were in tumor stage I, 15 in stage II, 83 in stage III and 33 in stage IV. In 99 patients the treatment dated back longer than 5 years; the survival rate was 52%. 67% of the patients had survived longer than 3 years. Operation lethality was 3%. The preoperative irradiation pursues the following aims: 1. Devitalization of potentially proliferating cells in the tumor periphery, and thus prevention of displaced tumor cells growing on and postoperative local recidivations; 2. Shrinking of the tumor, facilitating the surgical intervention. In a third of the cases a measurable alteration of the tumor was confirmed by X-ray. The low operation lethality of 3% is attributed to this. (orig./MG) [de

  7. Preoperative embolization of gigantic meningioma

    International Nuclear Information System (INIS)

    Wang Hongsheng; Chen Huaqun; Dong Congsong; Li Wenhui; Dai Zhenyu; Chen Guozhi

    2006-01-01

    Objective: To evaluate the clinical efficacy of preoperative embolization in treatment of patients with gigantic meningioma. Methods: Fourteen cases of gigantic meningioma diameter from 6 to 11 cm were measured by CT and MRI scan. DSA manifested that they are vascularizd meningioma and showed the mainly feeding arteries. We used getation sponge to superselectively embilized the feeding arteries. All tumors were performed surgical excision 3-7 days after the embolization. Results: DSA showed the blood supplies in the tumors in 9 cases were completely blocked, and that in 5 cases were dramatically eliminated. All patients were operated 3-7 days after the embolization. During the operations the bleeding were dramatically decreased and the operation time was shortened compared with those in unembolized cases. It helps us remove the tumors easy and quickly from the attachments. No complication occurred during and after the operations. Conclusion: Preoperative embolization of gigantic meningioma is a useful and relatively safe method in helping surgicaly and completely excised of tumor with significant reduction of blood loss and operation time. (authors)

  8. Preoperative embolization of facial angiomas

    International Nuclear Information System (INIS)

    Causmano, F.; Bruschi, G.; De Donatis, M.; Piazza, P.; Bassi, P.

    1988-01-01

    Preoperative embolization was performed on 27 patients with facial angiomas supplied by the external carotid branches. Sixteen were males and 11 females; 13 of these angiomas were high-flow arterio-venous (A-V), 14 were low-flow capillary malformations. Fourteen patients underwent surgical removal after preoperative embolization; in this group embolization was carried out with Spongel in 3 cases and with Lyodura in 11 cases. In 12 of these patients the last angiographic examination was performed 3-6 years later: angiography evidenced no recurrence in 8 cases (67%), while in 3 cases (25%) there was capillary residual angioma of negligible size. Treatment was unsuccessful in one patient only, due to the large recurrent A-V angioma. Thirteen patients underwent embolization only, which was carried out with Lyodura in 10 cases, and with Ivalon in 3 cases. On 12 of these patients the last angiographic study was performed 2-14 months later: there was recurrent A-V angioma in 5 patients (42%), who underwent a subsequent embolization; angiography evidenced no recurrence in the other 7 patients (58%). In both series, the best results were obtained in the patients with low-flow capillary angiomas. Embolization and subsequent surgical removal are the treatment of choice for facial angiomas; embolization alone is useful in the management of surgically inacessible vascular malformations, and it can be the only treatment in patients with small low-flow angiomas when distal occlusion of the feeding vessel with Lyodura or Ivalon particles is performed

  9. Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Randomized Phase 2 Trial of Neoadjuvant Preoperative Paclitaxel/Cisplatin/Radiation Therapy (RT) or Irinotecan/Cisplatin/RT in Esophageal Adenocarcinoma: Long-Term Outcome and Implications for Trial Design

    Energy Technology Data Exchange (ETDEWEB)

    Kleinberg, Lawrence R., E-mail: kleinla@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Harvard T.H. Chan School of Public Health, Boston, Massachusetts (United States); Forastiere, Arlene A. [Department of Oncology, Johns Hopkins University, Baltimore, Maryland (United States); Keller, Steven M. [Department of Cardiovascular and Thoracic Surgery, Montefiore Medical Center, Bronx, NY (United States); Mitchel, Edith P. [Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Anne, Pramila Rani [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Benson, Al B. [Department of Medicine-Hematology/Oncology, Lurie Cancer Center, Northwestern University, Chicago, Illinois (United States)

    2016-03-15

    Purpose: Toxicity, pathologic complete response, and long-term outcomes are reported for the neoadjuvant therapies assessed in a randomized phase 2 Eastern Cooperative Oncology Group and American College of Radiology Imaging Network trial for operable esophageal adenocarcinoma, staged as II-IVa by endoscopy/ultrasonography (EUS). Methods and Materials: A total of 86 eligible patients began treatment. For arm A, preoperative chemotherapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 50 mg/m{sup 2}, on day 1, 8, 22, 29 during 45 Gy radiation therapy (RT), 1.8 Gy per day over 5 weeks. Adjuvant therapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 65 mg/m{sup 2} day 1, 8 every 21 days for 3 cycles. Arm B therapy was cisplatin, 30 mg/m{sup 2}, and paclitaxel, 50 mg/m{sup 2}, day 1, 8, 15, 22, 29 with RT, followed by adjuvant cisplatin, 75 mg/m{sup 2}, and paclitaxel, 175 mg/m{sup 2}, day 1 every 21 days for 3 cycles. Stratification included EUS stage and performance status. Results: In arm A, median overall survival was 35 months, and 5-, 6-, and 7-year survival rates were 46%, 39%, and 35%, respectively, whereas for arm B, they were 21 months and 27%, 27%, and 23%, respectively. Median progression- or recurrence-free survival (PFS) was 39.8 months with a 3-year PFS of 50% for arm A and 12.4 months (P=.046) with 3-year PFS of 28% for arm B. Eighty percent of the observed incidents of progression occurred within 19 months. Survival did not differ significantly by EUS and performance status strata. Conclusions: Long-term survival was similar for both arms and did not appear superior to results achieved with other standard regimens.

  10. Expression of c-kit receptor in human cholangiocarcinoma and in vivo treatment with imatinib mesilate in chimeric mice

    Science.gov (United States)

    Kamenz, Thomas; Caca, Karel; Blüthner, Thilo; Tannapfel, Andrea; Mössner, Joachim; Wiedmann, Marcus

    2006-01-01

    AIM: To investigate the c-kit expression in biliary tract cancer cell lines and histological sections from patients with extrahepatic cholangiocarcinoma (CC) and to evaluate the efficacy of in vitro and in vitro treatment with imatinib mesilate. METHODS: The protein expression of c-kit in the human biliary tract cancer cell lines Mz-ChA-2 and EGI-1 and histological sections from 19 patients with extrahepatic CC was assessed by immunoblotting, immunocytochemistry, and immunohistochemistry. The anti-proliferative effect of imatinib mesilate on biliary tract cancer cell lines Mz-ChA-2 and EGI-1 was studied in vitro by automated cell counting. In addition, immunodeficient NMRI mice (TaconicTM) were subcutaneously injected with 5 x 106 cells of cell lines MzChA-2 and EGI-1. After having reached a tumour volume of 200 mm3, daily treatment was started intraperitoneally with imatinib mesilate at a dose of 50 mg/kg or normal saline (NS). Tumor volume was calculated with a Vernier caliper. After 14 d, mice were sacrificed with tumors excised and tumor mass determined. RESULTS: Immunoblotting revealed presence of c-kit in Mz-ChA-2 and absence in EGI-1 cells. Immunocytochemistry with c-kit antibodies displayed a cytoplasmatic and membraneous localization of receptor protein in Mz-ChA-2 cells and absence of c-kit in EGI-1 cells. c-kit was expressed in 7 of 19 (37%) extrahepatic human CC tissue samples, 2 showed a moderate and 5 a rather weak immunostaining. Imatinib mesilate at a low concentration of 5 µmol/L caused a significant growth inhibition in the c-kit positive cell line Mz-ChA-2 (31%), but not in the c-kit negative cell line EGI-1 (0%) (P < 0.05). Imatinib mesilate at an intermediate concentration of 10 µmol/L inhibited cellular growth of both cell lines (51% vs 57%). Imatinib mesilate at a higher concentration of 20 µmol/L seemed to have a general toxic effect on both cell lines. The IC50 values were 9.7 µmol/L and 11 µmol/L, respectively. After 14 d of in vitro

  11. Preoperative cryotherapy use in anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Koyonos, Loukas; Owsley, Kevin; Vollmer, Emily; Limpisvasti, Orr; Gambardella, Ralph

    2014-12-01

    Unrelieved postoperative pain may impair rehabilitation, compromise functional outcomes, and lead to patient dissatisfaction. Preemptive multimodal analgesic techniques may improve outcomes after surgery. We hypothesized that patients using preoperative cryotherapy plus a standardized postoperative treatment plan will have lower pain scores and require less pain medication compared with patients receiving a standardized postoperative treatment plan alone after arthroscopically assisted anterior cruciate ligament reconstruction (ACLR). A total of 53 consecutive patients undergoing arthroscopically assisted ACLR performed by one of seven surgeons were randomly assigned to one of two groups. Group 1 received no preoperative cryotherapy and group 2 received 30 to 90 minutes of preoperative cryotherapy to the operative leg using a commercial noncompressive cryotherapy unit. Visual analog scale pain scores and narcotic use were recorded for the first 4 days postoperatively. Total hours of cold therapy and continuous passive motion (CPM) use and highest degree of flexion achieved were recorded as well. Group 1 consisted of 26 patients (15 allograft Achilles tendon and 11 autograft bone patellar tendon bone [BPTB]), and group 2 consisted of 27 patients (16 allograft Achilles tendon and 11 autograft BPTB). Group 2 patients reported less pain (average 1.3 units, p cryotherapy, hours of CPM use, or maximum knee flexion achieved. Complications did not occur in either group. This is the first report we are aware of showing the postoperative effects of preoperative cryotherapy. Our results support the safety and efficacy of preoperative cryotherapy in a multimodal pain regimen for patients undergoing ACL reconstruction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis.

    Science.gov (United States)

    Shaker, Mohamed E; Zalata, Khaled R; Mehal, Wajahat Z; Shiha, Gamal E; Ibrahim, Tarek M

    2011-04-15

    Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl(4)) rat model. Male Wistar rats received intraperitoneal injections of CCl(4) twice weekly for 8weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20mg/kg), nilotinib (10 and 20mg/kg) and silymarin (100mg/kg) during the last 4weeks of CCl(4)-intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stress parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20mg/kg) was the most effective treatment to counteract CCl(4)-induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10mg/kg), nilotinib (20mg/kg) and silymarin (100mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl(4)-treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl(4)-induced fibrosis was ameliorated significantly by nilotinib (20mg/kg) and imatinib (20mg/kg). Unlike nilotinib, imatinib (20mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylin-eosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin.

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    Stephanie Morgan

    Full Text Available Chemotherapy treatment in premenopausal women has been linked to ovarian follicle loss and premature ovarian failure; the exact mechanism by which this occurs is uncertain. Here, two commonly used chemotherapeutic agents (cisplatin and doxorubicin were added to a mouse ovary culture system, to compare the sequence of events that leads to germ cell loss. The ability of imatinib mesylate to protect the ovary against cisplatin or doxorubicin-induced ovarian damage was also examined.Newborn mouse ovaries were cultured for a total of six days, exposed to a chemotherapeutic agent on the second day: this allowed for the examination of the earliest stages of follicle development. Cleaved PARP and TUNEL were used to assess apoptosis following drug treatment. Imatinib was added to cultures with cisplatin and doxorubicin to determine any protective effect.Histological analysis of ovaries treated with cisplatin showed oocyte-specific damage; in comparison doxorubicin preferentially caused damage to the granulosa cells. Cleaved PARP expression significantly increased for cisplatin (16 fold, p<0.001 and doxorubicin (3 fold, p<0.01. TUNEL staining gave little evidence of primordial follicle damage with either drug. Imatinib had a significant protective effect against cisplatin-induced follicle damage (p<0.01 but not against doxorubicin treatment.Cisplatin and doxorubicin both induced ovarian damage, but in a markedly different pattern, with imatinib protecting the ovary against damage by cisplatin but not doxorubicin. Any treatment designed to block the effects of chemotherapeutic agents on the ovary may need to be specific to the drug(s the patient is exposed to.

  14. Distinct Dasatinib-Induced Mechanisms of Apoptotic Response and Exosome Release in Imatinib-Resistant Human Chronic Myeloid Leukemia Cells

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    Juan Liu

    2016-04-01

    Full Text Available Although dasatinib is effective in most imatinib mesylate (IMT-resistant chronic myeloid leukemia (CML patients, the underlying mechanism of its effectiveness in eliminating imatinib-resistant cells is only partially understood. This study investigated the effects of dasatinib on signaling mechanisms driving-resistance in imatinib-resistant CML cell line K562 (K562RIMT. Compared with K562 control cells, exsomal release, the phosphoinositide 3-kinase (PI3K/protein kinase B (Akt/ mammalian target of rapamycin (mTOR signaling and autophagic activity were increased significantly in K562RIMT cells and mTOR-independent beclin-1/Vps34 signaling was shown to be involved in exosomal release in these cells. We found that Notch1 activation-mediated reduction of phosphatase and tensin homolog (PTEN was responsible for the increased Akt/mTOR activities in K562RIMT cells and treatment with Notch1 γ-secretase inhibitor prevented activation of Akt/mTOR. In addition, suppression of mTOR activity by rapamycin decreased the level of activity of p70S6K, induced upregulation of p53 and caspase 3, and led to increase of apoptosis in K562RIMT cells. Inhibition of autophagy by spautin-1 or beclin-1 knockdown decreased exosomal release, but did not affect apoptosis in K562RIMT cells. In summary, in K562RIMT cells dasatinib promoted apoptosis through downregulation of Akt/mTOR activities, while preventing exosomal release and inhibiting autophagy by downregulating expression of beclin-1 and Vps34. Our findings reveal distinct dasatinib-induced mechanisms of apoptotic response and exosomal release in imatinib-resistant CML cells.

  15. [The role of magnetic resonance imaging to select patients for preoperative treatment in rectal cancer].

    Science.gov (United States)

    Rödel, Claus; Sauer, Rolf; Fietkau, Rainer

    2009-08-01

    Traditionally, the decision to apply preoperative treatment for rectal cancer patients has been based on the T- and N-category. Recently, the radial distance of the tumor to the circumferential resection margin (CRM) has been identified as an important risk factor for local failure. By magnetic resonance imaging (MRI) this distance can be measured preoperatively with high reliability. Thus, selected groups have started to limit the indication for preoperative therapy to tumors extending to - or growing within 1 mm from - the mesorectal fascia (CRM+). Pros and cons of this selected approach for preoperative treatment and first clinical results are presented. Prerequisites are the availability of modern high-resolution thin-section MRI technology as well as strict quality control of MRI and surgical quality of total mesorectal excision (TME). By selecting patients with CRM-positive tumors on MRI for preoperative therapy, only approximately 35% patients will require preoperative radiotherapy (RT) or radiochemotherapy (RCT). However, with histopathologic work-up of the resected specimen after primary surgery, the indication for postoperative RCT is given for a rather large percentage of patients, i.e., for pCRM+ (5-10%), intramesorectal or intramural excision (30-40%), pN+ (30-40%). Postoperative RCT, however, is significantly less effective and more toxic than preoperative RCT. A further point of concern is the assertion that patients, in whom a CRM-negative status is achieved by surgery alone, do not benefit from additional RT. Data of the Dutch TME trial and the British MRC (Medical Research Council) CR07 trial, however, suggest the reverse. To omit preoperative RT/RCT for CRM-negative tumors on MRI needs to be further investigated in prospective clinical trials. The German guidelines for the treatment of colorectal cancer 2008 continue to indicate preoperative RT/RCT based on the T- and N-category.

  16. The role of magnetic resonance imaging to select patients for preoperative treatment in rectal cancer

    International Nuclear Information System (INIS)

    Roedel, Claus; Sauer, Rolf; Fietkau, Rainer

    2009-01-01

    Background: Traditionally, the decision to apply preoperative treatment for rectal cancer patients has been based on the T- and N-category. Recently, the radial distance of the tumor to the circumferential resection margin (CRM) has been identified as an important risk factor for local failure. By magnetic resonance imaging (MRI) this distance can be measured preoperatively with high reliability. Thus, selected groups have started to limit the indication for preoperative therapy to tumors extending to - or growing within 1 mm from - the mesorectal fascia (CRM+). Methods: Pros and cons of this selected approach for preoperative treatment and first clinical results are presented. Prerequisites are the availability of modern high-resolution thin-section MRI technology as well as strict quality control of MRI and surgical quality of total mesorectal excision (TME). Results: By selecting patients with CRM-positive tumors on MRI for preoperative therapy, only approximately 35% patients will require preoperative radiotherapy (RT) or radiochemotherapy (RCT). However, with histopathologic work-up of the resected specimen after primary surgery, the indication for postoperative RCT is given for a rather large percentage of patients, i.e., for pCRM+ (5-10%), intramesorectal or intramural excision (30-40%), pN+ (30-40%). Postoperative RCT, however, is significantly less effective and more toxic than preoperative RCT. A further point of concern is the assertion that patients, in whom a CRM-negative status is achieved by surgery alone, do not benefit from additional RT. Data of the Dutch TME trial and the British MRC (Medical Research Council) CR07 trial, however, suggest the reverse. Conclusion: To omit preoperative RT/RCT for CRM-negative tumors on MRI needs to be further investigated in prospective clinical trials. The German guidelines for the treatment of colorectal cancer 2008 continue to indicate preoperative RT/RCT based on the T- and N-category. (orig.)

  17. Preoperative patient education: evaluating postoperative patient outcomes.

    Science.gov (United States)

    Meeker, B J

    1994-04-01

    Preoperative teaching is an important part of patient care and can prevent complications, as well as promote patient fulfillment during hospitalization. A study was conducted at Alton Ochsner Medical Foundation in New Orleans, LA, in 1989, to determine the impact of a preoperative teaching program on the incidence of postoperative atelectasis and patient satisfaction. Results showed no significant difference of postoperative complications and patient gratification after participating in a structured preoperative teaching program. As part of this study, it was identified that a patient evaluation tool for a preoperative teaching class needed to be developed. The phases of this process are explained in the following article.

  18. Fluid retention associated with imatinib treatment in patients with gastroenterol stromal: Quantitative radiologic assessment and implications for management

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Won; Shinagare, Atul B.; Krajewski, Katherine M.; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikihil H. [Dept. of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Harvard Medical School, Boston (United States); Pyo, Jun Hee [The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston (United States)

    2015-04-15

    We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.

  19. The management of invasive transitional cell carcinoma of the bladder. Results of definitive and preoperative radiation therapy in 390 patients treated at the Prince of Wales Hospital, Sydney, Australia.

    Science.gov (United States)

    Mameghan, H; Fisher, R J; Watt, W H; Meagher, M J; Rosen, I M; Mameghan, J; Brook, S; Tynan, A P; Korbel, E I; Millard, R J

    1992-06-01

    The treatment results for invasive transitional cell carcinoma (TCC) of the bladder were assessed in a series of 390 patients referred to the Department of Radiation Oncology at the Prince of Wales Hospital, Sydney, Australia, during the period 1977 to 1988. These patients were managed by one of two strategies: cystectomy (87 patients) and radiation therapy (303 patients). Actuarial survival rates (death from any cause) were determined and comparisons were made using log-rank tests and Cox regression analyses. The mean follow-up time was 7.6 years. Independent prognostic factors for shorter survival were: the presence of a ureteric obstruction (P less than 0.001), increasing clinical stage (P less than 0.001), increasing patient age (P = 0.003), and earlier year of presentation (P = 0.008). Comparison of the two strategies indicated no significant difference in overall survival after adjusting for imbalances in prognostic factors (P = 0.007 unadjusted; P = 0.29 adjusted). The slightly longer survival of 46 patients from 1983 onward who received primary systemic chemotherapy (compared with 149 patients not given chemotherapy) was not statistically significant (P = 0.12 unadjusted; P = 0.56 adjusted for prognostic factors). The 5-year actuarial rates of severe complications were 8.0% after cystectomy and 5.3% after radiation therapy. In 303 patients treated by definitive radiation therapy, the 5-year actuarial rate of freedom from bladder failure for all clinical tumor stages was 44% (Tx, 67%; T1, 45%; T2, 56%; T3, 39%; and T4, 39%). These results suggest that definitive radiation therapy is a viable alternative to radical cystectomy for patients with invasive TCC of the bladder.

  20. Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

    Science.gov (United States)

    Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

    2015-06-01

    Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

  1. Up regulation of K A I 1 gene expression and apoptosis effect of imatinib mesylate in gastric adenocarcinoma (AGS cell line

    Directory of Open Access Journals (Sweden)

    eyed Ataollah Sadat Shandiz

    2016-02-01

    Full Text Available Objective: To evaluate the effect of imatinib mesylate on KAI1 gene expression and apoptosis properties in human gastric carcinoma AGS cell line. Methods: Cell viability was assessed by MTT assay and quantitative real time PCR method was applied for investigation of Bax, Bcl-2, and KAI1 gene expression in AGS cells. The quantity of KAI1, Bax, and Bcl-2 compared to GAPDH gene expressions were examined using the formula 2-∆∆Ct. Furthermore, cell apoptosis/necrosis was carried out by annexin V/PI staining and quantified with flow cytometry after treatment with imatinib. Results: Imatinib mesylate was showed to have a dose-dependent toxicity effect against AGS cells. KAI1/GAPDH gene expression ratios were 1.07 ± 0.02 (P > 0.05, 1.68 ± 0.19 (P > 0.05, 3.60 ± 0.55 (P < 0.05, 6.54 ± 0.27 (P < 0.001 for 20, 50, 80 and 100 μmol/L of imatinib concentrations. The mRNA levels of Bax detected by real-time PCR after treatment with imatinib mesylate were significantly increased. Also, the number of apoptotic cells was increased from 3.72% (statistically significant; P < 0.05 in untreated AGS cells to 21.72%, 83.04% and 85.80%, respectively, following treatment with 20, 40, and 60 μmol/L imatinib mesylate. Conclusions: The results suggest that imatinib mesylate can induce apoptosis pathway in a dose-dependent mode and might modulate metastasis by up regulating KAI1 gene expression in human gastric carcinoma AGS cell line.

  2. Three Paths to Better Tyrosine Kinase Inhibition Behind the Blood-Brain Barrier in Treating Chronic Myelogenous Leukemia and Glioblastoma with Imatinib

    Science.gov (United States)

    Kast, Richard E; Focosi, Daniele

    2010-01-01

    Chronic myelogenous leukemia (CML) can be controlled for years with the tyrosine kinase inhibitor imatinib but because imatinib poorly penetrates the blood-brain barrier (BBB), on occasion, the CML clone will thrive and evolve to an accelerated phase in the resulting imatinib sanctuary within the central nervous system. In this, CML resembles glioblastoma in that imatinib, which otherwise may be effective, cannot get to the tumor. Although a common street drug of abuse, methamphetamine is Food and Drug Administration-approved and marketed as a pharmaceutical drug to treat attention-deficit disorders. It has shown the ability to open the BBB in rodents. We have some clinical hints that it may do so in humans as well. This short note presents three new points potentially leading to better tyrosine kinase inhibition behind the BBB: 1) Pharmaceutical methamphetamine may have a useful role in treating both CML and glioblastoma by allowing higher imatinib concentrations behind the BBB. 2) The old antidepressant and monoamine oxidase inhibitor selegiline, used to treat Parkinson disease, is catabolized to methamphetamine. Selegiline, as a nonscheduled drug,may therefore be an easier way to open the BBB, allowing more effective chemotherapy with tyrosine kinases. 3) Dasatinib is a tyrosine kinase inhibitor with a spectrum of inhibition only partially overlapping that of imatinib and a mechanism of tyrosine kinase inhibition that is different from that of imatinib. The two should be additive. In addition, dasatinib crosses the BBB poorly, and it can therefore be expected to benefit from methamphetamine-assisted entry. PMID:20165690

  3. Preoperative evaluation of locally spreaded pelvic tumors

    International Nuclear Information System (INIS)

    Baramia, M.; Todua, F.; Gotsadze, D.; Khutulashvili, N.; Lashkhi, K.; Nadareishvili, A.

    1998-01-01

    Am of the study: preoperative evaluation of patients with locally advanced pelvic tumors subjected to pelvic exenteration. Determine operability to avoid explorative laparatomies, which cause serious complications in these patients. Evaluate condition of urinary system in case of this pathology. Materials and methods: 34 patients with locally advanced pelvic tumors where pelvic exenteration was attempted were studied. Along with other methods of diagnostic CT and MRI were performed. Results: In all patients secondary involvement of the urinary bladder was noted. In 30 patients CT and MR findings were confirmed (88,2%) intraoperatively and different types of pelvic organs exenteration were performed. In 1 case spread of tomoruos infiltrate to the pelvic wall and common iliac vessels was detected intraoperatively (patient had history of radiation therapy). In 2 cases carcinomatosis of the peritoneum was found. In 1 case involvement of urinary bladder was simulated by close attachment of enlarged uterus. Conclusion: Obtained results show, that CT and MR are highly informative methods of disease spread evaluation and thus determining operability. Radiotherapy performed prior to operation sets difficulties in differentiation for tumourous infiltrate and post-radiotherapy changes in pelvis. (Full text)

  4. Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis

    International Nuclear Information System (INIS)

    Shaker, Mohamed E.; Zalata, Khaled R.; Mehal, Wajahat Z.; Shiha, Gamal E.; Ibrahim, Tarek M.

    2011-01-01

    Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl 4 ) rat model. Male Wistar rats received intraperitoneal injections of CCl 4 twice weekly for 8 weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20 mg/kg), nilotinib (10 and 20 mg/kg) and silymarin (100 mg/kg) during the last 4 weeks of CCl 4 -intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stress parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20 mg/kg) was the most effective treatment to counteract CCl 4 -induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10 mg/kg), nilotinib (20 mg/kg) and silymarin (100 mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl 4 -treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl 4 -induced fibrosis was ameliorated significantly by nilotinib (20 mg/kg) and imatinib (20 mg/kg). Unlike nilotinib, imatinib (20 mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylin-eosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans. - Graphical abstract: Display Omitted Research Highlights: → The anti-fibrotic effects of imatinib, nilotinib and silymarin were compared. → These effects were

  5. The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate.

    Science.gov (United States)

    Lee, Sung-Eun; Choi, Soo Young; Bang, Ju-Hee; Kim, Soo-Hyun; Jang, Eun-Jung; Byeun, Ji-Young; Park, Jin Eok; Jeon, Hye-Rim; Oh, Yun Jeong; Kim, Myungshin; Kim, Dong-Wook

    2012-11-01

    The aim of this study was to evaluate the long-term clinical significance of an additional chromosomal abnormality (ACA), variant Philadelphia chromosome (vPh) at diagnosis, and newly developed other chromosomal abnormalities (OCA) in patients with chronic myeloid leukemia (CML) on imatinib (IM) therapy. Sequential cytogenetic data from 281 consecutive new chronic phase CML patients were analyzed. With a median follow-up of 78.6 months, the 22 patients with vPh (P = 0.034) or ACA (P = 0.034) at diagnosis had more events of IM failure than did the patients with a standard Ph. The 5-year overall survival (OS), event-free survival (EFS), and failure-free survival (FFS) rates for patients with vPh at diagnosis were 77.8%, 75.0%, and 53.3%, respectively; for patients with ACA at diagnosis, 100%, 66.3%, and 52.1%, respectively; and for patients with a standard Ph, 96.0%, 91.3%, and 83.7%, respectively. During IM therapy, eight patients developed an OCA, which had no impact on outcomes as a time-dependent covariate in our Cox proportional hazards regression models. This study showed that vPh was associated with poor OS and FFS and that ACA had adverse effects on EFS and FFS. In addition, no OCA, except monosomy 7, had any prognostic impact, suggesting that the development of OCA may not require a change in treatment strategy. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Preoperative treatment of rectum cancers

    International Nuclear Information System (INIS)

    Mineur, L.; Serin, D.; Chauvet, B.; Reboul, F.; Molinari, N.; Guyot, T.; Ciornea, D.; Leignel, D.L.; Chapet, L.C.; Garaud, P.G.; Calais, G.C.; Calan, L.D.C. de; Viguier, J.V.; Boukerche, A.; Bechekat, C.; Dali-Youcef, A.F.; Larbaoui, B.; Djellali, L.; Safir, A.; Albarghach, M.N.; Malhaire, J.P.; Bouchekoua, M.; Muller, M.; Metges, J.P.; Pradier, O.; Robaszkiewicz, M.

    2007-01-01

    Five articles treat the question of rectum carcinoma through a combined therapy that associates radiotherapy ( pre or post operative), chemotherapy (concomitant before surgery) and surgery. The local control is also considered. (N.C.)

  7. Efficacy of Acupuncture in Reducing Preoperative Anxiety: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Hyojeong Bae

    2014-01-01

    Full Text Available Background. Acupuncture has been shown to reduce preoperative anxiety in several previous randomized controlled trials (RCTs. In order to assess the preoperative anxiolytic efficacy of acupuncture therapy, this study conducted a meta-analysis of an array of appropriate studies. Methods. Four electronic databases (MEDLINE, EMBASE, CENTRAL, and CINAHL were searched up to February 2014. In the meta-analysis data were included from RCT studies in which groups receiving preoperative acupuncture treatment were compared with control groups receiving a placebo for anxiety. Results. Fourteen publications (N = 1,034 were included. Six publications, using the State-Trait Anxiety Inventory-State (STAI-S, reported that acupuncture interventions led to greater reductions in preoperative anxiety relative to sham acupuncture (mean difference = 5.63, P < .00001, 95% CI [4.14, 7.11]. Further eight publications, employing visual analogue scales (VAS, also indicated significant differences in preoperative anxiety amelioration between acupuncture and sham acupuncture (mean difference = 19.23, P < .00001, 95% CI [16.34, 22.12]. Conclusions. Acupuncture therapy aiming at reducing preoperative anxiety has a statistically significant effect relative to placebo or nontreatment conditions. Well-designed and rigorous studies that employ large sample sizes are necessary to corroborate this finding.

  8. Impaired anastomotic healing after preoperative radiotherapy ...

    African Journals Online (AJOL)

    Background. Patients with rectal carcinoma undergoing total mesorectal excision (TME) have a lower recurrence rate with preoperative radiotherapy (RT). The aim of this study was to assess the side-effects in patients who had preoperative RT compared with those who did not receive it (because of palliative resections, ...

  9. Preoperative Smoking Status and Postoperative Complications

    DEFF Research Database (Denmark)

    Pedersen, Marie Grønkjær; Eliasen, Marie; Skov-Ettrup, Lise Skrubbeltrang

    2014-01-01

    To systematically review and summarize the evidence of an association between preoperative smoking status and postoperative complications elaborated on complication type.......To systematically review and summarize the evidence of an association between preoperative smoking status and postoperative complications elaborated on complication type....

  10. Imatinib-induced fulminant liver failure in chronic myeloid leukemia: role of liver transplant and second-generation tyrosine kinase inhibitors: a case report.

    Science.gov (United States)

    Nacif, Lucas Souto; Waisberg, Daniel R; Pinheiro, Rafael Soares; Lima, Fabiana Roberto; Rocha-Santos, Vinicius; Andraus, Wellington; D'Albuquerque, Luiz Carneiro

    2018-03-10

    There is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading transplant centers in evaluating imatinib-induced acute liver failure in chronic myeloid leukemia and follow-up in liver transplantation. A 36-year-old brown-skinned woman (mixed Brazilian race) diagnosed 1 year earlier with chronic myeloid leukemia was started after delivery of a baby and continued for 6 months with imatinib mesylate (selective inhibitor of Bcr-Abl tyrosine kinase), which induced liver failure. We conducted a literature review using the PubMed database for articles published through September 2017, and we demonstrate a role of liver transplant in this situation for imatinib-induced liver failure. We report previously published results and a successful liver transplant after acute liver failure due to imatinib-induced in chronic myeloid leukemia treatment. We report a case of a successful liver transplant after acute liver failure resulting from imatinib-induced chronic myeloid leukemia treatment. The literature reveals the importance of prompt acute liver failure diagnosis and treatment with liver transplant in selected cases.

  11. The mTOR inhibitor, everolimus (RAD001), overcomes resistance to imatinib in quiescent Ph-positive acute lymphoblastic leukemia cells

    International Nuclear Information System (INIS)

    Kuwatsuka, Y; Minami, M; Minami, Y; Sugimoto, K; Hayakawa, F; Miyata, Y; Abe, A; Goff, D J; Kiyoi, H; Naoe, T

    2011-01-01

    In Ph-positive (Ph + ) leukemia, the quiescent cell state is one of the reasons for resistance to the BCR-ABL-kinase inhibitor, imatinib. In order to examine the mechanisms of resistance due to quiescence and the effect of the mammalian target of rapamycin inhibitor, everolimus, for such a resistant population, we used Ph + acute lymphoblastic leukemia patient cells serially xenotransplanted into NOD/SCID/IL2rγ null (NOG) mice. Spleen cells from leukemic mice showed a higher percentage of slow-cycling G 0 cells in the CD34 + CD38 − population compared with the CD34 + CD38 + and CD34 − populations. After ex vivo imatinib treatment, more residual cells were observed in the CD34 + CD38 − population than in the other populations. Although slow-cycling G 0 cells were insensitive to imatinib in spite of BCR-ABL and CrkL dephosphorylation, combination treatment with everolimus induced substantial cell death, including that of the CD34 + CD38 − population, with p70-S6 K dephosphorylation and decrease of MCL-1 expression. The leukemic non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse system with the in vivo combination treatment with imatinib and everolimus showed a decrease of tumor burden including CD34 + cells. These results imply that treatment with everolimus can overcome resistance to imatinib in Ph + leukemia due to quiescence

  12. FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia: A Low-Burden Disease with Dramatic Response to Imatinib - A Report of 5 Cases from South India

    Directory of Open Access Journals (Sweden)

    Anıl Kumar N.

    2014-12-01

    Full Text Available OBJECTIVE: Eosinophilia associated with FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukemia and affected patients are sensitive to imatinib treatment. This study was undertaken to learn the prevalence and associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 26 adult patients presenting with profound eosinophilia (>1.5x109/L. METHODS: Reverse-transcriptase polymerase chain reaction and gel electrophoresis were used for the detection of FIP1L1-PDGFRA rearrangement. RESULTS: Five male patients with splenomegaly carried the FIP1L1-PDGFRA gene rearrangement. All patients achieved complete hematological response within 4 weeks of starting imatinib. One patient had previous deep vein thrombosis and 1 patient had cardiomyopathy, which improved with steroids and imatinib. Conventional cytogenetics was normal in all these patients. No primary resistance to imatinib was noted. CONCLUSION: This study indicates the need to do the FIP1L1-PDGFRA assay in patients with hypereosinophilic syndrome. Prompt treatment of this condition with imatinib can lead to complete hematological response and resolution of the organ damage that can be seen in this setting.

  13. Can preoperative electrical nociceptive stimulation predict acute pain after groin herniotomy?

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Hansen, J.B.; Kehlet, H.

    2008-01-01

    Preoperative identification of patients at risk for high-intensity postoperative pain may be used to predict patients at risk for development of a persistent pain state and allocate patients to more intensive specific pain therapy. Preoperative pain threshold to electrocutaneus stimulation has...... repair. The correlation between the pain data for electrical stimulation was compared with the postoperative pain during the first week in 165 patients, whereof 3 were excluded. Preoperative electrical pain detection threshold and electrical pain tolerance threshold did not correlate to postoperative...... pain (rho = -0.13, P = .09, and rho = -1.2, P = .4, respectively. PERSPECTIVE: Although preoperative electrical nociceptive stimulation may predict patients at risk of high-intensity acute pain after other surgical procedures, this was not the case in groin hernia repair patients receiving concomitant...

  14. Preoperative radium therapy and radical hysterectomy in the treatment of cervical cancer stage IB, IIA, and initial IIB.; Radiumterapia pre-operatoria e histerectomia radical no tratamento do cancer do colo uterino IB, IIA e IIB inicial

    Energy Technology Data Exchange (ETDEWEB)

    Salum, Resalla; Lopes, Edison R.; Souza, Maria A.H. de [Faculdade de Medicina do Triangulo Mineiro, Uberaba, MG (Brazil). Hospital Escola

    1995-07-01

    Patients with IB, IIa and in initial IIb cervical cancer were randomized for combined therapy, consisting of one or two radium insertion followed by Wertheim Meigs operation performed 40 days later. We look for the early and late complications of the treatment, residual cancer after radiotherapy and survival without recurrence. The project begin in 1965 and ended in 1986. All the operations were done by one of the investigators and 116 patients were analysed. The age ranged from 21 to 75 years with an average of 4.18 years. During the operations 31 (26.72%) patients needed 1.500 cc or greater amount of blood transfusion and we have 3 iliac veins lesions. Managing the ureters, we do our best to leave the posterior fascia as intact as possible. Post operative complications ranged from minor (fever, localised pelvic infections, temporary popliteal nerve paralysis) to evisceration (3 patients) deep venous thrombosis (3 patients) and two early urinary fistulas. Late complications were seen in patients submitted to sequential teletherapy irradiation. One uretrovaginal fistula occurred 10 month after treatment, another one, 7 years later and the third one 24 years later. One patient develop hydronefrosis and enterocolite after 7.000 rads of teletherapy and another one rectovaginal fistula 13 years after initial therapy. The shortening of the vagina making impossible the intercourse was seen in 7 patients. By the histological examination, the cervix was sterilized in 73.3 % of the patients. Residual cancer was found according the original size of the tumour and the stage of the disease. Studying different combinations between the existence of residual cervical cancer with positive or negative limphnodes and making a correlation with survival, we found the critical points is to have positive cervix and positive lymphonodes. The five years survival (life table methodology) for stage 1 lesion was 96%; stage II, 67%. At ten years survival was slighted different. With positive

  15. MR images of oral cancer treated with preoperative radiotherapy

    International Nuclear Information System (INIS)

    Onizawa, Kojiro; Niitsu Mamoru; Yusa, Hiroshi; Yanagawa, Toru; Yoshida, Hiroshi

    2003-01-01

    This study was carried out to evaluate the relationship between the effect of preoperative radiotherapy for oral cancer and the changes of signal intensity with MR images. T2-weighted images were compared before and after radiotherapy in 18 patients with primary oral cancer, and the effect on the lesions was histologically evaluated in surgically resected specimens obtained four weeks after the therapy. The MR images showed significantly decreased signal intensity of the lesions. The decrease of signal intensity was remarkable starting at two weeks after completion of the radiotherapy, compared with the decrease at less than two weeks after the therapy. The change of signal intensity was more obvious in tongue cancer than in other oral cancers. There was no significant difference in the change of the signal intensity between cancers with histologically poor response to the therapy and those with good response. These results suggested that signal intensity of oral cancer on T2-weighted images showed a significant decrease after preoperative radiotherapy, and that the intensity could be affected by duration after radiotherapy and primary sites. (author)

  16. Association of preoperative radiation effect with tumor angiogenesis and vascular endothelial growth factor in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Shintani, Satoru; Kiyota, Akihisa; Mihara, Mariko; Nakahara, Yuuji; Terakado, Nagaaki; Ueyama, Yoshiya; Matsumura, Tomohiro

    2000-01-01

    This study examined the relationship between tumor angiogenesis and the radiation-induced response, evaluated based on pathological changes, in oral squamous cell carcinoma patients treated with preoperative radiation therapy. Forty-one cases of squamous cell carcinoma treated with preoperative radiation therapy were investigated. Tumor angiogenesis was assessed by scoring the intratumor microvessel density (IMVD). Expression of vascular endothelial growth factor (VEGF) was also evaluated before and after preoperative radiotherapy. There was no correlation between IMVD in the specimens before therapy and the pathological response to radiation therapy. However, radiation therapy decreased IMVD in the specimens after therapy. A significant association was observed between VEGF expression and resistance to radiation therapy: only 4 of the 21 patients whose tumors exhibited a high level (2+ or 3+) of VEGF staining experienced a major (3+ or 4+) pathological response to radiation therapy. Furthermore, an increasing level of VEGF expression after radiation therapy was observed in non-effective (0 to 2+) response cases. These results suggest that VEGF expression and the induction of this protein are related to radiosensitivity and could be used to predict the effects of preoperative radiation therapy on oral squamous cell carcinoma. (author)

  17. Preoperative biliary drainage in hilar cholangiocarcinoma: When and how?

    Science.gov (United States)

    Paik, Woo Hyun; Loganathan, Nerenthran; Hwang, Jin-Hyeok

    2014-01-01

    Hilar cholangiocarcinoma is a tumor of the extrahepatic bile duct involving the left main hepatic duct, the right main hepatic duct, or their confluence. Biliary drainage in hilar cholangiocarcinoma is sometimes clinically challenging because of complexities associated with the level of biliary obstruction. This may result in some adverse events, especially acute cholangitis. Hence the decision on the indication and methods of biliary drainage in patients with hilar cholangiocarcinoma should be carefully evaluated. This review focuses on the optimal method and duration of preoperative biliary drainage (PBD) in resectable hilar cholangiocarcinoma. Under certain special indications such as right lobectomy for Bismuth type IIIA or IV hilar cholangiocarcinoma, or preoperative portal vein embolization with chemoradiation therapy, PBD should be strongly recommended. Generally, selective biliary drainage is enough before surgery, however, in the cases of development of cholangitis after unilateral drainage or slow resolving hyperbilirubinemia, total biliary drainage may be considered. Although the optimal preoperative bilirubin level is still a matter of debate, the shortest possible duration of PBD is recommended. Endoscopic nasobiliary drainage seems to be the most appropriate method of PBD in terms of minimizing the risks of tract seeding and inflammatory reactions. PMID:24634710

  18. Preoperative concurrent CBDCA chemotherapy and accelerated hyperfractionated radiotherapy for squamous cell carcinoma of the maxillary region

    International Nuclear Information System (INIS)

    Omura, Ken; Harada, Hiroyuki; Suzuki, Haruhiko; Takeuchi, Yosuke; Hatano, Kazuo; Togawa, Takashi

    2001-01-01

    Between 1994 and 2000, 28 patients with T3/T4 squamus cell carcinoma of the maxillary region (maxillary sinus, 22; maxillary gingiva, 4; maxillary bone, 1; buccal mucosa, 1) had accelerated hyperfractionated radiotherapy combined with simultaneous CBDCA chemotherapy preoperatively, at Chiba Cancer Center Hospital. The protocol consisted of combined therapy with accelerated hyperfractionated irradiation of 1.6 Gy, twice a day, to a total dose of 32.0-51.2 Gy and concurrent intra-arterial or intravenous infusion of CBDCA 20-30 mg/body/day for a cumulative total dose of 270-480 mg. After completion of the preoperative combined therapy, the clinical CR rate was 17.9%, and the good PR·CR rate was 32.1%. According to the initial findings and response to the combined therapy, all patients had maxillectomy (subtotal, 3; total, 16; extended, 9) 4 weeks after completion of the preoperative combined therapy. Postoperatively, the complete pathologic response (Ohboshi and Shimozato's classification, grade III and IV) rate was 28.6%. And the actuarial local control rate was 85.7%, with a mean follow-up of 46.2 months. Based on these results, we believe this preoperative therapy with CBDCA chemotherapy and accelerated hyperfractionated radiation is a significant choice as treatment for squamous cell cancer of the maxillary region. (author)

  19. Preoperative concurrent CBDCA chemotherapy and accelerated hyperfractionated radiotherapy for squamous cell carcinoma of the maxillary region

    Energy Technology Data Exchange (ETDEWEB)

    Omura, Ken; Harada, Hiroyuki [Tokyo Medical and Dental Univ. (Japan). Graduate School; Suzuki, Haruhiko; Takeuchi, Yosuke; Hatano, Kazuo; Togawa, Takashi

    2001-11-01

    Between 1994 and 2000, 28 patients with T3/T4 squamus cell carcinoma of the maxillary region (maxillary sinus, 22; maxillary gingiva, 4; maxillary bone, 1; buccal mucosa, 1) had accelerated hyperfractionated radiotherapy combined with simultaneous CBDCA chemotherapy preoperatively, at Chiba Cancer Center Hospital. The protocol consisted of combined therapy with accelerated hyperfractionated irradiation of 1.6 Gy, twice a day, to a total dose of 32.0-51.2 Gy and concurrent intra-arterial or intravenous infusion of CBDCA 20-30 mg/body/day for a cumulative total dose of 270-480 mg. After completion of the preoperative combined therapy, the clinical CR rate was 17.9%, and the good PR{center_dot}CR rate was 32.1%. According to the initial findings and response to the combined therapy, all patients had maxillectomy (subtotal, 3; total, 16; extended, 9) 4 weeks after completion of the preoperative combined therapy. Postoperatively, the complete pathologic response (Ohboshi and Shimozato's classification, grade III and IV) rate was 28.6%. And the actuarial local control rate was 85.7%, with a mean follow-up of 46.2 months. Based on these results, we believe this preoperative therapy with CBDCA chemotherapy and accelerated hyperfractionated radiation is a significant choice as treatment for squamous cell cancer of the maxillary region. (author)

  20. Proliferation of Interstitial Cells in the Cyclophosphamide-Induced Cystitis and the Preventive Effect of Imatinib

    Directory of Open Access Journals (Sweden)

    Maria Sancho

    2017-01-01

    Full Text Available Cyclophosphamide- (CYP- induced cystitis in the rat is a well-known model of bladder inflammation that leads to an overactive bladder, a process that appears to involve enhanced nitric oxide (NO production. We investigated the changes in the number and distribution of interstitial cells (ICs and in the expression of endothelial NO synthase (eNOS in the bladder and urethra of rats subjected to either intermediate or chronic CYP treatment. Pronounced hyperplasia and hypertrophy of ICs were evident within the lamina propria and in the muscle layer. IC immunolabeling with CD34, PDGFRα, and vimentin was enhanced, as reflected by higher colocalization indexes of the distinct pairs of markers. Moreover, de novo expression of eNOS was evident in vimentin and CD34 positive ICs. Pretreatment with the receptor tyrosine kinase inhibitor Imatinib prevented eNOS expression and ICs proliferation, as well as the increased voiding frequency and urinary tract weight provoked by CYP. As similar results were obtained in the urethra, urethritis may contribute to the uropathology of CYP-induced cystitis.

  1. Survival of gastrointestinal stromal tumor patients in the imatinib era: life raft group observational registry.

    Science.gov (United States)

    Call, Jerry; Walentas, Christopher D; Eickhoff, Jens C; Scherzer, Norman

    2012-03-19

    Gastrointestinal stromal tumors (GIST), one of the most common mesenchymal tumors of the gastrointestinal tract, prior to routine immunohistochemical staining and the introduction of tyrosine kinase inhibitors, were often mistaken for neoplasms of smooth muscle origin such as leiomyomas, leiomyosarcomas or leiomyoblastomas. Since the advent of imatinib, GIST has been further delineated into adult- (KIT or PDGFRα mutations) and pediatric- (typified by wild-type GIST/succinate dehydrogenase deficiencies) types. Using varying gender ratios at age of diagnosis we sought to elucidate prognostic factors for each sub-type and their impact on overall survival. This is a long-term retrospective analysis of a large observational study of an international open cohort of patients from a GIST research and patient advocacy's lifetime registry. Demographic and disease-specific data were voluntarily supplied by its members from May 2000-October 2010; the primary outcome was overall survival. Associations between survival and prognostic factors were evaluated by univariate Cox proportional hazard analyses, with backward selection at P diligence be taken with "young adults" (aged 18-35 at diagnosis) as pediatric-type GIST may present well beyond adolescence, particularly as these distinct sub-types have different causes, and consequently respond differently to treatments.

  2. Preoperative renal function and surgical outcomes in patients with acute type A aortic dissection†.

    Science.gov (United States)

    Imasaka, Ken-ichi; Tayama, Eiki; Tomita, Yukihiro

    2015-04-01

    There are few data concerning the impact of preoperative renal function, assessed using estimated glomerular filtration rate, on surgical outcomes following acute type A aortic dissection. We investigated the accuracy of estimated glomerular filtration rate (in ml/min/1.73 m(2)) in predicting in-hospital mortality and postoperative renal replacement therapy in such cases. We reviewed 114 consecutive patients with non-dialysis-dependent renal dysfunction who underwent thoracic aortic surgery for acute type A aortic dissection between 1997 and 2012. Preoperative renal function was categorized as normal (estimated glomerular filtration rate >90; n = 15) or as mild (60-89; n = 39), moderate I (45-59; n = 39), moderate II (30-44; n = 14) or severe (15-29; n = 7) renal dysfunction. In-hospital mortality was 14.9%. Eighteen (15.8%) of 114 patients required renal replacement therapy. A more severe stage stratified by preoperative estimated glomerular filtration rate levels could effectively predict postoperative renal replacement therapy (area under the receiver operating characteristic curve 0.786). The best cut-off value of estimated glomerular filtration rate for predicting postoperative renal replacement therapy was 60 (sensitivity 95%, specificity 59%). On multiple regression analysis, the independent preoperative and intraoperative risk factors for postoperative renal replacement therapy were estimated glomerular filtration rate (P replacement (P replacement therapy (OR, 5.47; P regression analysis. Preoperative estimated glomerular filtration rate can effectively predict the need for renal replacement therapy after surgery for acute type A aortic dissection. However, it is not an effective diagnostic tool to predict in-hospital mortality. The complexity of the characteristics of patients who undergo surgical procedures may make prediction of surgical outcomes difficult. Risk models to predict hospital mortality and morbidities are needed to assist clinicians in

  3. Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

    Science.gov (United States)

    Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R

    2017-10-01

    To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a

  4. [Preoperative, neuropathic component in patients with back pain].

    Science.gov (United States)

    Lee, Y-J; Koch, E M W; Breidebach, J B; Bornemann, R; Wirtz, D C; Pflugmacher, R

    2017-04-01

    The objectification of pain is essential for evaluation, treatment plan and follow-up; therefore, it is necessary to find reliable clinical parameters. The goal of the study was the preoperative screening of a neuropathic component in patients with vertebral compression fracture (WKF), herniated disc (NPP) or spinal cord compression (SKS). Depending on the preoperative condition on admittance, patients were classified into three groups: group 1 WKF, group 2 NPP and group 3 SKS. To characterize the pain we used the painDETECT questionnaire, the Oswestry questionnaire and further questionnaires. All patients were surgically treated according to the diagnosis, e.g. radiofrequency kyphoplasty, nucleotomy or spondylodesis. We evaluated the data from 139 patients (45% WKF, 34% NPP and 21% SKS). There were no differences in preoperative pain intensity (median ordinal scale 0-10) with a mean preoperative score of 7 for all groups. The total score of the painDETECT questionnaire showed significantly higher results in group 2 (median 18) and in group 3 (median 14) than in group 1 (median 9). There was even a significant difference between groups 2 and 3 (p = 0.03). The highest pain intensity was detected in group 1 with a median visual analog scale (VAS) of 71 mm. The total scores in the painDETECT questionnaire and the scores in the Oswestry questionnaire correlated in groups 2 and 3. The painDETECT questionnaire was shown to be a very suitable instrument for evaluating the neuropathic pain component in patients with dorsalgia. This could be very useful in planning further therapy.

  5. 18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Eschmann, Susanne M.; Reimold, Matthias; Bares, Roland; Friedel, Godehard; Paulsen, Frank; Hehr, Thomas; Budach, Wilfried; Langen, Heinz-Jakob

    2007-01-01

    The aim of this study was to evaluate FDG-PET for assessment of therapy response and for prediction of patient outcome after neo-adjuvant radio-chemotherapy (NARCT) of advanced non-small cell lung cancer (NSCLC). Seventy patients with histologically proven stage III NSCLC underwent FDG-PET investigations before and after NARCT. Changes in FDG uptake and PET findings after completion of NARCT were compared with (1) the histology of tumour samples obtained at surgery or repeat mediastinoscopy, and (2) treatment results in terms of achieved operability and long-term survival. The mean average FDG uptake of the primary tumours in the patient group decreased significantly during NARCT (p = 0.004). Sensitivity, specificity and overall accuracy of FDG-PET were 94.5%, 80% and 91%, respectively, for the detection of residual viable primary tumour, and 77%, 68% and 73%, respectively, for the presence of lymph node metastases. A negative PET scan or a reduction in the standardised uptake value (SUV) of more than 80% was the best predictive factor for a favourable outcome of further treatment. Progressive disease according to PET (new tumour manifestations or increasing SUV) was significantly correlated with an unfavourable outcome (p = 0.005). In this subgroup, survival of patients who underwent surgery was not significantly different from survival among those who did not undergo surgery, whereas for the whole patient group, complete tumour resection had a significant influence on outcome. FDG-PET is suitable to assess response to NARCT in patients with stage III NSCLC accurately. It was highly predictive for treatment outcome and patient survival. PET may be helpful in improving restaging after NARCT by allowing reliable assessment of residual tumour viability. (orig.)

  6. Preoperative management in patients with Graves' disease.

    Science.gov (United States)

    Piantanida, Eliana

    2017-10-01

    Graves' disease is the most frequent cause of hyperthyroidism in iodine-sufficient geographical areas and is characterized by the presence in patients' serum of autoantibodies directed against the thyrotropin receptor (TRAb) that cause overproduction and release of thyroid hormones. Clinical presentation results from both hyperthyroidism and underlying autoimmunity. The diagnosis is based on characteristic clinical features and biochemical abnormalities. If serum thyrotropin (TSH) is low, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations should be measured to distinguish between subclinical (with normal circulating thyroid hormones) and overt hyperthyroidism (with increased circulating thyroid hormones). Graves' disease is treated with any of three effective and relatively safe initial treatment options: antithyroid drugs (ATDs), radioactive iodine ablation (RAIU), and surgery. Total thyroidectomy is favored in several clinical situations, such as intolerance, ineffectiveness or recurrence after ATD treatment, radioiodine therapy contraindicated, documented or suspected thyroid malignancy, one or more large thyroid nodules, coexisting moderate-to-severe active Graves' orbitopathy, women planning a pregnancy within 6 months. Whenever surgery is selected as treatment, selection of an expert high-volume thyroid surgeons is fundamental and careful preoperative management is essential to optimize surgical outcomes. Pretreatment with ATDs in order to promptly achieve the euthyroid state is recommended to avoid the risk of precipitating thyroid storm during surgery. For the majority of patients, euthyroidism is achieved after few weeks of ATD treatment. Beta-blockers, such as propranolol, are often added effectively to control hyperthyroid symptoms. Saturated solution of potassium iodide (SSKI) or potassium iodine (Lugol's solution), given for a short period prior to surgery, in order to reduce both thyroid hormone release and thyroid gland

  7. Treatment patterns and prognostic indicators of response to therapy among patients with chronic myeloid leukemia in Australia, Canada, and South Korea.

    Science.gov (United States)

    Whiteley, Jennifer; Iyer, Shrividya; Candrilli, Sean D; Kaye, James A

    2015-02-01

    Given the multiple options for treatment of chronic-phase chronic myeloid leukemia (CML) with tyrosine kinase inhibitors, our objective was to understand treatment patterns in routine practice and prognostic indicators of response. We conducted a retrospective medical record review of 681 patients with CML in Australia, Canada, and South Korea. Eligible patients had a diagnosis of chronic-phase CML, were Philadelphia chromosome and/or BCR-ABL positive, were aged 18 years or older, and had been treated with first-line imatinib therapy between January 2005 and September 2010. Data on patient demographics, medical history (e.g., comorbidities, Sokal score), and treatment characteristics (e.g., time to initiation, therapy duration) were abstracted. Descriptive analyses were stratified by country and therapy line. Prognostic indicators of response to imatinib were evaluated using multivariable logistic regression, adjusting for country, patient demographics, medical history, treatment characteristics, and side effects. Hematologic, cytogenetic, and molecular responses at 3, 6, 12, and 18 months following initiation of each therapy line. Patients' average age was 57 years, and 59% were male. Overall, imatinib was initiated approximately 4 months following CML diagnosis. Complete or major molecular response (C/MMR) at 6 months following imatinib initiation was 54% in Australia, 22% in Canada, and 38% in South Korea. At 18 months, over 60% of patients achieved C/MMR. Approximately 30% of patients discontinued imatinib primarily due to intolerance and lack of response. Among patients who received second-line treatment, dasatinib was used more frequently than nilotinib. Multivariable regression results indicated Sokal score was identified as a prognostic indicator of response to imatinib therapy at several time points. There are several limitations to this study. First, we selected a convenience sample of patients and physicians and therefore results may not be

  8. Cost-utility analysis of dasatinib and nilotinib in patients with chronic myeloid leukemia refractory to first-line treatment with imatinib in Thailand.

    Science.gov (United States)

    Kulpeng, Wantanee; Sompitak, Sumalai; Jootar, Saengsuree; Chansung, Kanchana; Teerawattananon, Yot

    2014-04-01

    Recently, the second-generation tyrosine kinase inhibitors dasatinib and nilotinib have emerged as alternative treatments in patients with chronic myeloid leukemia (CML) who are resistant to or intolerant of imatinib. This article aimed to assess the cost utility and budget impact of using dasatinib or nilotinib, rather than high-dose (800-mg/d) imatinib, in patients with chronic phase (CP) CML who are resistant to standard-dose (400-mg/d) imatinib in Thailand. A Markov simulation model was developed and used to estimate the lifetime costs and outcomes of treating patients aged ≥38 years with CP-CML. The efficacy parameters were synthesized from a systematic review. Utilities using the European Quality of Life-5 Dimensions tool and costs were obtained from the Thai CML population. Costs and outcomes were compared and presented as the incremental cost-effectiveness ratio in 2011 Thai baht (THB) per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty. From a societal perspective, treatment with dasatinib was found to yield more QALYs (2.13) at a lower cost (THB 1,631,331) per person than high-dose imatinib. Nilotinib treatment was also found to be more cost-effective than high-dose imatinib, producing an incremental cost-effectiveness ratio of THB 83,328 per QALY gained. This treatment option also resulted in the highest number of QALYs gained of all of the treatment options. The costs of providing dasatinib, nilotinib, and high-dose imatinib were estimated at THB 5 billion, THB 6 billion, and THB 7 billion, respectively. Treatment with dasatinib or nilotinib is likely to be more cost-effective than treatment with high-dose imatinib in CP-CML patients who do not respond positively to standard-dose imatinib in the Thai context. Dasatinib was found to be more cost-effective than nilotinib. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  9. "Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: An open-label non-randomized, uncontrolled clinical trial"

    DEFF Research Database (Denmark)

    Elmholdt, Tina Rask; Olesen, Anne Braae

    2011-01-01

    Background Nephrogenic systemic fibrosis is a disease affecting the connective tissue of the skin and internal organs in patients with renal failure. No effective treatments are available. Objectives To investigate if the tyrosine kinase inhibitor, imatinib mesylate was effective in patients...... Imatinib mesylate may be an effective drug in the treatment of skin fibrosis in moderate to severe NSF cases, even at reduced doses. We found a positive clinical effect on the skin, but no convincing improvement of the joint mobility. Only few patients could be recruited limiting the interpretation...

  10. 16. PRE-OPERATIVE BLADDER IRRIGATION

    African Journals Online (AJOL)

    Esem

    effectiveness of using preoperative bladder irrigation with 1% povidone iodine in reducing ... consenting patient who presented to the department of surgery for open ..... infections in a tertiary care center in south-western. Nigeria. International ...

  11. Preoperative bowel preparation in children: Polyethylene glycol ...

    African Journals Online (AJOL)

    Preoperative bowel preparation in children: Polyethylene glycol versus normal saline. ... In children, (is this standard of care?: this method is mostly followed) this is usually ... Patients and Methods: Thirty patients, admitted in the Department of ...

  12. Preoperative Alcohol Consumption and Postoperative Complications

    DEFF Research Database (Denmark)

    Eliasen, Marie; Grønkjær, Marie; Skov-Ettrup, Lise Skrubbeltrang

    2013-01-01

    OBJECTIVE:: To systematically review and summarize the evidence of the association between preoperative alcohol consumption and postoperative complications elaborated on complication type. BACKGROUND:: Conclusions in studies on preoperative alcohol consumption and postoperative complications have...... been inconsistent. METHODS:: A systematic review and meta-analysis based on a search in MEDLINE, EMBASE, CINAHL, and PsycINFO citations. Included were original studies of the association between preoperative alcohol consumption and postoperative complications occurring within 30 days of the operation.......30-2.49), prolonged stay at the hospital (RR = 1.24; 95% CI: 1.18-1.31), and admission to intensive care unit (RR = 1.29; 95% CI: 1.03-1.61). Clearly defined high alcohol consumption was associated with increased risk of postoperative mortality (RR = 2.68; 95% CI: 1.50-4.78). Low to moderate preoperative alcohol...

  13. Preoperative preparation of patients with pituitary gland disorders.

    Science.gov (United States)

    Malenković, Vesna; Gvozdenović, Ljiljana; Milaković, Branko; Sabljak, Vera; Ladjević, Nebojsa; Zivaljević, Vladan

    2011-01-01

    This paper presents the most common disorders of pituitary function: acromegaly, hypopituitarism, diabetes insipidus and syndrome similar to diabetes insipidus, in terms of their importance in preoperative preparation of patients. Pituitary function manages almost the entire endocrine system using the negative feedback mechanism that is impaired by these diseases. The cause of acromegaly is a pituitary adenoma, which produces growth hormone in adults. Primary therapy of acromegaly is surgical, with or without associated radiotherapy. If a patient with acromegaly as comorbidity prepares for non-elective neurosurgical operation, then it requires consultation with brain surgeons for possible delays of that operation and primary surgical treatment of pituitary gland. If operative treatment of pituitary gland is carried out, the preoperative preparation (for other surgical interventions) should consider the need for perioperative glucocorticoid supplementation. Panhypopituitarism consequences are different in children and adults and the first step in diagnosis is to assess the function of target organs. Change of electrolytes and water occurs in the case of pituitary lesions in the form of central or nephrogenic diabetes insipidus as a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Preoperative preparation of patients with pituitary dysfunction should be multidisciplinary, whether it is a neurosurgical or some other surgical intervention. The aim is to evaluate the result of insufficient production of pituitary hormones (hypopituitarism), excessive production of adenohypophysis hormones (acromegaly, Cushing's disease and hyperprolactinemia) and the influence of pituitary tumours in surrounding structures (compression syndrome) and to determine the level of perioperative risk. Pharmacological suppressive therapy of the hyperfunctional pituitary disorders can have significant interactions with drugs used in the perioperative period.

  14. Short-term Preoperative Octreotide for Thyrotropin-secreting Pituitary Adenoma

    Directory of Open Access Journals (Sweden)

    Hong-Juan Fang

    2017-01-01

    Conclusions: OCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.

  15. Survival of gastrointestinal stromal tumor patients in the imatinib era: life raft group observational registry

    Directory of Open Access Journals (Sweden)

    Call Jerry

    2012-03-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST, one of the most common mesenchymal tumors of the gastrointestinal tract, prior to routine immunohistochemical staining and the introduction of tyrosine kinase inhibitors, were often mistaken for neoplasms of smooth muscle origin such as leiomyomas, leiomyosarcomas or leiomyoblastomas. Since the advent of imatinib, GIST has been further delineated into adult- (KIT or PDGFRα mutations and pediatric- (typified by wild-type GIST/succinate dehydrogenase deficiencies types. Using varying gender ratios at age of diagnosis we sought to elucidate prognostic factors for each sub-type and their impact on overall survival. Methods This is a long-term retrospective analysis of a large observational study of an international open cohort of patients from a GIST research and patient advocacy's lifetime registry. Demographic and disease-specific data were voluntarily supplied by its members from May 2000-October 2010; the primary outcome was overall survival. Associations between survival and prognostic factors were evaluated by univariate Cox proportional hazard analyses, with backward selection at P Results Inflections in gender ratios by age at diagnosis in years delineated two distinct groups: above and below age 35 at diagnosis. Closer analysis confirmed the above 35 age group as previously reported for adult-type GIST, typified by mixed primary tumor sites and gender, KIT or PDGFRα mutations, and shorter survival times. The pediatric group ( Conclusions Pediatric- and adult-type GIST have been previously characterized in clinical settings and these observations confirm significant prognostic factors for each from a diverse real-world cohort. Additionally, these findings suggest that extra diligence be taken with "young adults" (aged 18-35 at diagnosis as pediatric-type GIST may present well beyond adolescence, particularly as these distinct sub-types have different causes, and consequently

  16. SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation

    International Nuclear Information System (INIS)

    Giallongo, Cesarina; Palumbo, Giuseppe A; Di Raimondo, Francesco; La Cava, Piera; Tibullo, Daniele; Barbagallo, Ignazio; Parrinello, Nunziatina; Cupri, Alessandra; Stagno, Fabio; Consoli, Carla; Chiarenza, Annalisa

    2013-01-01

    SPARC is a matricellular glycoprotein with growth-inhibitory and antiangiogenic activity in some cell types. The study of this protein in hematopoietic malignancies led to conflicting reports about its role as a tumor suppressor or promoter, depending on its different functions in the tumor microenvironment. In this study we investigated the variations in SPARC production by peripheral blood cells from chronic myeloid leukemia (CML) patients at diagnosis and after treatment and we identified the subpopulation of cells that are the prevalent source of SPARC. We evaluated SPARC expression using real-time PCR and western blotting. SPARC serum levels were detected by ELISA assay. Finally we analyzed the interaction between exogenous SPARC and imatinib (IM), in vitro, using ATP-lite and cell cycle analysis. Our study shows that the CML cells of patients at diagnosis have a low mRNA and protein expression of SPARC. Low serum levels of this protein are also recorded in CML patients at diagnosis. However, after IM treatment we observed an increase of SPARC mRNA, protein, and serum level in the peripheral blood of these patients that had already started at 3 months and was maintained for at least the 18 months of observation. This SPARC increase was predominantly due to monocyte production. In addition, exogenous SPARC protein reduced the growth of K562 cell line and synergized in vitro with IM by inhibiting cell cycle progression from G1 to S phase. Our results suggest that low endogenous SPARC expression is a constant feature of BCR/ABL positive cells and that IM treatment induces SPARC overproduction by normal cells. This exogenous SPARC may inhibit CML cell proliferation and may synergize with IM activity against CML

  17. SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation

    Directory of Open Access Journals (Sweden)

    Giallongo Cesarina

    2013-02-01

    Full Text Available Abstract Background SPARC is a matricellular glycoprotein with growth-inhibitory and antiangiogenic activity in some cell types. The study of this protein in hematopoietic malignancies led to conflicting reports about its role as a tumor suppressor or promoter, depending on its different functions in the tumor microenvironment. In this study we investigated the variations in SPARC production by peripheral blood cells from chronic myeloid leukemia (CML patients at diagnosis and after treatment and we identified the subpopulation of cells that are the prevalent source of SPARC. Methods We evaluated SPARC expression using real-time PCR and western blotting. SPARC serum levels were detected by ELISA assay. Finally we analyzed the interaction between exogenous SPARC and imatinib (IM, in vitro, using ATP-lite and cell cycle analysis. Results Our study shows that the CML cells of patients at diagnosis have a low mRNA and protein expression of SPARC. Low serum levels of this protein are also recorded in CML patients at diagnosis. However, after IM treatment we observed an increase of SPARC mRNA, protein, and serum level in the peripheral blood of these patients that had already started at 3 months and was maintained for at least the 18 months of observation. This SPARC increase was predominantly due to monocyte production. In addition, exogenous SPARC protein reduced the growth of K562 cell line and synergized in vitro with IM by inhibiting cell cycle progression from G1 to S phase. Conclusion Our results suggest that low endogenous SPARC expression is a constant feature of BCR/ABL positive cells and that IM treatment induces SPARC overproduction by normal cells. This exogenous SPARC may inhibit CML cell proliferation and may synergize with IM activity against CML.

  18. In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow

    Directory of Open Access Journals (Sweden)

    P.B. Soares

    2013-01-01

    Full Text Available Imatinib mesylate (IM is used to treat chronic myeloid leukemia (CML because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM. The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM, using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25 µM reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5 µM. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells increased. At higher concentrations (15 µM, the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control. Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases in groups treated with 5-15 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved.

  19. Rapid Determination of Imatinib in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jeong Soo; Cho, Eun Gi; Huh, Wooseong; Ko, Jaewook; Jung, Jin Ah; Lee, Sooyoun [Samsung Medical Center, Seoul (Korea, Republic of)

    2013-08-15

    A simple, fast and robust analytical method was developed to determine imatinib in human plasma using liquid chromatography-tandem mass spectrometry with electrospray ionization in the positive ion mode. Imatinib and labeled internal standard were extracted from plasma with a simple protein precipitation. The chromatographic separation was performed using an isocratic elution of mobile phase involving 5.0 mM ammonium formate in water -5.0 mM ammonium formate in methanol (30:70, v/v) over 3.0 min on reversed-stationary phase. The detection was performed using a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. The developed method was validated with lower limit of quantification of 10 ng/mL. The calibration curve was linear over 10-2000 ng/mL (R{sup 2} > 0.99). The method validation parameters met the acceptance criteria. The spiked samples and standard solutions were stable under conditions for storage and handling. The reliable method was successfully applied to real sample analyses and thus a pharmacokinetic study in 27 healthy Korean male volunteers.

  20. The impact assessment of anticancer drug imatinib on the feeding behavior of rotifers with an integrated perspective: Exposure, post-exposure and re-exposure.

    Science.gov (United States)

    Yan, Zhengyu; Yan, Kun; He, Xingliang; Liu, Yanhua; Zhang, Jie; Lopez Torres, Oscar; Guo, Ruixin; Chen, Jianqiu

    2017-10-01

    The anticancer drugs are getting increasing attention as an emerging contaminant in the aquatic environments. In the present study, feeding behavior of the rotifer Brachionus calyciflorus under the impact of anticancer drug imatinib was evaluated. Traditional toxicological studies usually focus on dose-effect relationship at a given exposure time, while ignore the possible impact after the exposure. Thus, how the impact varied in the post-exposure and re-exposure was also considered in the present study. The feeding depression of the rotifers was attributed to the increased concentration of imatinib. Although the filtration and ingestion rate of the rotifers recovered to a certain extent after the exposure, the significant feeding inhibition still persisted even if the exposure was ended. In the re-exposure period, the feeding behavior was less depressed than those of the exposure period, which implied that rotifers might develop a tolerance to the same toxics. The activities of acetylcholine esterase (AchE) and the levels of reactive oxygen species (ROS) in rotifers were also detected. Imatinib inhibited the activities of AchE in the exposure and re-exposure while ROS levels increased significantly in the re-exposure period. Our present study provided an integrated assessment the potential environmental risks of imatinib at a new perspective. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Quantification of imatinib in human serum: validation of a high-performance liquid chromatography-mass spectrometry method for therapeutic drug monitoring and pharmacokinetic assays.

    Science.gov (United States)

    Rezende, Vinicius Marcondes; Rivellis, Ariane; Novaes, Mafalda Megumi Yoshinaga; de Alencar Fisher Chamone, Dalton; Bendit, Israel

    2013-01-01

    Imatinib mesylate has been a breakthrough treatment for chronic myeloid leukemia. It has become the ideal tyrosine kinase inhibitor and the standard treatment for chronic-phase leukemia. Striking results have recently been reported, but intolerance to imatinib and noncompliance with treatment remain to be solved. Molecular monitoring by quantitative real-time polymerase chain reaction is the gold standard for monitoring patients, and imatinib blood levels have also become an important tool for monitoring. A fast and cheap method was developed and validated using high-performance liquid chromatography-mass spectrometry for quantification of imatinib in human serum and tamsulosin as the internal standard. Remarkable advantages of the method includes use of serum instead of plasma, less time spent on processing and analysis, simpler procedures, and requiring reduced amounts of biological material, solvents, and reagents. Stability of the analyte was also studied. This research also intended to drive the validation scheme in clinical centers. The me