Radiolytic oxidation of tamoxifen using the free radicals .OH and (or) HO2

International Nuclear Information System (INIS)

Leguene, C.; Clavere, P.; Jore, D.; Gardes-Albert, M.

2001-01-01

Tamoxifen is the most widely used antiestrogen in the treatment of breast cancer. In this work, we have studied its antioxidant properties. We have investigated the ability of tamoxifen to scavenge, in vitro, . OH and (or) HO 2 . free radicals that are produced by water radiolysis. Aqueous solutions of tamoxifen of concentrations ranging between 10 -5 and 2.5 x 10 -5 M have been irradiated (γ 137 Cs) in aerated acidic medium (H 3 PO 4 10 -3 M or HCOOH 10 -1 M). The results show that tamoxifen reacts quantitatively with . OH free radicals but does not react with HO 2 . free radicals under our experimental conditions. (author)

Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial

DEFF Research Database (Denmark)

Regan, M.M.; Lykkesfeldt, A.E.; Dell'Orto, P.

2008-01-01

Background The Breast International Group (BIG) 1-98 trial (a randomised double-blind phase III trial) has shown that letrozole significantly improves disease-free survival (DFS) compared with tamoxifen in postmenopausal women with endocrine-responsive early breast cancer. Our aim was to establish...... whether the benefit of letrozole versus tamoxifen differs according to the ERBB2 status of tumours. Methods The BIG 1-98 trial consists of four treatment groups that compare 5 years of monotherapy with letrozole or tamoxifen, and sequential administration of one drug for 2 years followed by the other drug...... for 3 years. Our study includes data from the 4922 patients randomly assigned to the two monotherapy treatment groups (letrozole or tamoxifen for 5 years; 51 months median follow-up [range

A pooled analysis of CYP2D6 genotype in breast cancer prevention trials of low-dose tamoxifen.

Science.gov (United States)

Johansson, Harriet; Gandini, Sara; Serrano, Davide; Gjerde, Jennifer; Lattanzi, Monia; Macis, Debora; Guerrieri-Gonzaga, Aliana; Aristarco, Valentina; Mellgren, Gunnar; Lien, Ernst; DeCensi, Andrea; Bonanni, Bernardo

2016-08-01

Decreased CYP2D6 activity is associated with lower levels of active tamoxifen metabolites. We examined the impact of CYP2D6 genotype on tamoxifen pharmacokinetics, biomarker activity, and efficacy in a pooled analysis of low-dose tamoxifen. Four randomized breast cancer prevention trials of very-low-dose (1 mg/day, n = 52 or 10 mg/week, n = 152) or low-dose tamoxifen (5 mg/day, n = 171) were pooled. DNA from 367 subjects was genotyped for CYP2D6 alleles associated with absent (PM allele: *3, *4, *5, *6, *7, *8, *12, and *14), reduced (IM allele: *9, *10, *17, *29, *41), normal (EM allele), or increased (UM: *XN) enzyme activity. Associations of tamoxifen, metabolites, activity biomarkers, and event-free survival with rapid (UM/EM, UM/IM, EM/EM, EM/IM, or EM/PM alleles) versus slow metabolizers (PM/IM or PM/PM) were investigated through random effects models, with 'study' as the random factor, and Cox regression models, adjusting for confounders. Rapid metabolizers had higher endoxifen levels than slow metabolizers: 15.3 versus 12.2 ng/mL (P = 0.018) with 5 mg/day, and 3.8 versus 2.8 ng/mL (P = 0.004) with 1 mg/day or 10 mg/week tamoxifen. The IGF-I decrease correlated with endoxifen (P = 0.002) and 4-hydroxytamoxifen levels, demonstrating steeper decreases at higher metabolite levels (P = 0.001). After a median follow-up of 12 years, rapid metabolizers with prior history of breast neoplasms allocated to tamoxifen 5 mg/day had a 60 % reduction of risk of recurrences (HR = 0.40, 95 % CI: 0.16-0.99) compared to slow metabolizers. CYP2D6 genotype may have an impact on tamoxifen efficacy at low doses. Trials investigating tamoxifen dose adjustments based on the woman's hormonal context and CYP2D6 genotype are warranted.

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor-Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14.

Science.gov (United States)

Wolmark, Norman; Mamounas, Eleftherios P; Baehner, Frederick L; Butler, Steven M; Tang, Gong; Jamshidian, Farid; Sing, Amy P; Shak, Steven; Paik, Soonmyung

2016-07-10

We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups. RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low ( 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. © 2016 by American Society of Clinical Oncology.

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor–Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14

Science.gov (United States)

Wolmark, Norman; Baehner, Frederick L.; Butler, Steven M.; Tang, Gong; Jamshidian, Farid; Sing, Amy P.; Shak, Steven; Paik, Soonmyung

2016-01-01

Purpose We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1–expressing groups. Patients and Methods RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) –positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Results Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low ( 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). Conclusion For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. PMID:27217450

Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial

DEFF Research Database (Denmark)

Crivellari, D.; Sun, Z.; Coates, A.S.

2008-01-01

PURPOSE: To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial. METHODS: This report includes the 4,922 patients allocated to 5 years...... of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were...... had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy Udgivelsesdato: 2008/4/20...

Tamoxifen-loaded polymeric micelles: preparation, physico-chemical characterization and in vitro evaluation studies.

Science.gov (United States)

Cavallaro, Gennara; Maniscalco, Laura; Licciardi, Mariano; Giammona, Gaetano

2004-11-20

Several samples of polymeric micelles, formed by amphiphilic derivatives of PHEA, obtained by grafting into polymeric backbone of PEGs and/or hexadecylamine groups (PHEA-PEG-C(16) and PHEA-C(16)) and containing different amount of Tamoxifen, were prepared. All Tamoxifen-loaded polymeric micelles showed to increase drug water solubility. TEM studies provided evidence of the formation of supramolecular core/shell architectures containing drug, in the nanoscopic range and with spherical shape. Samples with different amount of encapsulated Tamoxifen were subjected to in vitro cytotoxic studies in order to evaluate the effect of Tamoxifen micellization on cell growth inhibition. All samples of Tamoxifen-loaded polymeric micelles showed a significantly higher antiproliferative activity in comparison with free drug, probably attributable to fluidification of cellular membranes, caused by amphiphilic copolymers, that allows a higher penetration of the drug into tumoral cells. To gain preliminary information about the potential use of prepared micelles as Tamoxifen drug delivery systems, studies evaluating drug release ability of micelle systems in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma were carried out. These studies, performed evaluating the amount of Tamoxifen that remains in solution as a function of time, showed that at pH 7.4, as well as in plasma, PHEA-C(16) polymeric micelles were able to release lower drug amounts than PHEA-PEG(5000)-C(16) ones, while at pH 5.5, the behavior difference between two kind of micelles was less pronounced.

Antiarrhythmic effect of tamoxifen on the vulnerability induced by hyperthyroidism to heart ischemia/reperfusion damage.

Science.gov (United States)

Pavón, Natalia; Hernández-Esquivel, Luz; Buelna-Chontal, Mabel; Chávez, Edmundo

2014-09-01

Hyperthyroidism, known to have deleterious effects on heart function, and is associated with an enhanced metabolic state, implying an increased production of reactive oxygen species. Tamoxifen is a selective antagonist of estrogen receptors. These receptors make the hyperthyroid heart more susceptible to ischemia/reperfusion. Tamoxifen is also well-known as an antioxidant. The aim of the present study was to explore the possible protective effect of tamoxifen on heart function in hyperthyroid rats. Rats were injected daily with 3,5,3'-triiodothyronine at 2mg/kg body weight during 5 days to induce hyperthyroidism. One group was treated with 10mg/kg tamoxifen and another was not. The protective effect of the drug on heart rhythm was analyzed after 5 min of coronary occlusion followed by 5 min reperfusion. In hyperthyroid rats not treated with tamoxifen, ECG tracings showed post-reperfusion arrhythmias, and heart mitochondria isolated from the ventricular free wall lost the ability to accumulate and retain matrix Ca(2+) and to form a high electric gradient. Both of these adverse effects were avoided with tamoxifen treatment. Hyperthyroidism-induced oxidative stress caused inhibition of cis-aconitase and disruption of mitochondrial DNA, effects which were also avoided by tamoxifen treatment. The current results support the idea that tamoxifen inhibits the hypersensitivity of hyperthyroid rat myocardium to reperfusion damage, probably because its antioxidant activity inhibits the mitochondrial permeability transition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Radiolytic oxidation of tamoxifen using the free radicals {sup .}OH and (or) HO{sub 2}{sup .}; Oxydation radiolytique du tamoxifene par les radicaux libres {sup .}OH et (ou) HO{sub 2}{sup .}

Energy Technology Data Exchange (ETDEWEB)

Leguene, C. [Lab. de Chimie-Physique, Centre national de la recherche scientifique, CNRS, Univ. Rene Descartes, Paris (France); Clavere, P. [Service de Radiotherapie et d' Oncologie, Centre hospitalier universitaire, CHU, Dupuytren, Limoges (France); Jore, D.; Gardes-Albert, M. [Lab. de Chimie-Physique, Centre national de la recherche scientifique, CNRS, Univ. Rene Descartes, Paris (France)

2001-02-01

Tamoxifen is the most widely used antiestrogen in the treatment of breast cancer. In this work, we have studied its antioxidant properties. We have investigated the ability of tamoxifen to scavenge, in vitro, {sup .}OH and (or) HO{sub 2}{sup .} free radicals that are produced by water radiolysis. Aqueous solutions of tamoxifen of concentrations ranging between 10{sup -5} and 2.5 x 10{sup -5} M have been irradiated ({gamma} {sup 137}Cs) in aerated acidic medium (H{sub 3}PO{sub 4} 10{sup -3} M or HCOOH 10{sup -1} M). The results show that tamoxifen reacts quantitatively with {sup .}OH free radicals but does not react with HO{sub 2}{sup .} free radicals under our experimental conditions. (author)

Topical lidocaine patch 5% for acute postoperative pain control.

LENUS (Irish Health Repository)

Gilhooly, D

2011-02-01

A 39-year-old para 3 woman presented for elective caesarean section (lower segment caesarean section (LSCS)) for breech presentation. The patient had a strong history of atopy and anaphylaxis to paracetamol, codeine, penicillin and latex. The patient was asthmatic, triggered by aspirin. Epidural anaesthesia was unsuccessful and LSCS was carried out under spinal anaesthesia. Postoperatively the patient was unwilling to take analgesic medication due to fear of an allergic reaction. Three 5% lidocaine patches were applied to the wound for postoperative analgesia. This reduced the patient\\'s visual analogue scale pain score from 10\\/10 to 5\\/10 at rest and 10\\/10 to 7\\/10 with movement. Transcutaneous electrical nerve stimulation was added and this improved associated back pain, reducing the pain further to 2\\/10. This is the first description of lignocaine patch 5% for postoperative LSCS pain. It is suggested that this method of delivery of local anaesthetic, which is easy to apply and has minimal side effects, should be considered not as a sole agent but as part of a multimodal technique to address postoperative LSCS pain.

Tamoxifen for women at high risk of breast cancer

OpenAIRE

Nazarali, Safia A; Narod, Steven A

2014-01-01

Safia A Nazarali, Steven A Narod Women's College Research Institute, Women's College Hospital, and The University of Toronto, Toronto, Ontario, Canada Abstract: Tamoxifen has been used as a treatment for women who have been diagnosed with breast cancer for roughly four decades and has been approved as chemoprevention for over ten years. Although tamoxifen has been proven to be beneficial in preventing breast cancer in high-risk women, its use has not been widely embraced. To ...

Mammographic density changes following discontinuation of tamoxifen in premenopausal women with oestrogen receptor-positive breast cancer.

Science.gov (United States)

Kim, Won Hwa; Cho, Nariya; Kim, Young-Seon; Yi, Ann

2018-04-06

To evaluate the changes in mammographic density after tamoxifen discontinuation in premenopausal women with oestrogen receptor-positive breast cancers and the underlying factors METHODS: A total of 213 consecutive premenopausal women with breast cancer who received tamoxifen treatment after curative surgery and underwent three mammograms (baseline, after tamoxifen treatment, after tamoxifen discontinuation) were included. Changes in mammographic density after tamoxifen discontinuation were assessed qualitatively (decrease, no change, or increase) by two readers and measured quantitatively by semi-automated software. The association between % density change and clinicopathological factors was evaluated using univariate and multivariate regression analyses. After tamoxifen discontinuation, a mammographic density increase was observed in 31.9% (68/213, reader 1) to 22.1% (47/213, reader 2) by qualitative assessment, with a mean density increase of 1.8% by quantitative assessment compared to density before tamoxifen discontinuation. In multivariate analysis, younger age (≤ 39 years) and greater % density decline after tamoxifen treatment (≥ 17.0%) were independent factors associated with density change after tamoxifen discontinuation (p density change with a mean density increase of 1.8%, which was associated with younger age and greater density change after tamoxifen treatment. • Increased mammographic density after tamoxifen discontinuation can occur in premenopausal women. • Mean density increase after tamoxifen discontinuation was 1.8%. • Density increase is associated with age and density decrease after tamoxifen.

Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells.

Science.gov (United States)

Ambrosio, Maria Rosaria; D'Esposito, Vittoria; Costa, Valerio; Liguoro, Domenico; Collina, Francesca; Cantile, Monica; Prevete, Nella; Passaro, Carmela; Mosca, Giusy; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Ciccodicola, Alfredo; Formisano, Pietro

2017-12-12

Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.

Genotoxic, epigenetic, and transcriptomic effects of tamoxifen in mouse liver

International Nuclear Information System (INIS)

Conti, Aline de; Tryndyak, Volodymyr; Churchwell, Mona I.; Melnyk, Stepan; Latendresse, John R.; Muskhelishvili, Levan; Beland, Frederick A.; Pogribny, Igor P.

2014-01-01

Highlights: • Treatment of female mice with tamoxifen caused genotoxic changes in the livers. • Tamoxifen treatment did not affect the hepatic epigenome. • Tamoxifen caused over-expression of hepatic Lcn13 and Pparγ genes. • Mice are resistant to tamoxifen-induced liver carcinogenesis and fatty liver injury. - Abstract: Tamoxifen is a non-steroidal anti-estrogenic drug widely used for the treatment and prevention of breast cancer in women; however, there is evidence that tamoxifen is hepatocarcinogenic in rats, but not in mice. Additionally, it has been reported that tamoxifen may cause non-alcoholic fatty liver disease (NAFLD) in humans and experimental animals. The goals of the present study were to (i) investigate the mechanisms of the resistance of mice to tamoxifen-induced hepatocarcinogenesis, and (ii) clarify effects of tamoxifen on NAFLD-associated liver injury. Feeding female WSB/EiJ mice a 420 p.p.m. tamoxifen-containing diet for 12 weeks resulted in an accumulation of tamoxifen-DNA adducts, (E)-α-(deoxyguanosin-N 2 -yl)-tamoxifen (dG-TAM) and (E)-α-(deoxyguanosin-N 2 -yl)-N-desmethyltamoxifen (dG-DesMeTAM), in the livers. The levels of hepatic dG-TAM and dG-DesMeTAM DNA adducts in tamoxifen-treated mice were 578 and 340 adducts/108 nucleotides, respectively, while the extent of global DNA and repetitive elements methylation and histone modifications did not differ from the values in control mice. Additionally, there was no biochemical or histopathological evidence of NAFLD-associated liver injury in mice treated with tamoxifen. A transcriptomic analysis of differentially expressed genes demonstrated that tamoxifen caused predominantly down-regulation of hepatic lipid metabolism genes accompanied by a distinct over-expression of the lipocalin 13 (Lcn13) and peroxisome proliferator receptor gamma (Pparγ), which may prevent the development of NAFLD. The results of the present study demonstrate that the resistance of mice to tamoxifen

The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

International Nuclear Information System (INIS)

Kim, Hyun-Ah; Ahn, Sei Hyun; Nam, Seok Jin; Park, Seho; Ro, Jungsil

2016-01-01

Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy

Mullerian adenosarcoma of the uterus associated with tamoxifen treatment for breast cancer

Directory of Open Access Journals (Sweden)

Yasin Ceylan

2015-12-01

Full Text Available Mullerian adenosarcoma following tamoxifen therapy is a rare condition. Our aim was to report the youngest patient in the literature with uterine mullerian adenosarcoma who was undergoing tamoxifen therapy for breast cancer. A premenopausal woman aged 38 years who was undergoing tamoxifen therapy for breast cancer, was admitted with symptoms of lower abdominal pain and irregular vaginal bleeding and malodorous vaginal discharge that had continued for at least 6 months. A pelvic examination revealed a large and malodorous polypoid mass protruding through the cervix and an enlarged uterus. A biopsy from the protruding polypoid mass was reported as a large area of necrosis with neoplastic mesenchymal cells. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oopherectomy, pelvic-paraaortic lymph node dissection, and omentectomie. The histologic diagnosis was Mullerian adenosarcoma. As a result, she was discharged to the oncology department. The woman is alive and her chemoradiotherapy treatment is ongoing. The role of tamoxifen therapy in the development of endometrial neoplasms remains unclear, but all cases of endometrial thickening and vaginal bleeding must be investigated for Mullerian adenosarcoma in tamoxifen users.

Tumorigenic Effects of Tamoxifen on the Female Genital Tract

Directory of Open Access Journals (Sweden)

Kaei Nasu M.D., Ph.D.

2008-01-01

Full Text Available Tamoxifen is widely used for endocrine treatment and breast cancer prevention. It acts as both an estrogen antagonist in breast tissue and an estrogen agonist in the female lower genital tract. Tamoxifen causes severe gynecologic side effects, such as endometrial cancer. This review focuses on the effects of prolonged tamoxifen treatment on the human female genital tract and considers its tumorigenicity in the gynecologic organs through clinical data analysis. Tamoxifen is associated with an increased incidence of benign endometrial lesions such as polyps and hyperplasia and a two- to four-fold increased risk of endometrial cancer in postmenopausal patients. Moreover, the incidence of functional ovarian cysts is significantly high in premenopausal tamoxifen users. To prevent tamoxifen from having severe side effects in gynecologic organs, frequent gynecological examination should be performed for both premenopausal and postmenopausal patients with breast cancer who are treated with this drug.

Adenosarcoma of the uterus following tamoxifen treatment for breast cancer

NARCIS (Netherlands)

Mourits, MJE; Hollema, H; Willemse, PHB; De Vries, EGE; Aalders, JG; Van der Zee, AGJ

1998-01-01

A 71-year-old patient developed an uterine adenosarcoma two months after two years of tamoxifen adjuvant treatment for early breast cancer. After curettage for postmenopausal bleeding, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic

The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

Science.gov (United States)

Dorchies, Olivier M; Reutenauer-Patte, Julie; Dahmane, Elyes; Ismail, Heham M; Petermann, Olivier; Patthey- Vuadens, Ophélie; Comyn, Sophie A; Gayi, Elinam; Piacenza, Tony; Handa, Robert J; Décosterd, Laurent A; Ruegg, Urs T

2013-02-01

Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.

Tamoxifen in the Mouse Brain: Implications for Fate-Mapping Studies Using the Tamoxifen-Inducible Cre-loxP System

Czech Academy of Sciences Publication Activity Database

Valný, Martin; Honsa, Pavel; Kirdajová, Denisa; Kameník, Zdeněk; Anděrová, Miroslava

2016-01-01

Roč. 10, ost (2016), s. 243 ISSN 1662-5102 R&D Projects: GA ČR(CZ) GA16-10214S; GA ČR(CZ) GA15-02760S Institutional support: RVO:68378041 ; RVO:61388971 Keywords : tamoxifen * brain metabolism * fate-mapping Subject RIV: FH - Neurology; EE - Microbiology, Virology (MBU-M) Impact factor: 4.555, year: 2016

The formation of estrogen-like tamoxifen metabolites and their influence on enzyme activity and gene expression of ADME genes.

Science.gov (United States)

Johänning, Janina; Kröner, Patrick; Thomas, Maria; Zanger, Ulrich M; Nörenberg, Astrid; Eichelbaum, Michel; Schwab, Matthias; Brauch, Hiltrud; Schroth, Werner; Mürdter, Thomas E

2018-03-01

Tamoxifen, a standard therapy for breast cancer, is metabolized to compounds with anti-estrogenic as well as estrogen-like action at the estrogen receptor. Little is known about the formation of estrogen-like metabolites and their biological impact. Thus, we characterized the estrogen-like metabolites tamoxifen bisphenol and metabolite E for their metabolic pathway and their influence on cytochrome P450 activity and ADME gene expression. The formation of tamoxifen bisphenol and metabolite E was studied in human liver microsomes and Supersomes™. Cellular metabolism and impact on CYP enzymes was analyzed in upcyte® hepatocytes. The influence of 5 µM of tamoxifen, anti-estrogenic and estrogen-like metabolites on CYP activity was measured by HPLC MS/MS and on ADME gene expression using RT-PCR analyses. Metabolite E was formed from tamoxifen by CYP2C19, 3A and 1A2 and from desmethyltamoxifen by CYP2D6, 1A2 and 3A. Tamoxifen bisphenol was mainly formed from (E)- and (Z)-metabolite E by CYP2B6 and CYP2C19, respectively. Regarding phase II metabolism, UGT2B7, 1A8 and 1A3 showed highest activity in glucuronidation of tamoxifen bisphenol and metabolite E. Anti-estrogenic metabolites (Z)-4-hydroxytamoxifen, (Z)-endoxifen and (Z)-norendoxifen inhibited the activity of CYP2C enzymes while tamoxifen bisphenol consistently induced CYPs similar to rifampicin and phenobarbital. On the transcript level, highest induction up to 5.6-fold was observed for CYP3A4 by tamoxifen, (Z)-4-hydroxytamoxifen, tamoxifen bisphenol and (E)-metabolite E. Estrogen-like tamoxifen metabolites are formed in CYP-dependent reactions and are further metabolized by glucuronidation. The induction of CYP activity by tamoxifen bisphenol and the inhibition of CYP2C enzymes by anti-estrogenic metabolites may lead to drug-drug-interactions.

Tamoxifen treatment of bleeding irregularities associated with Norplant use.

Science.gov (United States)

Abdel-Aleem, Hany; Shaaban, Omar M; Amin, Ahmed F; Abdel-Aleem, Aly M

2005-12-01

To evaluate the possible role of tamoxifen (selective estrogen receptor modulators, SERM) in treating bleeding irregularities associated with Norplant contraceptive use. Randomized clinical trial including 100 Norplant users complaining of vaginal bleeding irregularities. The trial was conducted in the Family Planning Clinic of Assiut University Hospital. Women were assigned at random to receive tamoxifen tablets (10 mg) twice daily for 10 days or similar placebo. Women were followed-up for 3 months. The end points were percentage of women who stopped bleeding during treatment, bleeding/spotting days during the period of follow-up, effect of treatment on their lifestyle, and side effects and discontinuation of contraception. There was good compliance with treatment. At the end of treatment, a significantly higher percentage of tamoxifen users stopped bleeding in comparison to the control group (88% vs. 68%, respectively; p=.016). Women who used tamoxifen had significantly less bleeding and/or spotting days than women who used placebo, during the first and second months. During the third month, there were no significant differences between the two groups. Women who used tamoxifen reported improvement in performing household activities, religious duties and in sexual life, during the first 2 months. In the third month, there were no differences between the two groups. There were no significant differences between tamoxifen and placebo groups in reporting side effects. In the group who used tamoxifen, two women discontinued Norplant use because of bleeding vs. nine women in the placebo group. Tamoxifen use at a dose of 10 mg twice daily orally, for 10 days, has a beneficial effect on vaginal bleeding associated with Norplant use. In addition, the bleeding pattern was better in women who used tamoxifen for the following 2 months after treatment. However, these results have to be confirmed in a larger trial before advocating this line of treatment.

Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.

Science.gov (United States)

Choi, Hee-Joo; Joo, Hyeong-Seok; Won, Hee-Young; Min, Kyueng-Whan; Kim, Hyung-Yong; Son, Taekwon; Oh, Young-Ha; Lee, Jeong-Yeon; Kong, Gu

2018-04-01

Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase assay were performed to identify the tamoxifen resistance mechanism by RBP2. All statistical tests were two-sided. RBP2 was associated with poor prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore, RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity, whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9] mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P < .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors and regulated several tamoxifen resistance-associated genes, including NRIP1, CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R) activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT activation via demethylase activity-independent ErbB protein stabilization. Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2-mediated tamoxifen

Detection of tamoxifen metabolites by GC-MSD.

Science.gov (United States)

Báez, H; Camargo, C; Osorio, H; Umpiérrez, F

2004-01-01

Tamoxifen is an antiestrogen used in the adjuvant endocrine therapy of early breast cancer and malignant breast disorders. It is also used in women with anovulatory infertility caused by its stimulating effect on the secretion of the pituitary gonadotrophic hormones. In males it could increase the endogenous production of androgens. Because of these properties tamoxifen may be misused in some sports to treat the androgens suppression caused by the extensive abuse of anabolic androgenic steroids. A method for identification and confirmation of tamoxifen metabolites is described. Hydroxymetoxytamoxifen is detected in urine by gas chromatography and mass spectrometry in a selective ion monitoring method followed by the routine postrun in the screening of anabolic steroids. Once the hydroxymetoxytamoxifen is detected, confirmation of reported metabolites could be performed with a 5973 mass selective detector in the scan mode after solid-phase extraction by cationic exchange. This study also reports an excretion profile for a single dose of tamoxifen equivalent to 40 mg administrated orally to two males volunteers.

[Effect of the estrogen antagonist tamoxifen in the treatment of advanced mastocarcinoma (author's transl)].

Science.gov (United States)

Szepesi, T; Kärcher, K H

1977-12-01

Today the endocrin therapy of the advanced mastocarcinoma is in common use. Besides the already known therapy by estrogens, androgens, gestagens, and steroids, Tamoxifen, and estrogen antagonist, is a very promising therapeutic drug. In the presented study, Tamoxifen was submitted to a critical clinical control during a period of one year from 1st October 1975 until 1st October 1976. After a three months' treatment, a rate of 41% of objective remissions could be obtained. The criteria of success were estimated according to the scheme of Karnofsky. The average remission time is 5,5 months. By a determination of the estrogen receptors it would be possible to realize a therapeutic selection and to achieve a higher remission rate. The authors made an interesting observation, i.e. a probably immuno-stimulating effect which, however, still has to be submitted to further examinations. The side effects are described in detail and the indications are established. Its is astonishing that the subjective ameliorations, i.e. cessation of pains in case of generalized formation of metastases in the bones are much more frequent than the objective remissions. We came to the conclusion that the treatment by Tamoxifen is a valuable alternative in the therapy of the mastocarcinoma, above all in the postmenopausal period if the disease is advanced and incurable.

Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

International Nuclear Information System (INIS)

Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Muskhelishvili, Levan; Rodriguez-Juarez, Rocio; Kovalchuk, Olga; Han Tao; Fuscoe, James C.; Ross, Sharon A.; Beland, Frederick A.

2007-01-01

Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G 1 to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen

Tamoxifen treatment for pubertal gynecomastia in two siblings with partial androgen insensitivity syndrome.

Science.gov (United States)

Saito, Reiko; Yamamoto, Yukiyo; Goto, Motohide; Araki, Shunsuke; Kubo, Kazuyasu; Kawagoe, Rinko; Kawada, Yasusada; Kusuhara, Koichi; Igarashi, Maki; Fukami, Maki

2014-01-01

Although tamoxifen has been shown to be fairly safe and effective for idiopathic pubertal gynecomastia, it remains unknown whether it is also beneficial for gynecomastia associated with endocrine disorders. Here, we report the effect of tamoxifen on pubertal gynecomastia in 2 siblings with partial androgen insensitivity syndrome (PAIS). Cases 1 and 2 presented with persistent pubertal gynecomastia at 13 and 16 years of age, respectively. Physical examinations revealed breast of Tanner stage 3 and normal male-type external genitalia in both cases. Clinical features such as female-type pubic hair and borderline small testis indicated mildly impaired masculinization. Molecular analysis identified a previously reported p.Arg789Ser mutation in the androgen receptor gene (AR) in the 2 cases. Two months of oral administration of tamoxifen ameliorated gynecomastia to Tanner stage 2 with no adverse events. Additional treatment with testosterone enanthate showed negligible effects on body hair and penile length. Hormone values of the 2 cases during tamoxifen treatment remained similar to those in previously reported untreated patients with PAIS. The results indicate that tamoxifen was effective in treating pubertal gynecomastia in these 2 patients with PAIS and may be considered as a therapeutic option in this situation pending further studies.

Metabolism and transport of tamoxifen in relation to its effectiveness

DEFF Research Database (Denmark)

Cronin-Fenton, Deirdre P; Damkier, Per; Lash, Timothy L

2014-01-01

Tamoxifen reduces the rate of breast cancer recurrence by approximately a half. Tamoxifen is metabolized to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6). Tamoxifen is a substrate for ATP-binding cassette transporter proteins. We review ta...

5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial.

Science.gov (United States)

Wagner-Johnston, Nina D; Sloan, Jeff A; Liu, Heshan; Kearns, Ann E; Hines, Stephanie L; Puttabasavaiah, Suneetha; Dakhil, Shaker R; Lafky, Jacqueline M; Perez, Edith A; Loprinzi, Charles L

2015-08-01

Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results. A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms. © 2015 American Cancer Society.

Compound list: tamoxifen [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available tamoxifen TMX 00054 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/tam...oxifen.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/tam...oxifen.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/tam...open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/tamoxifen.Rat.in_vivo.Liver.Repeat.zip ...

Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

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M.V. Borgo

2011-08-01

Full Text Available Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR. Female SHR were divided into four groups (N = 7 each: sham-operated (SHAM, sham-operated and treated with tamoxifen (10 mg/kg by gavage for 90 days (TAMOX, ovariectomized (OVX, and ovariectomized and treated with tamoxifen (OVX+TAMOX. Mean arterial pressure (MAP, heart rate (HR, coronary perfusion pressure (CPP, and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67%, respectively in the OVX+TAMOX group compared to the OVX group (P < 0.01. The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg when compared to the OVX group (P < 0.01 and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05. Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01. Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

Pak1, adjuvant tamoxifen therapy, and breast cancer recurrence risk in a Danish population-based study

DEFF Research Database (Denmark)

Ahern, Thomas P; Cronin-Fenton, Deirdre P; Lash, Timothy L

2016-01-01

-/TAM - group. Pak1 cytoplasmic intensity was not associated with breast cancer recurrence in either group (ER+/TAM + ORadj for strong vs. no cytoplasmic staining = 0.91, 95% CI 0.57, 1.5; ER-/TAM - ORadj for strong vs. no cytoplasmic staining = 0.74, 95% CI 0.39, 1.4). Associations between Pak1 nuclear......Background Adjuvant tamoxifen therapy approximately halves the risk of estrogen receptor-positive (ER+) breast cancer recurrence, but many women do not respond to therapy. Observational studies nested in clinical trial populations suggest that overexpression or nuclear localization of p21-activated...... by immunohistochemical staining of primary breast tumors from recurrence cases and matched controls from two breast cancer populations; women diagnosed with ER-positive tumors who received at least one year of tamoxifen therapy (ER+/TAM+), and women diagnosed with ER-negative tumors who survived for at least one year...

Augmentation of Endoxifen Exposure in Tamoxifen-Treated Women Following SSRI Switch

NARCIS (Netherlands)

L. Binkhorst (Lisette); M. Bannink (Marjolein); P. de Bruijn (Peter); J.B. Ruit (Jos); J. Droogendijk (Jolanda); R.J. van Alphen (Robbert); T.D. den Boer (Tilly D.); M.H. Lam (Mei); A. Jager (Agnes); T. van Gelder (Teun); A.H.J. Mathijssen (Ron)

2016-01-01

textabstractBackground and Objective: The anti-oestrogen tamoxifen requires metabolic activation to endoxifen by cytochrome P450 (CYP) enzymes, predominantly CYP2D6. Potent CYP2D6-inhibiting antidepressants can seriously disrupt tamoxifen metabolism, probably influencing the efficacy of tamoxifen.

A Role for Estrogen Receptor Phosphorylation in the Resistance to Tamoxifen

International Nuclear Information System (INIS)

De Leeuw, R.; Neefjes, J.; Michalides, R.

2011-01-01

About two thirds of all human breast cancer cases are estrogen receptor positive. The drug of first choice for these patients is tamoxifen. However, about half of the recurrences after removal of the primary tumor are or become resistant to this drug. While many mechanisms have been identified for tamoxifen resistance in the lab, at present only a few have been translated to the clinic. This paper highlights the role in tamoxifen resistance of phosphorylation by different kinases on different sites of the estrogen receptor. We will discuss the molecular pathways and kinases that are involved in phosphorylation of ERa and how these affect tamoxifen resistance. Finally, we will elaborate on the clinical translation of these observations and the possibility to predict tamoxifen responses in patient tumor samples before treatment onset. The findings made originally on the bench may translate into a better and personalized treatment of breast cancer patients using an old and safe anticancer drug: tamoxifen

ATLAS: Adjuvant Tamoxifen Longer Against Shorter

Science.gov (United States)

1998-09-01

largely tunaffected by other these 30 000 women during about 10 years of follow-up patient characteristics or treatments. were 21% (SD 3), 29% (SD 2...for both types of mosted to stop part of the eduon y epatient . most of them did stop, part of the reduction in the The right side of figure 4...patient characteristics (e.g. high/ low-risk, ER+/ER-, pre/post-menopausal) recorded at entry. Other trials of tamoxifen duration The Atlas collaboration

Tumor specific HMG-CoA reductase expression in primary pre-menopausal breast cancer predicts response to tamoxifen

LENUS (Irish Health Repository)

Brennan, Donal J

2011-01-31

Abstract Introduction We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. Methods HMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response. Results HMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive\\/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as

The effect of tamoxifen on pubertal bone development in adolescents with pubertal gynecomastia.

Science.gov (United States)

Akgül, Sinem; Derman, Orhan; Kanbur, Nuray

2016-01-01

During puberty, estrogen has a biphasic effect on epiphyses; at low levels, it leads to an increase in height and bone mass, whereas at high levels, it leads to closure of the epiphysis. Tamoxifen is a selective estrogen receptor modulator that has been used in the treatment of pubertal gynecomastia. Although it has not been approved for this indication, studies have shown it to be both successful and safe. In males, the peak of pubertal bone development occurs during Tanner stage 3-4, which is also when pubertal gynecomastia reaches its highest prevalence. Thus tamoxifen treatment could potentially effect pubertal bone development. The aim of this study was to assess the effects of tamoxifen on bone mineral density (BMD) and skeletal maturation when used for pubertal gynecomastia. We evaluated 20 boys with pubertal gynecomastia receiving tamoxifen for at least 4 months. BMD was measured with dual-energy X-ray absorptiometry. Z-score and absolute BMD (g/cm(2)) was determined at baseline and 2 months after completing tamoxifen treatment. Bone age and height was evaluated before treatment and again one year later. Using absolute BMD (g/cm(2)), the mean difference from baseline was significant between the two groups both at spine (p=0.002) and femur (p=0.001), but not with the Z-score. This result was attributed to the expected increase during puberty according to sex and age. No significant effect on skeletal maturation was found (p=1.112). We conclude that when pubertal bone development is concerned, tamoxifen is safe for the treatment of pubertal gynecomastia as neither bone mineralization nor growth potential was affected.

Effect of Tamoxifen on Seminiferous Tubules Structure during Pregnancy in Adult Mice

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J Soleimani Rad

2016-03-01

Full Text Available Introduction: Tamoxifen is a nonsteroidal drug which mainly treats breast cancer. It is also applied for stimulation of ovulation and remedy of infertility. Regarding the tamoxifen binding to estrogen receptors and the possible role of estrogens in spermatogenesis, the present study aimed to histologically evaluate spermatogenesis in the seminiferous ducts of mice, whose mothers had received tamoxifen during pregnancy. Methods: In the present study, 30 female and 15 male mice of NMRI race were selected for mating. Since 13th day of pregnancy, the experimental group received tamoxifen with the dosage of 5 mg/kg intra-peritoneally for 7 days, wherease the control group received normal saline. After childbirth of the mated mice, male infants were selected and monitored in the standard laboratory conditions. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation, and the testes were removed for histological evaluation of spermatogenesis. After routine histological processing, the samples were studied by the light microscope. Results: Histological studies showed that spermatogenic and Sertoli cells in the seminiferous tubules in control and experimental groups were significantly different, though no difference was observed in the number of Leydig cells in the both groups. Conclusion: The findings of the present study showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility in the male rat.

Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma

International Nuclear Information System (INIS)

Ma, Ji; Zhang, Jian; Liu, Wenchao; Guo, Yan; Chen, Suning; Zhong, Cuiping; Xue, Yan; Zhang, Yuan; Lai, Xiaofeng; Wei, Yifang; Yu, Shentong

2014-01-01

Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). However, many ER-positive patients are low reactive or resistant to tamoxifen. Metformin is a widely used anti-diabetic drug with noteworthy anti-cancer effects. We investigated whether metformin has the additive effects with tamoxifen in ER-positive breast cancer therapy. The efficacy of metformin alone and in combination with tamoxifen against ER-positive breast cancer was analyzed by cell survival, DNA replication activity, plate colony formation, soft-agar, flow cytometry, immunohistochemistry, and nude mice model assays. The involved signaling pathways were detected by western blot assay. When metformin was combined with tamoxifen, the concentration of tamoxifen required for growth inhibition was substantially reduced. Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells. In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Finally, two-drug combination therapy significantly inhibited tumor growth in vivo. The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer

Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat

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Goldstein Irwin

2006-09-01

Full Text Available Abstract Background Tamoxifen, a selective estrogen receptor modulator with both estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in breast cancer patients. Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat. Methods Female Sprague-Dawley rats were subjected to sham surgery or bilateral ovariectomy. After 2 weeks, sham-operated rats were implanted with subcutaneous osmotic infusion pumps containing vehicle (control or tamoxifen (150 μg/day. Ovariectomized rats were similarly infused with vehicle. After an additional 2 weeks, vaginal blood flow responses to pelvic nerve stimulation were measured by laser Doppler flowmetry and vaginal tissue was collected for histological and biochemical assay. Results Tamoxifen treatment did not change plasma estradiol concentrations relative to control animals, while ovariectomized rats exhibited a 60% decrease in plasma estradiol. Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight. Vaginal blood flow was significantly decreased in tamoxifen-infused rats compared to controls. Similar to ovariectomized animals, estrogen receptor binding was increased and arginase enzyme activity was decreased in tamoxifen-infused rats. However, different from control and ovariectomized animals, the vaginal epithelium in tamoxifen-infused rats appeared highly mucified. Periodic acid-Schiff staining confirmed a greater production of carbohydrate-rich compounds (e.g. mucin, glycogen by the vaginal epithelium of tamoxifen-infused rats. Conclusion The observations suggest that tamoxifen exerts both anti-estrogenic and pro

Estrogen receptor, Progesterone receptor, HER2 status and Ki67 index and responsiveness to adjuvant tamoxifen in postmenopausal high-risk breast cancer patients enrolled in the DBCG 77C trial

DEFF Research Database (Denmark)

Knoop, Ann; Lænkholm, Anne Vibeke; Jensen, M. B.

2014-01-01

BCRR and BCM in postmenopausal patients with ER positive breast cancers. The relative benefit from tamoxifen was not significantly different in luminal A and B subtypes. Funding: The Danish Breast Cancer Cooperative Group (DBCG) prepared the original protocol (DBCG 77C) and was the sponsor of the study......Background: The DBCG 77C trial compared one year of tamoxifen in postmenopausal, steroid-receptor unknown, high-risk breast cancer patients to no adjuvant systemic therapy. After a potential follow-up of 30 years we report overall efficacy of the study and results according to subtypes subsequently...... assessed by immunohistochemistry and fluorescent in situ hybridisation (FISH). Methods: Between 1977 and 1982, 1716 postmenopausal patients with tumours larger than 5 cm or positive axillary nodes were randomly assigned to no systemic therapy or tamoxifen 30 mg daily for one year. Archival tumour tissue...

Tamoxifen dosing for Cre-mediated recombination in experimental bronchopulmonary dysplasia.

Science.gov (United States)

Ruiz-Camp, Jordi; Rodríguez-Castillo, José Alberto; Herold, Susanne; Mayer, Konstantin; Vadász, István; Tallquist, Michelle D; Seeger, Werner; Ahlbrecht, Katrin; Morty, Rory E

2017-02-01

Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth characterized by blunted post-natal lung development. BPD can be modelled in mice by exposure of newborn mouse pups to elevated oxygen levels. Little is known about the mechanisms of perturbed lung development associated with BPD. The advent of transgenic mice, where genetic rearrangements can be induced in particular cell-types at particular time-points during organogenesis, have great potential to explore the pathogenic mechanisms at play during arrested lung development. Many inducible, conditional transgenic technologies available rely on the application of the estrogen-receptor modulator, tamoxifen. While tamoxifen is well-tolerated and has been widely employed in adult mice, or in healthy developing mice; tamoxifen is not well-tolerated in combination with hyperoxia, in the most widely-used mouse model of BPD. To address this, we set out to establish a safe and effective tamoxifen dosing regimen that can be used in newborn mouse pups subjected to injurious stimuli, such as exposure to elevated levels of environmental oxygen. Our data reveal that a single intraperitoneal dose of tamoxifen of 0.2 mg applied to newborn mouse pups in 10 μl Miglyol vehicle was adequate to successfully drive Cre recombinase-mediated genome rearrangements by the fifth day of life, in a murine model of BPD. The number of recombined cells was comparable to that observed in regular tamoxifen administration protocols. These findings will be useful to investigators where tamoxifen dosing is problematic in the background of injurious stimuli and mouse models of human and veterinary disease.

Analysis of the Ki-67 index in the vaginal epithelium of castrated rats treated with tamoxifen

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Afif Rieth Nery-Aguiar

2016-02-01

Full Text Available OBJECTIVES: Vaginal atrophy and breast cancer are common conditions in postmenopausal women and tamoxifen is the standard endocrine treatment for hormone-sensitive tumors. The present study aimed to assess the effect of tamoxifen on Ki-67 protein expression in the vaginal epithelium of castrated rats. MATERIAL AND METHODS: Forty Wistar-Hannover adult, virgin, castrated rats were randomly divided into two groups, group I (control, n=20 and group II (tamoxifen, n=20, receiving 0.5 ml of propylene glycol and 250 µg of tamoxifen diluted in 0.5 ml of propylene glycol, respectively, daily by gavage for 30 days. On the 31st day, the rats were euthanized and their vaginas were removed and fixed in 10% buffered formalin for the immunohistochemical study of Ki-67 protein expression. Data were analyzed by the Levene and Student’s t tests (p<0.05. RESULTS: The mean index of Ki-67 expression in the rat vagina of groups I and II was 4.04±0.96 and 26.86±2.19, respectively (p<0.001. CONCLUSIONS: According to the results of the present study, tamoxifen, at the dose and treatment length used, induced a significant increase in the cell proliferation of the vaginal mucosa in castrated rats, as evaluated by Ki-67 protein expression.

Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

Energy Technology Data Exchange (ETDEWEB)

Zheng, Kai [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of Life Science and Technology, Jinan University, Guangzhou (China); Chen, Maoyun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Xiang, Yangfei; Ma, Kaiqi [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Jin, Fujun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Wang, Xiao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Wang, Xiaoyan; Wang, Shaoxiang [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Wang, Yifei, E-mail: twang-yf@163.com [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China)

2014-04-18

Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

International Nuclear Information System (INIS)

Zheng, Kai; Chen, Maoyun; Xiang, Yangfei; Ma, Kaiqi; Jin, Fujun; Wang, Xiao; Wang, Xiaoyan; Wang, Shaoxiang; Wang, Yifei

2014-01-01

Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections

Bilateral macular edema in a patient treated with tamoxifen: a case report and review of the literature.

Science.gov (United States)

Zafeiropoulos, Paraskevas; Nanos, Panagiotis; Tsigkoulis, Evangelos; Stefaniotou, Maria

2014-01-01

We present a case of a 41-year-old female patient with progressive bilateral visual loss. On examination, her best corrected visual acuity (BCVA) in her right eye was 3/10 and her BCVA in her left eye was 2/10. Fundus and optical coherence tomography examination revealed severe bilateral macular edema. She had been diagnosed with breast cancer 6 years ago and was receiving tamoxifen at a dosage of 20 mg/day ever since. Tamoxifen therapy was discontinued, and the patient received 250 mg of acetazolamide three times a day for a period of 1 month. Both foveae regained their normal contour within 2 months, and her vision was restored to 10/10 BCVA 3 months later. To our knowledge, this is the first case reported where bilateral intraretinal macular edema is the only retinal manifestation in a patient on oral tamoxifen.

Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

DEFF Research Database (Denmark)

Joshi, Tejal; Elias, Daniel; Stenvang, Jan

2016-01-01

Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of mi......+ breast cancer patients receiving adjuvant tamoxifen mono-therapy. Our results provide new insight into the molecular mechanisms of tamoxifen resistance and may form the basis for future medical intervention for the large number of women with tamoxifen-resistant ER+ breast cancer.......RNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all Tam...

CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

International Nuclear Information System (INIS)

Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

2013-01-01

Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

Energy Technology Data Exchange (ETDEWEB)

Prather, Paul L. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M. [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Ford, Benjamin M.; Franks, Lirit N. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Radominska-Pandya, Anna, E-mail: RadominskaAnna@uams.edu [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States)

2013-11-15

Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

Gene expression profiling identifies FYN as an important molecule in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy

DEFF Research Database (Denmark)

Elias, D; (Hansen) Vever, Henriette; Lænkholm, A-V

2015-01-01

To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer, we performed gene array analyses and identified 366 genes with altered expression in four unique tamoxifen-resistant (TamR) cell lines vs the parental tamoxifen-sensitive MCF-7/S0.5 cell line. Most of these genes were...

Adjuvant tamoxifen influences the lipid profile in breast cancer patients.

Science.gov (United States)

Lin, Che; Chen, Li-Sheng; Kuo, Shou-Jen; Chen, Dar-Ren

2014-02-01

Currently there is a debate regarding whether tamoxifen used in breast cancer has an impact on lipid profiles. The aim of this study was to determine whether tamoxifen has an impact on the serum lipid profile in Taiwanese women. Data of 109 patients were collected from the routine clinical follow-up for women with hormone receptor-positive breast cancer who were treated between July 2005 and March 2008. These patients were divided into 2 subgroups, based on their tumor grade and lymph node status. Subgroup 1 patients had tumor grade I/II and a negative lymph node status. Those patients with tumor grade III or a positive lymph node status were defined as subgroup 2. In the 109 patients, the mean serum total cholesterol (TC) levels after tamoxifen treatment, as well as the serum low-density lipoprotein cholesterol (LDL-C) levels, were lower than the baseline levels, with statistically significant differences. Treatment with tamoxifen lowered the serum TC and LDL-C levels in both subgroups. The results indicate that tamoxifen has an impact on the serum lipid profile of breast cancer patients in Taiwan. Physicians should follow up the lipid profile in these patients.

C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells.

Science.gov (United States)

Li, Wei; Xu, Ling; Che, Xiaofang; Li, Haizhou; Zhang, Ye; Song, Na; Wen, Ti; Hou, Kezuo; Yang, Yi; Zhou, Lu; Xin, Xing; Xu, Lu; Zeng, Xue; Shi, Sha; Liu, Yunpeng; Qu, Xiujuan; Teng, Yuee

2018-05-02

Tamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance. MTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence. SiRNA was used to examine the function of HER2 in of BT474 cells. An in vivo xenograft animal model was established to examine the role of c-Cbl in tumor growth. MTT and colony formation assay showed that BT474 cells are resistant to tamoxifen and T47D cells are sensitive to tamoxifen. Immunoprecipitation experiments revealed ER-c-Src-HER2 complex formation in BT474 cells but not in T47D cells. However, ER-c-Src-HER2 complex formation was detected after overexpressing HER2 in T47D cells and these cells were more resistant to tamoxifen. HER2 knockdown by siRNA in BT474 cells reduced ER-c-Src-HER2 complex formation and reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was also disrupted and tamoxifen resistance was reversed in BT474 cells by the c-Src inhibitor PP2 and HER2 antibody trastuzumab. Nystatin, a lipid raft inhibitor, reduced ER-c-Src-HER2 complex formation and partially reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was disrupted by overexpression of c-Cbl but not by the c-Cbl ubiquitin ligase mutant. In addition, c-Cbl could reverse tamoxifen resistance in BT474 cells, but the ubiquitin ligase mutant had no effect. The effect of c-Cbl was validated in BT474 tumor-bearing nude mice in vivo. Immunofluorescence also revealed ER-c-Src-HER2 complex formation was reduced in tumor tissues of nude mice with c-Cbl overexpression. Our results suggested that c-Cbl can reverse tamoxifen

Tamoxifen treatment in hamsters induces protection during taeniosis by Taenia solium.

Science.gov (United States)

Escobedo, Galileo; Palacios-Arreola, M Isabel; Olivos, Alfonso; López-Griego, Lorena; Morales-Montor, Jorge

2013-01-01

Human neurocysticercosis by Taenia solium is considered an emergent severe brain disorder in developing and developed countries. Discovery of new antiparasitic drugs has been recently aimed to restrain differentiation and establishment of the T. solium adult tapeworm, for being considered a central node in the disease propagation to both pigs and humans. Tamoxifen is an antiestrogenic drug with cysticidal action on Taenia crassiceps, a close relative of T. solium. Thus, we evaluated the effect of tamoxifen on the in vitro evagination and the in vivo establishment of T. solium. In vitro, tamoxifen inhibited evagination of T. solium cysticerci in a dose-time dependent manner. In vivo, administration of tamoxifen to hamsters decreased the intestinal establishment of the parasite by 70%, while recovered tapeworms showed an 80% reduction in length, appearing as scolices without strobilar development. Since tamoxifen did not show any significant effect on the proliferation of antigen-specific immune cells, intestinal inflammation, and expression of Th1/Th2 cytokines in spleen and duodenum, this drug could exert its antiparasite actions by having direct detrimental effects upon the adult tapeworm. These results demonstrate that tamoxifen exhibits a strong cysticidal and antitaeniasic effect on T. solium that should be further explored in humans and livestock.

Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

Science.gov (United States)

Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

2015-01-01

Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

Bilateral Macular Edema in a Patient Treated with Tamoxifen: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Paraskevas Zafeiropoulos

2014-12-01

Full Text Available We present a case of a 41-year-old female patient with progressive bilateral visual loss. On examination, her best corrected visual acuity (BCVA in her right eye was 3/10 and her BCVA in her left eye was 2/10. Fundus and optical coherence tomography examination revealed severe bilateral macular edema. She had been diagnosed with breast cancer 6 years ago and was receiving tamoxifen at a dosage of 20 mg/day ever since. Tamoxifen therapy was discontinued, and the patient received 250 mg of acetazolamide three times a day for a period of 1 month. Both foveae regained their normal contour within 2 months, and her vision was restored to 10/10 BCVA 3 months later. To our knowledge, this is the first case reported where bilateral intraretinal macular edema is the only retinal manifestation in a patient on oral tamoxifen.

“Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice

International Nuclear Information System (INIS)

Sun, Xueying; Jiang, Ruohan; Przepiorski, Aneta; Reddy, Shiva; Palmano, Kate P; Krissansen, Geoffrey W

2012-01-01

Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers. In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg) were fed an Fe-Lf supplemented diet (5 g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed. Tamoxifen weakly (IC 50 ~ 8 μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations in vitro. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P < 0.001), respectively, compared to untreated controls. The combination therapy was significantly (all P < 0.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors. The results indicate that Fe-Lf is a potent

“Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice

Energy Technology Data Exchange (ETDEWEB)

Sun, Xueying [Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1005 (New Zealand); Department of General Surgery, The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001 (China); Jiang, Ruohan; Przepiorski, Aneta; Reddy, Shiva [Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1005 (New Zealand); Palmano, Kate P [Fonterra Research Centre, Palmerston North, 4442 (New Zealand); Krissansen, Geoffrey W [Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1005 (New Zealand)

2012-12-11

Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers. In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg) were fed an Fe-Lf supplemented diet (5 g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed. Tamoxifen weakly (IC{sub 50} ~ 8 μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations in vitro. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P < 0.001), respectively, compared to untreated controls. The combination therapy was significantly (all P < 0.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors. The results indicate that Fe-Lf is a

Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

Science.gov (United States)

Rossi, Emanuela; Morabito, Alessandro; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; De Maio, Ermelinda; Di Maio, Massimo; Piccirillo, Maria Carmela; De Feo, Gianfranco; D'Aiuto, Giuseppe; Botti, Gerardo; Chiodini, Paolo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2009-07-01

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

Tamoxifen induces regression of estradiol-induced mammary cancer in ACI.COP-Ept2 rat model

OpenAIRE

Ruhlen, Rachel L.; Willbrand, Dana M.; Besch-Williford, Cynthia L.; Ma, Lixin; Shull, James D.; Sauter, Edward R.

2008-01-01

The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5–7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonan...

Bioanalytical methods for determination of tamoxifen and its phase I metabolites: A review

International Nuclear Information System (INIS)

Teunissen, S.F.; Rosing, H.; Schinkel, A.H.; Schellens, J.H.M.; Beijnen, J.H.

2010-01-01

The selective estrogen receptor modulator tamoxifen is used in the treatment of early and advanced breast cancer and in selected cases for breast cancer prevention in high-risk subjects. The cytochrome P450 enzyme system and flavin-containing monooxygenase are responsible for the extensive metabolism of tamoxifen into several phase I metabolites that vary in toxicity and potencies towards estrogen receptor (ER) alpha and ER beta. An extensive overview of publications on the determination of tamoxifen and its phase I metabolites in biological samples is presented. In these publications techniques were used such as capillary electrophoresis, liquid, gas and thin layer chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection, liquid scintillation counting and nuclear magnetic resonance spectroscopy). A trend is seen towards the use of liquid chromatography coupled to mass spectrometry (LC-MS). State-of-the-art LC-MS equipment allowed for identification of unknown metabolites and quantification of known metabolites reaching lower limit of quantification levels in the sub pg mL -1 range. Although tamoxifen is also metabolized into phase II metabolites, the number of publications reporting on phase II metabolism of tamoxifen is scarce. Therefore the focus of this review is on phase I metabolites of tamoxifen. We conclude that in the past decades tamoxifen metabolism has been studied extensively and numerous metabolites have been identified. Assays have been developed for both the identification and quantification of tamoxifen and its metabolites in an array of biological samples. This review can be used as a resource for method transfer and development of analytical methods used to support pharmacokinetic and pharmacodynamic studies of tamoxifen and its phase I metabolites.

Preoperative psychosocial risk factors for poor outcomes at 1 and 5 years after total knee replacement.

Science.gov (United States)

Wylde, Vikki; Trela-Larsen, Lea; Whitehouse, Michael R; Blom, Ashley W

2017-10-01

Background and purpose - Psychosocial factors are important risk factors for poor outcomes in the first year after total knee replacement (TKR), however their impact on long-term outcomes is unclear. We aimed to identify preoperative psychosocial risk factors for poor outcomes at 1 year and 5 years after TKR. Patients and methods - 266 patients were recruited prior to TKR surgery. Knee pain and function were assessed preoperatively and at 1 and 5 years postoperative using the WOMAC Pain score, WOMAC Function score and American Knee Society Score (AKSS) Knee score. Preoperative depression, anxiety, catastrophizing, pain self-efficacy and social support were assessed. Statistical analyses involved multiple linear regression and mixed effect linear regression. Results - Higher anxiety was a risk factor for worse pain at 1 year postoperative. No psychosocial factors were associated with any outcomes at 5 years postoperative. Analysis of change over time found that patients with higher pain self-efficacy had lower preoperative pain and experienced less improvement in pain up to 1 year postoperative. Higher pain self-efficacy was associated with less improvement in the AKSS up to 1 year postoperative but more improvement between 1 and 5 years postoperative. Interpretation - Preoperative anxiety was found to influence pain at 1 year after TKR. However, none of the psychosocial variables were risk factors for a poor outcome at 5 years post-operative, suggesting that the negative effects of anxiety on outcome do not persist in the longer-term.

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.

Science.gov (United States)

Cuzick, Jack; Sestak, Ivana; Cawthorn, Simon; Hamed, Hisham; Holli, Kaija; Howell, Anthony; Forbes, John F

2015-01-01

Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation. In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928. Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], pbreast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0

A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study

International Nuclear Information System (INIS)

Gu, Ran; Long, Meijun; Chen, Kai; Chen, Lili; Xiao, Qiaozhen; Wu, Mei; Song, Erwei; Su, Fengxi; Jia, Weijuan; Zeng, Yunjie; Rao, Nanyan; Hu, Yue; Li, Shunrong; Wu, Jiannan; Jin, Liang; Chen, Lijuan

2012-01-01

In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. Toremifene may be a valid and

Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children's Oncology Group (COG) phase II study.

Science.gov (United States)

Skapek, Stephen X; Anderson, James R; Hill, D Ashley; Henry, David; Spunt, Sheri L; Meyer, William; Kao, Simon; Hoffer, Fredric A; Grier, Holcombe E; Hawkins, Douglas S; Raney, R Beverly

2013-07-01

Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group. Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT. Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. Copyright © 2012 Wiley Periodicals, Inc.

Smart coumarin-tagged imprinted polymers for the rapid detection of tamoxifen.

Science.gov (United States)

Ray, Judith V; Mirata, Fosca; Pérollier, Celine; Arotcarena, Michel; Bayoudh, Sami; Resmini, Marina

2016-03-01

A signalling molecularly imprinted polymer was synthesised for easy detection of tamoxifen and its metabolites. 6-Vinylcoumarin-4-carboxylic acid (VCC) was synthesised from 4-bromophenol to give a fluorescent monomer, designed to switch off upon binding of tamoxifen. Clomiphene, a chlorinated analogue, was used as the template for the imprinting, and its ability to quench the coumarin fluorescence when used in a 1:1 ratio was demonstrated. Tamoxifen and 4-hydroxytamoxifen were also shown to quench coumarin fluorescence. Imprinted and non-imprinted polymers were synthesised using VCC, methacrylic acid as a backbone monomer and ethylene glycol dimethacrylate as cross-linker, and were ground and sieved to particle sizes ranging between 45 and 25 μm. Rebinding experiments demonstrate that the imprinted polymer shows very strong affinity for both clomiphene and tamoxifen, while the non-imprinted polymer shows negligible rebinding. The fluorescence of the imprinted polymer is quenched by clomiphene, tamoxifen and 4-hydroxytamoxifen. The switch off in fluorescence of the imprinted polymer under these conditions could also be detected under a UV lamp with the naked eye, making this matrix suitable for applications when coupled with a sample preparation system.

Patient-reported outcomes 5 years after laser in situ keratomileusis.

Science.gov (United States)

Schallhorn, Steven C; Venter, Jan A; Teenan, David; Hannan, Stephen J; Hettinger, Keith A; Pelouskova, Martina; Schallhorn, Julie M

2016-06-01

To assess vision-related, quality-of-life outcomes 5 years after laser in situ keratomileusis (LASIK) and determine factors predictive of patient satisfaction. Optical Express, Glasgow, Scotland. Retrospective case series. Data from patients who had attended a clinical examination 5 years after LASIK were analyzed. All treatments were performed using the Visx Star S4 IR excimer laser. Patient-reported satisfaction, the effect of eyesight on various activities, visual phenomena, and ocular discomfort were evaluated 5 years postoperatively. Multivariate regression analysis was performed to determine factors affecting patient satisfaction. The study comprised 2530 patients (4937 eyes) who had LASIK. The mean age at the time of surgery was 42.4 years ± 12.5 (SD), and the preoperative manifest spherical equivalent ranged from -11.0 diopters (D) to +4.88 D. Five years postoperatively, 79.3% of eyes were within ±0.50 D of emmetropia and 77.7% of eyes achieved monocular uncorrected distance visual acuity (UDVA) and 90.6% of eyes achieved binocular UDVA of 20/20 or better. Of the patients, 91.0% said they were satisfied with their vision and 94.9% did not wear distance correction. Less than 2.0% of patients noticed visual phenomena, even with spectacle correction. Major predictors of patient satisfaction 5 years postoperatively were postoperative binocular UDVA (37.6% variance explained by regression model), visual phenomena (relative contribution of 15.0%), preoperative and postoperative sphere and their interactions (11.6%), and eyesight-related difficulties with various activities such as night driving, outdoor activities, and reading (10.2%). Patient-reported quality-of-life and satisfaction rates remained high 5 years after LASIK. Uncorrected vision was the strongest predictor of satisfaction. Dr. S.C. Schallhorn is a consultant to Abbott Medical Optics, Inc., Zeiss Meditec AG, and Autofocus Inc. and a global medical director for Optical Express. No other

Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization

International Nuclear Information System (INIS)

Wang Ying; He Qingyu; Chen Hongming; Chiu Jenfu

2007-01-01

The anti-estrogen tamoxifen and vitamin A-related compound, all-trans retinoic acid (RA), in combination act synergistically to inhibit the growth of MCF-7 human breast cancer cells. In the present study, we applied two-dimensional gel electrophoresis based proteomic approach to globally analyze this synergistic effect of RA and tamoxifen. Proteomic study revealed that multiple clusters of proteins were involved in RA and tamoxifen-induced apoptosis in MCF-7 breast cancer cells, including post-transcriptional and splicing factors, proteins related to cellular proliferation or differentiation, and proteins related to energy production and internal degradation systems. The negative growth factor-transforming growth factor β (TGFβ) was secreted by RA and/or tamoxifen treatment and was studies as a potential mediator of the synergistic effects of RA and tamoxifen in apoptosis. By comparing protein alterations in treatments of RA and tamoxifen alone or in combination to those of TGFβ treatment, or co-treatment with TGFβ inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGFβ signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGFβ signaling pathway in breast cancer cells

Physiologically-based pharmacokinetic modeling of tamoxifen and its metabolites in women of different CYP2D6 phenotypes provides new insight into the tamoxifen mass balance

Directory of Open Access Journals (Sweden)

Kristin eDickschen

2012-05-01

Full Text Available Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER+ mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6. It is widely accepted that CYP2D6 poor metabolizers (PM exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers (EM. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved.In this context, physiologically-based pharmacokinetic (PBPK-modeling provides a useful tool to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy.It has long been thought that only a minor percentage of endoxifen is formed via 4-hydroxytamoxifen. However, the current investigation supports very recently published data that postulates a contribution of 4-hydroxytamoxifen above 20 % to total endoxifen formation. The developed PBPK-model describes tamoxifen PK in rats and humans. Moreover, tamoxifen metabolism in dependence of CYP2D6 phenotype in populations of European female individuals is well described, thus providing a good basis to further investigate the linkage of PK, mode of action, and treatment outcome in dependence of factors such as phenotype, ethnicity or co-treatment with CYP2D6 inhibitors.

The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer

International Nuclear Information System (INIS)

Loh, Yan Ni; Hedditch, Ellen L; Baker, Laura A; Jary, Eve; Ward, Robyn L; Ford, Caroline E

2013-01-01

Acquired resistance to Tamoxifen remains a critical problem in breast cancer patient treatment, yet the underlying causes of resistance have not been fully elucidated. Abberations in the Wnt signalling pathway have been linked to many human cancers, including breast cancer, and appear to be associated with more metastatic and aggressive types of cancer. Here, our aim was to investigate if this key pathway was involved in acquired Tamoxifen resistance, and could be targeted therapeutically. An in vitro model of acquired Tamoxifen resistance (named TamR) was generated by growing the estrogen receptor alpha (ER) positive MCF7 breast cancer cell line in increasing concentrations of Tamoxifen (up to 5 uM). Alterations in the Wnt signalling pathway and epithelial to mesenchymal transition (EMT) in response to Tamoxifen and treatment with the Wnt inhibitor, IWP-2 were measured via quantitative RT-PCR (qPCR) and TOP/FOP Wnt reporter assays. Resistance to Tamoxifen, and effects of IWP-2 treatment were determined by MTT proliferation assays. TamR cells exhibited increased Wnt signalling as measured via the TOP/FOP Wnt luciferase reporter assays. Genes associated with both the β-catenin dependent (AXIN2, MYC, CSNK1A1) and independent arms (ROR2, JUN), as well as general Wnt secretion (PORCN) of the Wnt signalling pathway were upregulated in the TamR cells compared to the parental MCF7 cell line. Treatment of the TamR cell line with human recombinant Wnt3a (rWnt3a) further increased the resistance of both MCF7 and TamR cells to the anti-proliferative effects of Tamoxifen treatment. TamR cells demonstrated increased expression of EMT markers (VIM, TWIST1, SNAI2) and decreased CDH1, which may contribute to their resistance to Tamoxifen. Treatment with the Wnt inhibitor, IWP-2 inhibited cell proliferation and markers of EMT. These data support the role of the Wnt signalling pathway in acquired resistance to Tamoxifen. Further research into the mechanism by which activated Wnt

Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice

International Nuclear Information System (INIS)

Hesselbarth, Nico; Pettinelli, Chiara; Gericke, Martin; Berger, Claudia; Kunath, Anne; Stumvoll, Michael; Blüher, Matthias; Klöting, Nora

2015-01-01

Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA 1c , triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects. - Highlights: • Tamoxifen treatment causes significantly increased HbA 1c , triglyceride and free fatty acid serum concentrations. • Tamoxifen induces browning of subcutaneous AT and increased UCP-1 expression. • Tamoxifen changes adipocyte size distribution, and transient body composition

Preoperative MRI findings predict two-year postoperative clinical outcome in lumbar spinal stenosis.

Directory of Open Access Journals (Sweden)

Pekka Kuittinen

Full Text Available To study the predictive value of preoperative magnetic resonance imaging (MRI findings for the two-year postoperative clinical outcome in lumbar spinal stenosis (LSS.84 patients (mean age 63±11 years, male 43% with symptoms severe enough to indicate LSS surgery were included in this prospective observational single-center study. Preoperative MRI of the lumbar spine was performed with a 1.5-T unit. The imaging protocol conformed to the requirements of the American College of Radiology for the performance of MRI of the adult spine. Visual and quantitative assessment of MRI was performed by one experienced neuroradiologist. At the two-year postoperative follow-up, functional ability was assessed with the Oswestry Disability Index (ODI 0-100% and treadmill test (0-1000 m, pain symptoms with the overall Visual Analogue Scale (VAS 0-100 mm, and specific low back pain (LBP and specific leg pain (LP separately with a numeric rating scale from 0-10 (NRS-11. Satisfaction with the surgical outcome was also assessed.Preoperative severe central stenosis predicted postoperatively lower LP, LBP, and VAS when compared in patients with moderate central stenosis (p<0.05. Moreover, severe stenosis predicted higher postoperative satisfaction (p = 0.029. Preoperative scoliosis predicted an impaired outcome in the ODI (p = 0.031 and lowered the walking distance in the treadmill test (p = 0.001. The preoperative finding of only one stenotic level in visual assessment predicted less postoperative LBP when compared with patients having 2 or more stenotic levels (p = 0.026. No significant differences were detected between quantitative measurements and the patient outcome.Routine preoperative lumbar spine MRI can predict the patient outcome in a two-year follow up in patients with LSS surgery. Severe central stenosis and one-level central stenosis are predictors of good outcome. Preoperative finding of scoliosis may indicate worse functional ability.

Safety and Efficacy of High-Dose Tamoxifen and Sulindac for Desmoid Tumor in Children: Results of a Children’s Oncology Group (COG) Phase II Study

Science.gov (United States)

Skapek, Stephen X.; Anderson, James R.; Hill, D. Ashley; Henry, David; Spunt, Sheri L.; Meyer, William; Kao, Simon; Hoffer, Fredric A.; Grier, Holcombe E.; Hawkins, Douglas S.; Raney, R. Beverly

2015-01-01

Background Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children’s Oncology Group. Procedures Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Results Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10–18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23–0.48) and 96%, respectively. All three deaths were due to progressive DT. Conclusions Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. PMID:23281268

Dextromethorphan as a phenotyping test to predict endoxifen exposure in patients on tamoxifen treatment.

Science.gov (United States)

de Graan, Anne-Joy M; Teunissen, Sebastiaan F; de Vos, Filip Y F L; Loos, Walter J; van Schaik, Ron H N; de Jongh, Felix E; de Vos, Aad I; van Alphen, Robbert J; van der Holt, Bronno; Verweij, Jaap; Seynaeve, Caroline; Beijnen, Jos H; Mathijssen, Ron H J

2011-08-20

Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the value of CYP2D6 genotyping to reduce the variable efficacy have been reported. In this pharmacokinetic study, we investigated the value of dextromethorphan, a known probe drug for both CYP2D6 and CYP3A enzymatic activity, as a potential phenotyping probe for tamoxifen pharmacokinetics. In this prospective study, 40 women using tamoxifen for invasive breast cancer received a single dose of dextromethorphan 2 hours after tamoxifen intake. Dextromethorphan, tamoxifen, and their respective metabolites were quantified. Exposure parameters of all compounds were estimated, log transformed, and subsequently correlated. A strong and highly significant correlation (r = -0.72; P dextromethorphan (0 to 6 hours) and endoxifen (0 to 24 hours). Also, the area under the plasma concentration-time curve of dextromethorphan (0 to 6 hours) and daily trough endoxifen concentration was strongly correlated (r = -0.70; P dextromethorphan exposure. Dextromethorphan exposure after a single administration adequately predicted endoxifen exposure in individual patients with breast cancer taking tamoxifen. This test could contribute to the personalization and optimization of tamoxifen treatment, but it needs additional validation and simplification before being applicable in future dosing strategies.

The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause

DEFF Research Database (Denmark)

Chirgwin, Jacquie; Sun, Zhuoxin; Smith, Ian

2012-01-01

subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen......) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤ 55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither...... of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤ 55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients...

Therapeutic Effects of a Traditional Chinese Medicine Formula Plus Tamoxifen vs. Tamoxifen for the Treatment of Mammary Gland Hyperplasia: A Meta-Analysis of Randomized Trials

Science.gov (United States)

Li, Hao-Tian; Liu, Hong-Hong; Yang, Yu-Xue; Wang, Tao; Zhou, Xue-Lin; Yu, Yang; Li, Su-Na; Zheng, Yi; Zhang, Ping; Wang, Rui-Lin; Li, Jian-Yu; Wei, Shi-Zhang; Li, Kun; Li, Peng-Yan; Qian, Li-Qi

2018-01-01

As a common disorder that accounts for over 70% of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients' life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09–4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28–0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72–2.71; P < 0.00001) and decrease the size of breast lump (MD: −0.67; 95% CI: −0.86 to −0.49; P < 0.00001) to a greater extent, which might provide a possible explanation for the pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH. PMID:29456506

Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer.

Science.gov (United States)

Osipo, Clodia; Gajdos, Csaba; Liu, Hong; Chen, Bin; Jordan, V Craig

2003-11-05

Long-term tamoxifen treatment of breast cancer can result in tamoxifen-stimulated breast cancer, in which estrogen inhibits tumor growth after tamoxifen withdrawal. We investigated the molecular mechanism(s) of estradiol-induced tumor regression by using an in vivo model of tamoxifen-stimulated human breast cancer. Growth of parental estradiol-stimulated MCF-7E2 and long-term tamoxifen-stimulated MCF-7TAMLT xenografts in athymic mice was measured during treatment with vehicle, estradiol, estradiol plus tamoxifen, tamoxifen alone, estradiol plus fulvestrant, or fulvestrant alone. Apoptosis was detected by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Protein expression was assessed by western blot analysis. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction. All statistical tests were two-sided. MCF-7E2 tumor growth was stimulated by estradiol (cross-sectional area at week 13 = 1.06 cm2, 95% confidence interval [CI] = 0.82 to 1.30 cm2; Pestradiol-induced regression to 0.18 cm2 (95% CI = 0.15 to 0.21 cm2; P<.001), and tamoxifen or estradiol plus fulvestrant enhanced tumor growth to 1.00 cm2 (95% CI = 0.88 to 1.22 cm2). Estradiol increased the number of apoptotic cells in tumors by 23% (95% CI = 20% to 26%; P<.001) compared with all other treatments, decreased estrogen receptor alpha(ERalpha) protein expression, increased the expression of Fas mRNA and protein, decreased the expression of HER2/neu mRNA and protein and nuclear factor kappaB (NF-kappaB) protein but did not affect Fas ligand protein expression compared with control. Paradoxically, fulvestrant reversed this effect and stimulated MCF-7TAMLT tumor growth apparently through ERalpha-mediated regulation of Fas, HER2/neu, and NF-kappaB. Physiologic levels of estradiol induced regression of tamoxifen-stimulated breast cancer tumors, apparently by inducing the death receptor Fas and suppressing the antiapoptotic

Tamoxifen therapy for the management of pubertal gynecomastia: a systematic review

NARCIS (Netherlands)

Lapid, Oren; van Wingerden, Jan J.; Perlemuter, Leon

2013-01-01

Objective: A systematic review to assess the efficacy of tamoxifen in the management of idiopathic pubertal gynecomastia. Data sources: Searches were conducted using the databases of Medline (search engine PubMed) and Web of Science (R). Study selection: Studies reporting the use of Tamoxifen for

Spectral domain optical coherence tomography findings in tamoxifen retinopathy--a case report.

Science.gov (United States)

Nair, Sandhya Narayanan; Anantharaman, Giridhar; Gopalakrishnan, Mahesh; Vyas, Jyothiprakash

2013-01-01

To report spectral domain optical coherence tomography findings in a case of typical tamoxifen retinopathy. In this observational case report, a patient with tamoxifen retinopathy was imaged with spectral domain optical coherence tomography and fundus auto fluorescence. Spectral domain optical coherence tomography showed numerous hyperreflective spots within the retina, mainly in the inner retinal layers in both the eyes. The external limiting membrane, the Inner Segment-Outer Segment junction, and the photoreceptors were not discernable at the fovea in the right eye. In the left eye, there was foveal atrophy with total loss of photoreceptors. The autofluorescent images showed macular hypofluorescence with foveal hyperfluorescence. Spectral domain optical coherence tomography demonstrated abnormalities in the outer retinal layers in tamoxifen retinopathy. There were also characteristic alterations in the autofluorescence pattern at the macula in tamoxifen retinopathy.

A misdiagnosed Riedel's thyroiditis successfully treated by thyroidectomy and tamoxifen.

Science.gov (United States)

Wang, Chih-Jung; Wu, Ta-Jen; Lee, Chung-Ta; Huang, Shih-Ming

2012-12-01

Riedel's thyroiditis, known as invasive fibrous thyroiditis, is a very rare form of chronic thyroiditis. It is hard to make the diagnosis without surgical biopsy. We present a case of Riedel's thyroiditis in a 52-year-old female with past history of Hashimoto's thyroiditis. She suffered from bilateral neck pain, which radiated to both lower jaws. The erythrocyte sedimentation rate was 125 mm/hour. Subacute thyroiditis superimposed on Hashimoto's thyroiditis was diagnosed and treated with steroid. However the response was poor and she had a history of severe peptic ulcer. To avoid inducing the peptic ulcer by steroid, she received bilateral subtotal thyroidectomy. During surgery, the thyroid had severe adhesion to surrounding soft tissue and the pathology showed Riedel's thyroiditis. The neck pain improved after thyroidectomy. Tamoxifen has been given for 8 months and the size of remnant thyroid decreased to 8 mm. We concluded that combined thyroidectomy and tamoxifen successfully cured a patient with Riedel's thyroiditis. Copyright © 2012. Published by Elsevier B.V.

Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice

Energy Technology Data Exchange (ETDEWEB)

Hesselbarth, Nico; Pettinelli, Chiara [Department of Medicine, University of Leipzig, D-04103 Leipzig (Germany); Gericke, Martin [Institute of Anatomy, University of Leipzig, D-04103 Leipzig (Germany); Berger, Claudia [IFB Adiposity Disease, Core Unit Animal Models, University of Leipzig, D-04103 Leipzig (Germany); Kunath, Anne [German Center for Diabetes Research (DZD), Leipzig (Germany); Stumvoll, Michael; Blüher, Matthias [Department of Medicine, University of Leipzig, D-04103 Leipzig (Germany); Klöting, Nora, E-mail: nora.kloeting@medizin.uni-leipzig.de [IFB Adiposity Disease, Core Unit Animal Models, University of Leipzig, D-04103 Leipzig (Germany)

2015-08-28

Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects. - Highlights: • Tamoxifen treatment causes significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations. • Tamoxifen induces browning of subcutaneous AT and increased UCP-1 expression. • Tamoxifen changes adipocyte size distribution, and transient body composition.

Poly(amidoamine-Cholesterol Conjugate Nanoparticles Obtained by Electrospraying as Novel Tamoxifen Delivery System

Directory of Open Access Journals (Sweden)

R. Cavalli

2011-01-01

Full Text Available A new poly(amidoamine-cholesterol (PAA-cholesterol conjugate was synthesized, characterized and used to produce nanoparticles by the electrospraying technique. The electrospraying is a method of liquid atomization that consists in the dispersion of a solution into small charged droplets by an electric field. Tuning the electrospraying process parameters spherical PAA-chol nanoparticles formed. The PAA-cholesterol nanoparticles showed sizes lower than 500 nm and spherical shape. The drug incorporation capacity was investigated using tamoxifen, a lipophilic anticancer drug, as model drug. The incorporation of the tamoxifen did not affect the shape and sizes of nanoparticles showing a drug loading of 40%. Tamoxifen-loaded nanoparticles exhibited a higher dose-dependent cytotoxicity than free tamoxifen, while blank nanoparticles did not show any cytotoxic effect at the same concentrations. The electrospray technique might be proposed to produce tamoxifen-loaded PAA-chol nanoparticle in powder form without any excipient in a single step.

The effect of postoperative radiotherapy on leukocyte zinc, serum trace elements and nutritional status of breast cancer patients

International Nuclear Information System (INIS)

Antila, H.M.J.; Salo, M.S.; Kirvelae, O.; Nikkanen, V.

1992-01-01

Mononuclear (MNC) and polymorphonuclear cell (PMNC) zinc content was determined together with serum zinc, copper, selenium and iron concentrations in 24 operable breast cancer patients during and after postoperative radiotherapy. Anthropometric and biochemical indices of nutritional status were measured as background data. The measurements were carried out in the years 1987-1988. Nine patients used unconventional multivitamin or trace element preparations. A steady but statistically insignificant decrease in PMNC zinc was seen during treatment. No changes occurred in MNC zinc. Serum copper levels increased in five patients possibly due to tamoxifen treatment, but no other alterations occurred in serum trace element levels. Appetite was well maintained and nutritional status remained unaltered. Postoperative radiotherapy for breast carcinoma had thus no effect on either trace element or nutritional status. Patient-initiated alternative treatments did not significantly affect their trace element levels. This was probably due to small supplementation doses or irregular use of the preparations. (orig.)

The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

Science.gov (United States)

Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

2017-11-01

Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic aneurysms.

Science.gov (United States)

Grigoryants, Vladimir; Hannawa, Kevin K; Pearce, Charles G; Sinha, Indranil; Roelofs, Karen J; Ailawadi, Gorav; Deatrick, Kristopher B; Woodrum, Derek T; Cho, Brenda S; Henke, Peter K; Stanley, James C; Eagleton, Matthew J; Upchurch, Gilbert R

2005-01-01

Selective estrogen receptor modulators (SERMs), similar to estrogens, possess vasoprotective effects by reducing release of reactive oxygen species. Little is known about the potential effects of SERMs on the pathogenesis of abdominal aortic aneurysms (AAAs). This study's objective was to investigate the growth of experimental AAAs in the setting of the SERM tamoxifen. In the first set of experiments, adult male rats underwent subcutaneous tamoxifen pellet (delivering 10 mg/kg/day) implantation (n = 14) or sham operation (n = 16). Seven days later, all animals underwent pancreatic elastase perfusion of the abdominal aorta. Aortic diameters were determined at that time, and aortas were harvested 7 and 14 days after elastase perfusion for immunohistochemistry, real-time polymerase chain reaction, Western blot analysis, and zymography. In the second set of experiments, a direct irreversible catalase inhibitor, 3-amino-1,2,4-triazole (AT), was administered intraperitoneally (1 mg/kg) daily to tamoxifen-treated (n = 6) and control rats (n = 6), starting on day 7 after elastase perfusion. Aortic diameters were measured on day 14. In a third set of experiments, rats were perfused with catalase (150 mg/kg) after the elastase (n = 5), followed by daily intravenous injections of catalase (150 mg/kg/day) administered for 10 days. A control group of rats (n = 7) received 0.9% NaCl instead of catalase. Mean AAA diameters were approximately 50% smaller in tamoxifen-treated rats compared with sham rats 14 days after elastase perfusion (P = .002). The tamoxifen-treated group's aortas had a five-fold increase in catalase mRNA expression (P = .02) on day 7 and an eight-fold increase in catalase protein on day 14 (P = .04). Matrix metalloprotroteinase-9 activity was 2.4-fold higher (P = .01) on day 7 in the aortas of the controls compared to the tamoxifen-treated group's aortas. Tamoxifen-treated rats had approximately 40% fewer aortic polymorphonuclear neutrophils compared to

Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

DEFF Research Database (Denmark)

Joshi, Tejal; Elias, Daniel; Stenvang, Jan

2016-01-01

and 14-3-3 family genes. Integrating the inferred miRNA-target relationships, we investigated the functional importance of 2 central genes, SNAI2 and FYN, which showed increased expression in TamR cells, while their corresponding regulatory miRNA were downregulated. Using specific chemical inhibitors......Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA......-mediated gene regulation in three clinically-relevant tamoxifen-resistant breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all Tam...

Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

Science.gov (United States)

Nuzzo, F; Gallo, C; Lastoria, S; Di Maio, M; Piccirillo, M C; Gravina, A; Landi, G; Rossi, E; Pacilio, C; Labonia, V; Di Rella, F; Bartiromo, A; Buonfanti, G; De Feo, G; Esposito, G; D'Aniello, R; Maiolino, P; Signoriello, S; De Maio, E; Tinessa, V; Colantuoni, G; De Laurentiis, M; D'Aiuto, M; Di Bonito, M; Botti, G; Giordano, P; Daniele, G; Morabito, A; Normanno, N; de Matteis, A; Perrone, F

2012-08-01

To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

The effects of soy and tamoxifen on apoptosis in the hippocampus and dentate gyrus in a pentylenetetrazole-induced seizure model of ovariectomized rats.

Science.gov (United States)

Ebrahimzadeh-Bideskan, Ali Reza; Mansouri, Somaieh; Ataei, Mariam Lale; Jahanshahi, Mehrdad; Hosseini, Mahmoud

2018-03-01

The effects of tamoxifen and soy on apoptosis of the hippocampus and dentate gyrus of ovariectomized rats after repeated seizures were investigated. Female rats were divided into: (1) Control, (2) Sham, (3) Sham-Tamoxifen (Sham-T), (4) Ovariectomized (OVX), (5) OVX-Tamoxifen (OVX-T), (6)OVX-Soy(OVX-S) and (7) OVX-S-T. The animals in the OVX-S, OVX-T and OVX-S-T groups received soy extract (60 mg/kg; i.p.), tamoxifen (10 mg/kg) or both for 2 weeks before induction of seizures. The animals in these groups additionally received the mentioned treatments before each injection of pentylenetetrazole (PTZ; 40 mg/kg) for 6 days. The animals in the Sham and OVX groups received a vehicle of tamoxifen and soy. A significant decrease in the seizure score and TUNEL-positive neurons was seen in the OVX group compared to the Sham (P < 0.001). The animals in both the OVX-T and OVX-S groups had a significantly higher seizure score as well as number of TUNEL-positive neurons compared to the OVX group (P < 0.01-P < 0.001). Co-treatment of the OVX rats by the extract and tamoxifen decreased the seizure score and number of TUNEL-positive neurons compared to OVX-S (P < 0.001). Treatment of the OVX rats by either soy or tamoxifen increased the seizure score as well as the number of TUNEL-positive neurons in the hippocampal formation. Co-administration of tamoxifen and soy extract inhibited the effects of the soy extract and tamoxifen when they were administered alone. It might be suggested that both soy and tamoxifen have agonistic effects on estrogen receptors by changing the seizure severity.

Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

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Rukiye Yavaşer

2016-08-01

Full Text Available The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

Tamoxifen-independent recombination in the RIP-CreER mouse.

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Yanmei Liu

Full Text Available BACKGROUND: The inducible Cre-lox system is a valuable tool to study gene function in a spatial and time restricted fashion in mouse models. This strategy relies on the limited background activity of the modified Cre recombinase (CreER in the absence of its inducer, the competitive estrogen receptor ligand, tamoxifen. The RIP-CreER mouse (Tg (Ins2-cre/Esr1 1Dam is among the few available β-cell specific CreER mouse lines and thus it has been often used to manipulate gene expression in the insulin-producing cells of the endocrine pancreas. PRINCIPAL FINDINGS: Here, we report the detection of tamoxifen-independent Cre activity as early as 2 months of age in RIP-CreER mice crossed with three distinct reporter strains. SIGNIFICANCE: Evidence of Cre-mediated recombination of floxed alleles even in the absence of tamoxifen administration should warrant cautious use of this mouse for the study of pancreatic β-cells.

Thrombosis of digital arteries associated with tamoxifen use: case report.

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Hutchison, Richard L; Rayan, Ghazi M

2012-02-01

Arterial thrombosis in the upper extremity occurs often at the wrist. We report a unique case of thrombosis that involved multiple digital arteries, without radial or ulnar artery involvement, which developed only after using tamoxifen despite chronic occupational blunt percussive hand use. Revascularization was achieved after thrombectomy. Multiple digital arterial thromboses may complicate the use of tamoxifen. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

National Prociency Testing Result of CYP2D6*10 Genotyping for Adjuvant Tamoxifen Therapy in China.

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Guigao Lin

Full Text Available Tamoxifen has been successfully used for treating breast cancer and preventing cancer recurrence. Cytochrome P450 2D6 (CYP2D6 plays a key role in the process of metabolizing tamoxifen to its active moiety, endoxifen. Patients with variants of the CYP2D6 gene may not receive the full benefit of tamoxifen treatment. The CYP2D6*10 variant (the most common variant in Asians was analyzed to optimize the prescription of tamoxifen in China. To ensure referring clinicians have accurate information for genotype-guided tamoxifen treatment, the Chinese National Center for Clinical Laboratories (NCCL organized a national proficiency testing (PT to evaluate the performance of laboratories providing CYP2D6*10 genotyping. Ten genomic DNA samples with CYP2D6 wild-type or CYP2D6*10 variants were validated by PCR-sequencing and sent to 28 participant laboratories. The genotyping results and pharmacogenomic test reports were submitted and evaluated by NCCL experts. Additional information regarding the number of samples tested, the accreditation/certification status, and detecting technology was also requested. Thirty-one data sets were received, with a corresponding analytical sensitivity of 98.2% (548/558 challenges; 95% confidence interval: 96.7-99.1% and an analytic specificity of 96.5% (675/682; 95% confidence interval: 97.9-99.5%. Overall, 25/28 participants correctly identified CYP2D6*10 status in 10 samples; however, two laboratories made serious genotyping errors. Most of the essential information was included in the 20 submitted CYP2D6*10 test reports. The majority of Chinese laboratories are reliable for detecting the CYP2D6*10 variant; however, several issues revealed in this study underline the importance of PT schemes in continued external assessment and provision of guidelines.

CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer

DEFF Research Database (Denmark)

Regan, Meredith M; Leyland-Jones, Brian; Bouzyk, Mark

2012-01-01

Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer. Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. In this study, we investigated...

Risk of skin cancer following tamoxifen treatment in more than 16,000 breast cancer patients

DEFF Research Database (Denmark)

Præstegaard, Camilla; Kjaer, Susanne K.; Andersson, Michael

2016-01-01

Background: Women with breast cancer are at increased risk of developing skin cancer. Little is known about how tamoxifen affects this risk. We aimed to investigate whether tamoxifen treatment following breast cancer is associated with skin cancer. Methods: A cohort consisting of 44,589 women...... diagnosed with breast cancer during 1977–2007 from the nationwide clinical database of the Danish Breast Cancer Cooperative Group, was followed for a primary skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or melanoma] in the Danish Cancer Registry supplemented by data on BCC and SCC...... from the Danish Pathology Register. We investigated incidence of skin cancer among 16,214 women treated with tamoxifen compared to 28,375 women not treated with tamoxifen by calculating incidence rate ratios (IRRs) in Cox regression models. Results: Tamoxifen users were followed for a median of 2...

Brain Function, Structure, and Neurochemistry After Tamoxifen/Chemotherapy Assessed by Neuropsychologic Testing and H Magnetic Resonance Spectroscopy

National Research Council Canada - National Science Library

Ernst, Thomas

2000-01-01

...). On magnetic resonance spectroscopy (1H MRS), women who received tamoxifen (average 4.4 years) had no statistically significant differences in brain metabolite ratios compared to the negative control group...

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial.

Science.gov (United States)

Forbes, John F; Sestak, Ivana; Howell, Anthony; Bonanni, Bernardo; Bundred, Nigel; Levy, Christelle; von Minckwitz, Gunter; Eiermann, Wolfgang; Neven, Patrick; Stierer, Michael; Holcombe, Chris; Coleman, Robert E; Jones, Louise; Ellis, Ian; Cuzick, Jack

2016-02-27

Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6-8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64-1·23]). The non-inferiority of anastrozole was established (upper 95% CI

Functional screen for genes responsible for tamoxifen resistance in human breast cancer cells

NARCIS (Netherlands)

Meijer, Danielle; van Agthoven, Ton; Bosma, Peter T.; Nooter, Kees; Dorssers, Lambert C. J.

2006-01-01

Antiestrogens, such as tamoxifen, are widely used for endocrine treatment of estrogen receptor-positive breast cancer. However, as breast cancer progresses, development of tamoxifen resistance is inevitable. The mechanisms underlying this resistance are not well understood. To identify genes

Cancer Care Coordinators to Improve Tamoxifen Persistence in Breast Cancer: How Heterogeneity in Baseline Prognosis Impacts on Cost-Effectiveness.

Science.gov (United States)

Nair, Nisha; Kvizhinadze, Giorgi; Blakely, Tony

2016-12-01

To assess the cost-effectiveness of a cancer care coordinator (CCC) in helping women with estrogen receptor positive (ER+) early breast cancer persist with tamoxifen for 5 years. We investigated the cost-effectiveness of a CCC across eight breast cancer subtypes, defined by progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and local/regional spread. These subtypes range from excellent to poorer prognoses. The CCC helped in improving tamoxifen persistence by providing information, checking-in by phone, and "troubleshooting" concerns. We constructed a Markov macrosimulation model to estimate health gain (in quality-adjusted life-years or QALYs) and health system costs in New Zealand, compared with no CCC. Participants were modeled until death or till the age of 110 years. Some input parameters (e.g., the impact of a CCC on tamoxifen persistence) had sparse evidence. Therefore, we used estimates with generous uncertainty and conducted sensitivity analyses. The cost-effectiveness of a CCC for regional ER+/PR-/HER2+ breast cancer (worst prognosis) was NZ $23,400 (US $15,800) per QALY gained, compared with NZ $368,500 (US $248,800) for local ER+/PR+/HER2- breast cancer (best prognosis). Using a cost-effectiveness threshold of NZ $45,000 (US $30,400) per QALY, a CCC would be cost-effective only in the four subtypes with the worst prognoses. There is value in investigating cost-effectiveness by different subtypes within a disease. In this example of breast cancer, the poorer the prognosis, the greater the health gains from a CCC and the better the cost-effectiveness. Incorporating heterogeneity in a cost-utility analysis is important and can inform resource allocation decisions. It is also feasible to undertake in practice. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

The role of the expression of bcl-2, p53 gene in tamoxifen-induced apoptosis of breast cancer cells and its relationship with hormone receptor status

Energy Technology Data Exchange (ETDEWEB)

Noh, Woo Chul; Ham, Yong Ho [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1998-01-01

To investigate the relationship of bcl-2, p53, ER and tamoxifen-induced apoptosis of breast cancer cells, MCF-7 (ER+/bcl-2+/p53-) and MB MDA 468 (ER-/bcl-2-/p53+) cell line were cultured in estrogen-free condition. E2(10`-`9M) and tamoxifen (10`-`5M) were added to the media. The changes of bcl-2 and mutant p53 protein were checked by Western blot and apoptosis were measured by flowcytometry. In MCF-7 cells, we found that treatment with tamoxifen resulted in a decrease in bcl-2 protein level, but produced no change in mutant p53. In MB MDA 468 cell however, there were no changes of bcl-2 and mutant p53 protein level when E2 or tamoxifen were added. Apoptotic cells increased with time-dependent pattern when tamoxifen was added to MCF-7 cells. According to these result, ER+/blc-2+/mutant p53- cells, when treated with tamoxifen, were converted into bcl-2/mutant p53- cells which were more prone to apoptosis than bcl-2-/mutant p53+ cells. The paradoxical correlation of bcl-2 and ER which had been observed in clinical studies might be explained with this results and bcl-2 protein seems to be one of important factors that can predict the effect of hormone therapy. (author). 26 refs., 5 figs

The role of the expression of bcl-2, p53 gene in tamoxifen-induced apoptosis of breast cancer cells and its relationship with hormone receptor status

International Nuclear Information System (INIS)

Noh, Woo Chul; Ham, Yong Ho

1998-01-01

To investigate the relationship of bcl-2, p53, ER and tamoxifen-induced apoptosis of breast cancer cells, MCF-7 (ER+/bcl-2+/p53-) and MB MDA 468 (ER-/bcl-2-/p53+) cell line were cultured in estrogen-free condition. E2(10'-'9M) and tamoxifen (10'-'5M) were added to the media. The changes of bcl-2 and mutant p53 protein were checked by Western blot and apoptosis were measured by flowcytometry. In MCF-7 cells, we found that treatment with tamoxifen resulted in a decrease in bcl-2 protein level, but produced no change in mutant p53. In MB MDA 468 cell however, there were no changes of bcl-2 and mutant p53 protein level when E2 or tamoxifen were added. Apoptotic cells increased with time-dependent pattern when tamoxifen was added to MCF-7 cells. According to these result, ER+/blc-2+/mutant p53- cells, when treated with tamoxifen, were converted into bcl-2/mutant p53- cells which were more prone to apoptosis than bcl-2-/mutant p53+ cells. The paradoxical correlation of bcl-2 and ER which had been observed in clinical studies might be explained with this results and bcl-2 protein seems to be one of important factors that can predict the effect of hormone therapy. (author). 26 refs., 5 figs

Tamoxifen-Containing Eye Drops Successfully Trigger Cre-Mediated Recombination in the Entire Eye.

Science.gov (United States)

Schlecht, Anja; Leimbeck, Sarah V; Tamm, Ernst R; Braunger, Barbara M

2016-01-01

Embryonic lethality in mice with targeted gene deletion is a major issue that can be circumvented by using Cre-loxP-based animal models. Various inducible Cre systems are available, e.g. such that are activated following tamoxifen treatment, and allow deletion of a specific target gene at any desired time point during the life span of the animal. In this study, we describe the efficiency of topical tamoxifen administration by eye drops using a Cre- reporter mouse strain (R26R). We report that tamoxifen-responsive CAGGCre-ER (TM) mice show a robust Cre- mediated recombination throughout the entire eye.

Phase I Clinical Trial Assessing Temozolomide and Tamoxifen With Concomitant Radiotherapy for Treatment of High-Grade Glioma

International Nuclear Information System (INIS)

Patel, Shilpen; DiBiase, Steven; Meisenberg, Barry; Flannery, Todd; Patel, Ashish; Dhople, Anil; Cheston, Sally; Amin, Pradip

2012-01-01

Purpose: The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. Methods and Materials: A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were given tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status ≥60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m 2 divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m 2 increments until the MTD was reached. When ≥2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m 2 . A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. Results: A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m 2 . One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m 2 . Conclusions: The MTD of tamoxifen was 100 mg/m 2 when given concurrently with temozolomide 75 mg/m 2 and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.

Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

Directory of Open Access Journals (Sweden)

John Koren

Full Text Available MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB. Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

Persistent tumor-induced osteomalacia confirmed by elevated postoperative levels of serum fibroblast growth factor-23 and 5-year follow-up of bone density changes.

Science.gov (United States)

Zimering, Mark B; Caldarella, Felice A; White, Kenneth E; Econs, Michael J

2005-01-01

To describe a case of persistent tumor-induced osteomalacia, determine whether serum fibroblast growth factor-23 (FGF-23) levels postoperatively indicate incomplete tumor resection, and report lumbar spine and forearm bone mineral density (BMD) changes during 5 years of follow-up. We present clinical, radiologic, histologic, and bone densitometry data as well as serum FGF-23 levels (determined with use of a novel C-terminal enzyme-linked immunosorbent assay) from the study patient and discuss these findings in the context of previous literature. A 52-year-old man, who presented with muscle weakness and multiple fractures, was found to have low values for serum phosphorus, serum 1,25-dihydroxyvitamin D, and maximal tubular reabsorption of phosphate per glomerular filtration rate, a high level of serum alkaline phosphatase, and a normal serum concentration of parathyroid hormone, characteristic of tumor-induced osteomalacia. Magnetic resonance imaging to evaluate an abnormality of the left foot revealed a soft tissue mass, biopsy of which confirmed the presence of a benign, phosphaturic, mesenchymal tumor. The baseline serum FGF-23 level (2,050 RU/mL) was more than 17 times the upper limit of normal for adults (23 to 118 RU/mL) and decreased substantially within 1 day after partial resection of the tumor but remained above normal postoperatively. BMD changes indicated rapid substantial recovery of vertebral BMD but ongoing loss of forearm bone density. The serum FGF-23 level is high in a substantial proportion of patients with tumor-induced osteomalacia. The postoperative above normal levels of serum FGF-23 correlated with known persistence of tumor in our study patient. In a patient with normal renal function, such as our study patient, levels of serum FGF-23 studied with use of the C-terminal enzyme-linked immunosorbent assay reached their nadir within 24 hours postoperatively. This result suggests that this assay can provide clinicians with rapid prognostic

Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Science.gov (United States)

Rossi, Emanuela; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; D'Aiuto, Massimiliano; Rinaldo, Massimo; Botti, Gerardo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2008-01-10

To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients

International Nuclear Information System (INIS)

Wegman, Pia; Vainikka, Linda; Stål, Olle; Nordenskjöld, Bo; Skoog, Lambert; Rutqvist, Lars-Erik; Wingren, Sten

2005-01-01

Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy. The patients were genotyped using PCR followed by cleavage with restriction enzymes. Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11–0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21–1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19–0.74, P = 0.0041). The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort

Lack of evidence from HPLC 32P-post-labelling for tamoxifen-DNA adducts in the human endometrium.

Science.gov (United States)

Carmichael, P L; Sardar, S; Crooks, N; Neven, P; Van Hoof, I; Ugwumadu, A; Bourne, T; Tomas, E; Hellberg, P; Hewer, A J; Phillips, D H

1999-02-01

Tamoxifen is associated with an increased incidence of endometrial cancer in women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts in this tissue. A previous study exploring DNA adducts in human endometria, utilizing thin layer chromatography 32P-postlabelling, found no evidence for adducts in tamoxifen-treated women [Carmichael,P.L., Ugwumadu,A.H.N., Neven,P., Hewer,A.J., Poon,G.K. and Phillips,D.H. (1996) Cancer Res., 56, 1475-1479]. However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K., Ranjaniemi,H., Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374-4377] suggested that very low levels could be detected. We have sought to investigate this question further by reproducing the HPLC methodology at two centres, and analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isolated from tamoxifen-treated rats was used as a positive control. We found no convincing evidence for tamoxifen-derived DNA adducts in human endometrium. HPLC elution profiles of post-labelled DNA from tamoxifen-treated women were indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.

Tamoxifen and CYP2D6

DEFF Research Database (Denmark)

Cronin-Fenton, Deirdre P.; Damkier, Per

2018-01-01

Tamoxifen reduces the rate of breast cancer recurrence by about one-half. It is converted to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6) and transported by ATP-binding cassette transporters. Genetic polymorphisms that confer reduced CYP2...

Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

International Nuclear Information System (INIS)

Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S.

2007-01-01

Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17β-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca 2+ delaying the opening of the permeability transition pore. The presence of 25 μM E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H 2 O 2 in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered

Identification of a putative protein-profile associating with tamoxifen therapy-resistance in breast cancer

NARCIS (Netherlands)

A. Umar (Arzu); J.W.M. Martens (John); J.A. Foekens (John); L. Paša-Tolić (Ljiljana); H. Kang; A.M. Timmermans (Mieke); M.P. Look (Maxime); M.E. Meijer van Gelder (Marion); N. Jaitly (Navdeep); M.A. den Bakker (Michael)

2009-01-01

textabstractTamoxifen-resistance is a major cause of death in patients with recurrent breast cancer. Current clinical parameters can correctly predict therapy response in only half of the treated patients. Identification of proteins that associate with tamoxifen-resistance is a first step towards

Approaches for predicting effects of unintended environmental exposure to an endocrine active pharmaceutical, tamoxifen

Science.gov (United States)

Tamoxifen is an endocrine-active pharmaceutical (EAP) that is used world-wide. Because tamoxifen is a ubiquitous pharmaceutical and interacts with estrogen receptors, a case study was conducted with this compound to (1) determine effects on reproductive endpoints in a nontarget s...

Tamoxifen and the Rafoxifene analog LY117018: their effects on arachidonic acid release from cells in culture and on prostaglandin I2 production by rat liver cells

International Nuclear Information System (INIS)

Levine, Lawrence

2004-01-01

Tamoxifen is being used successfully to treat breast cancer. However, tamoxifen also increases the risk of developing endometrial cancer in postmenopausal women. Raloxifene also decreases breast cancer in women at high risk and may have a lower risk at developing cancer of the uterus. Tamoxifen has been shown to stimulate arachidonic acid release from rat liver cells. I have postulated that arachidonic acid release from cells may be associated with cancer chemoprevention. Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [ 3 H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I 2 produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. Tamoxifen is about 5 times more effective than LY117018 at releasing arachidonic acid from all the cells tested. In rat liver cells only tamoxifen stimulates basal prostaglandin I 2 production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I 2 production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. Tamoxifen and the raloxifene analog, LY117018, may prevent estrogen-independent as well as estrogen-dependent breast cancer by stimulating phospholipase activity and initiating arachidonic acid release. The release of arachidonic acid and/or molecular reactions that accompany that release may initiate pathways that prevent tumor growth. Oxygenation of the intracellularly released arachidonic acid and its metabolic products may mediate some of the pharmacological actions of tamoxifen and raloxifene

Effects of 13- cis-retinoic acid on the tamoxifen induced uterine histological changes in the rabbit

International Nuclear Information System (INIS)

Hamid, S.; Minhas, L.A.; Khan, M.Y.

2013-01-01

Objective: To study the effects of 13-cis-retinoic acid on the tamoxifen induced uterine histological changes in the rabbit. Study Design: Experimental - randomized controlled trial. Place and Duration of study: The study was conducted for 4 months at the department of Anatomy, Army Medical College and National Institute of Health in 2007. Material and Methods: The animals were randomly divided into three groups, a control group A, and two experimental groups B and C, consisting of thirty rabbits each. The experimental groups were treated with tamoxifen only and tamoxifen plus retinoic acid, respectively. The animals were sacrificed after three months. The uteri were then processed for paraffin embedding. Sections were then assessed for the luminal epithelial height, endometrial area and percentage of mitotic figures. Results: The results obtained were suggestive of uterine proliferation by tamoxifen. The adjuvant administration of 13-cis-retinoic acid produced a statistically significant (p = 0.002) inhibitory effect on the tamoxifen induced increase in the area of endometrium, whereas no significant suppressive effect of this drug has been observed on the other parameters when compared with Group B. Conclusion: 13-cis Retinoic acid has not shown a significant role in the reversal of tamoxifen induced changes in the uterine tissue after a short term administration of three months. (author)

Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells.

Science.gov (United States)

Kim, Sangmin; Lee, Jeongmin; Oh, Soo Jin; Nam, Seok Jin; Lee, Jeong Eon

2015-09-01

Although tamoxifen is the most common and effective therapy for treatment of estrogen receptor-α (ER-α) breast cancer patients, resistance of endocrine therapy occurs, either de novo or acquired during therapy. Here, we investigated the clinical value of epidermal growth factor receptor (EGFR) in tamoxifen-resistant (TamR) patients and the differential effect of EGFR inhibitors, neratinib and gefitinib, on TamR breast cancer cell model. The morphology of TamR MCF7 cells showed mesenchymal phenotypes and did not induce cell death by tamoxifen treatment compared with tamoxifen‑sensitive (TamS) MCF7 cells. In addition, mesenchymal marker proteins, including N-cadherin (N-cad), fibronectin (FN), and Slug, significantly increased in TamR cells. In contrast, ER-α and E-cadherin (E-cad) were greatly decreased. We also found that the levels of EGFR and HER2 expression were increased in TamR cells. Furthermore, we observed that EGFR expression was directly involved with poor prognosis of tamoxifen-treated breast cancer patients using the GSE1378 date set. Thus, we treated TamR and TamS cells with EGFR inhibitors, neratinib and gefitinib, respectively. Interestingly, neratinib induced apoptotic cell death of TamR but not gefitinib. Cleaved PARP-1 expression was also increased by neratinib treatment in TamR cells. Therefore, we suggest that neratinib may be a potential therapeutic drug for treating TamR breast cancer.

Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

Science.gov (United States)

Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

2017-05-02

Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

Post-operative megavoltage irradiation of minor salivary gland malignancies - 30 year follow-up

International Nuclear Information System (INIS)

Birdwell, Sandra H.; Terris, David J.; Fee, Willard E.; Goffinet, Don R.

1996-01-01

Purpose/Objective: To describe the clinical presentation, treatment techniques, outcome, and complications of a large single institutional experience with long-term follow-up after surgery and post-operative radiation therapy for the treatment of minor salivary gland malignancies. Materials and Methods: Fifty-five patients with minor salivary gland tumors were treated definitively between 1966 and 1995. Patients were staged using the 1992 AJCC staging system according to the anatomic site of origin. Follow-up averaged 7.2 years. The mean age at treatment was 54 years. There were 35 men and 20 women. Thirty patients had involved surgical margins and 25 had negative surgical margins. All patients were treated with 4-6 MeV linear accelerators. Radiation techniques included 3 field isocentric or opposed lateral pair techniques depending on the site of origin. The mean radiation dose was 60 Gy (range 50-70 Gy). Survival, both actuarial and relapse free, was determined from the treatment completion date using the method of Kaplan and Meier. Standard statistical tests (Gehan, Cox) were used to calculate the significance of covariates. Results: Minor salivary gland histologic diagnoses included 32 cases of adenoid cystic carcinoma, 15 adenocarcinomas, 7 mucoepidermoid carcinomas, and 1 pleomorphic adenoma. Eight patients had Stage I tumors, 13 had Stage II, another 13 had Stage III lesions, while 21 had Stage IV tumors (locally advanced but non-metastatic). Twenty-five tumors involved the nasal cavity-paranasal sinuses, 23 arose from the oral cavity, 5 from the oropharynx, and 2 from the glottis. Patients with adenoid cystic carcinomas had improved local control and overall survival compared with those with adenocarcinomas (p = 0.03, 0.02, respectively). Malignancies arising from the palate had improved local control rates compared with tumors arising from other anatomic sites (p = 0.04). Patients with Stage I and II disease had improved freedom from relapse compared with

Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

Energy Technology Data Exchange (ETDEWEB)

Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

2007-05-23

Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

Tamoxifen induces regression of estradiol-induced mammary cancer in the ACI.COP-Ept2 rat model.

Science.gov (United States)

Ruhlen, Rachel L; Willbrand, Dana M; Besch-Williford, Cynthia L; Ma, Lixin; Shull, James D; Sauter, Edward R

2009-10-01

The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5-7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonance imaging, by 89%. Tumors expressed estrogen receptors (ER), progesterone receptor (PR), and Erbb2. ERalpha and PR were overexpressed in tumor compared to adjacent non-tumor mammary gland. Thus, this model is highly relevant to hormone responsive human breast cancers.

Postoperative stiff shoulder after open rotator cuff repair: a 3- to 20-year follow-up study.

Science.gov (United States)

Vastamäki, H; Vastamäki, M

2014-12-01

Stiffness after a rotator cuff tear is common. So is stiffness after an arthroscopic rotator cuff repair. In the literature, however, postoperative restriction of passive range of motion after open rotator cuff repair in shoulders with free passive range of motion at surgery has seldom been recognized. We hypothesize that this postoperative stiffness is more frequent than recognized and slows the primary postoperative healing after a rotator cuff reconstruction. We wondered how common is postoperative restriction of both active and passive range of motion after open rotator cuff repair in shoulders with free passive preoperative range of motion, how it recovers, and whether this condition influences short- and long-term results of surgery. We also explored factors predicting postoperative shoulder stiffness. We retrospectively identified 103 postoperative stiff shoulders among 416 consecutive open rotator cuff repairs, evaluating incidence and duration of stiffness, short-term clinical results and long-term range of motion, pain relief, shoulder strength, and functional results 3-20 (mean 8.7) years after surgery in 56 patients. The incidence of postoperative shoulder stiffness was 20%. It delayed primary postoperative healing by 3-6 months and resolved during a mean 6.3 months postoperatively. External rotation resolved first, corresponding to that of the controls at 3 months; flexion and abduction took less than 1 year after surgery. The mean summarized range of motion (flexion + abduction + external rotation) increased as high as 93% of the controls' range of motion by 6 months and 100% by 1 year. Flexion, abduction, and internal rotation improved to the level of the contralateral shoulders as did pain, strength, and function. Age at surgery and condition of the biceps tendon were related to postoperative stiffness. Postoperative stiff shoulder after open rotator cuff repair is a common complication resolving in 6-12 months with good long-term results. © The

Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

Directory of Open Access Journals (Sweden)

Jennifer M Colón

2016-01-01

Full Text Available Spinal cord injury (SCI is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

Post-operative chemosensitized radiation with modulated 5-fluorouracil (5-FU) following resection of adenocarcinoma of the esophagus and esophagogastric (EG) junction

International Nuclear Information System (INIS)

Kurtzman, S.M.; Whittington, R.; Vaughn, D.; Rosato, E.F.; Haller, D.G.

1995-01-01

Purpose: To evaluate the survival and toxicity of post-operative chemosensitized radiation with modulated 5-FU chemotherapy in patients with resected adenocarcinomas of the esophagus and EG junction. Materials and Methods: One hundred and ninety-two patients with localized adenocarcinomas of the esophagus and EG junction were treated with single or combined modality therapy. The results in the first 165 patients treated between 1972 and 1989 demonstrated that survival was improved with chemosensitized radiation therapy following surgical resection. In the final group of patients treated between 1985 and 1989 a 96 hour inpatient 5-FU infusion was used to provide chemosensitization in those patients. Twenty-seven patients have been treated between January 1990 and December 1994 using a new outpatient regimen with modulated 5-FU chemotherapy for chemosensitization. Radiation and chemotherapy commenced within 6 weeks of surgery. The dose of radiation was 54 Gy in patients with no residual tumor, and 59.4 to 63.0 Gy in patients with positive margins or residual tumor. Modulated 5-FU using bolus 5-FU with Leukovorin +/-α-interferon (α-IFN) was given during the first and fifth week of radiation. Results: Median follow-up of surviving patients treated with modulated 5-FU is 15 months (max - 46 mos). Survival is 71% at 1 year, 45% at 2 years and 39% at 3 years. This compares favorably with the survival with 5-FU infusion, 75% - 1 year, 35% - 2 year, and 10% - 3 year. The toxicity of modulated 5-FU was no different from that observed in patients treated with 5-FU infusion. Three patients treated with modulated 5-FU leukovorin and α-IFN required intravenous hydration, and two patients experienced grade 3 leukopenia. There were two radiation related events in these patients, one case of radiation pneumonitis and one patient with pericarditis. Conclusions: Based on this experience, aggressive therapy of adenocarcinomas of the esophagus and EG junction with surgery and

A systematic review and methodological evaluation of published cost-effectiveness analyses of aromatase inhibitors versus tamoxifen in early stage breast cancer.

Directory of Open Access Journals (Sweden)

Ava A John-Baptiste

Full Text Available BACKGROUND: A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs. For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs of five years of aromatase inhibitors (AI versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS but not overall survival (OS and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. METHODS: We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY. We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. RESULTS: We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. CONCLUSION: Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs

Dextromethorphan as a phenotyping test to predict endoxifen exposure in patients on tamoxifen treatment

NARCIS (Netherlands)

Graan, A.J. de; Teunissen, S.F.; Vos, F.Y. de; Loos, W.J.; Schaik, R.H. van; Jongh, F.E. de; Vos, A.I. de; Alphen, R.J. van; Holt, B. van der; Verweij, J.; Seynaeve, C.; Beijnen, J.H.; Mathijssen, R.H.

2011-01-01

PURPOSE: Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the

Mitotically Active Leiomyoma of the Uterus in a Postmenopausal Breast Cancer Patient Receiving Tamoxifen

Directory of Open Access Journals (Sweden)

I-Feng Liu

2006-06-01

Conclusion: Endometrial cancer is rarely noted in breast cancer patients taking tamoxifen. Further, none have reported mitotically active leiomyoma of the uterus. From this case, endometrial proliferation and mitotically active leiomyoma of the uterus may be related to tamoxifen therapy, and should not be neglected in breast cancer patients.

Refractive surgery for accommodative esotropia: 5-year follow-up.

Science.gov (United States)

Magli, Adriano; Forte, Raimondo; Gallo, Flavio; Carelli, Roberta

2014-02-01

To assess the long-term effectiveness and safety of refractive surgery with LASIK or photorefractive keratectomy (PRK) for treating accommodative esotropia in adults. All patients with accommodative esotropia treated with LASIK or PRK until December 2007 and with a minimum follow-up of 5 years were retrospectively included. LASIK was performed on 44 eyes of 22 patients (12 women, 10 men; mean age: 22.7 ± 2.9 years). Mean postoperative follow-up was 62.1 ± 3.2 months. PRK was performed on 16 eyes of 8 patients (4 women, 4 men; mean age: 23.7 ± 1.7 years). Mean postoperative follow-up was 61.3 ± 2.8 months. At the 5-year follow-up, the mean cycloplegic refraction was more hyperopic in the PRK group (0.3 ± 0.8 vs 0.06 ± 0.3 diopters, P = .01). Correction of esotropia to esophoria or orthotropia was present in 21 patients (95.4%) treated with LASIK and in all patients treated with PRK. Both LASIK and PRK were effective in the long-term reduction of accommodative esotropia. Copyright 2014, SLACK Incorporated.

Toxicidade ocular causada pelo tamoxifeno: relato de caso Ocular toxicity caused by tamoxifen: case report

Directory of Open Access Journals (Sweden)

Eliane Terumi Inada

2005-08-01

Full Text Available O objetivo desse trabalho é relatar um caso de toxicidade ocular pelo tamoxifeno. Para isso, aferiu-se a melhor acuidade visual corrigida de ambos os olhos em tabela de Snellen. Foram realizados biomicroscopia do segmento anterior, refração, oftalmoscopia, angiofluoresceinografia e retinografia numa paciente de 63 anos, sexo feminino, cor branca, em uso de tamoxifeno 20 mg/dia há 4 anos, com acuidade visual corrigida de 20/70 e 20/40. A biomicroscopia do segmento anterior apresentava ceratopatia verticilata e catarata nuclear e cortical posterior de 1+/4 em ambos os olhos. À oftalmoscopia, foi verificado alteração do brilho macular de ambos os olhos. E a angiofluoresceinografia mostrou hiperfluorescência na área macular em fase precoce (defeito em janela. Relata-se um caso de ceratopatia e maculopatia causadas pelo tamoxifeno.To report tamoxifen ocular toxicity. The best visual acuity was measured in both eyes with Snellen chart, slit-lamp examination of anterior segment, refraction, dilated fundus examination, fluorescein angiography and retinography in a 63-year-old patient, female, white, using tamoxifen 20 mg/day for 4 years, with 20/70 and 20/40 corrected visual acuity. The anterior segment examination showed corneal linear subepithelial opacity inferior to the visual axis and nuclear and posterior cortical cataract (1+/4 in both eyes. Fundus examination showed alteration of macular color in both eyes. Fluorescein angiography presented hyperfluorescence in the macular area at an early phase (window defect. Report of keratopathy and maculopathy caused by tamoxifen.

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

International Nuclear Information System (INIS)

Fowble, B.; Fein, D.A.; Hanlon, A.L.; Eisenberg, B.L.; Hoffman, J.P.; Sigurdson, E.R.; Daly, M.B.; Goldstein, L.J.

1995-01-01

Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

Energy Technology Data Exchange (ETDEWEB)

Fowble, B; Fein, D A; Hanlon, A L; Eisenberg, B L; Hoffman, J P; Sigurdson, E R; Daly, M B; Goldstein, L J

1995-07-01

Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

The Effect of Tamoxifen Administration and γ-Irradiation on Thyroid Hormones Levels in Rats Bearing Mammary Tumours

International Nuclear Information System (INIS)

Abdelgawad, M.R.

2013-01-01

Breast Cancer is the most common malignancy among women in most developed and developing regions of the world, in female, tamoxifen acting as an oestrogen antagonist on the breast. Thyroid hormones can stimulate the proliferation in vitro of certain tumor cell lines. The aim of the present study is to evaluate the effect of tamoxifen and/ or irradiation treatment on thyroid hormones in rats' mammary tumours. Forty-two female Sprague-Dawely rats randomly divided into seven groups' proliferation (6 rats each). Control group, normal rats supplemented with tamoxifen for 3 weeks, normal rats exposed to a single dose 3Gy γ-rays, rats treated with Dimethylbenz (a) anthracene (DMBA) dissolved in corn oil (30ppm) sc and followed for 6 months until breast cancer occurrence, breast cancer bearing rats supplemented with tamoxifen for 3 weeks twice a day, breast cancer bearing rats exposed to a single dose 3Gy γ-rays, breast cancer bearing rats exposed to a single dose 3Gy γ-rays and supplemented with tamoxifen for 3 weeks twice a day. At the end of the experiment, mammary tumours and control rats were sacrificed after 3 weeks from different treatments and serum thyroid hormones and estradiol (E2) levels were assayed using commercial kits. Results show T4 and E2 levels not triiodothyronine (T3) were altered in different experimental groups. It could be concluded that γ-irradiation promote the expression of neoplastic potential by affecting both E2 and thyroid hormones and tamoxifen may alter the thyroid hormones. Tamoxifen administration and γ-irradiation may have worth effects on thyroxin (T4) and E2 levels. It is recommended to further studies towards the bystander effect of γ-rays exposure and tamoxifen treatment on the tissue culture and molecular biology scale.

FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells

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Lukasz Turczyk

2017-10-01

Full Text Available Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa. Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.

AIB1 is required for the acquisition of epithelial growth factor receptor-mediated tamoxifen resistance in breast cancer cells

International Nuclear Information System (INIS)

Zhao Wenhui; Zhang Qingyuan; Kang Xinmei; Jin Shi; Lou Changjie

2009-01-01

Acquired resistance to tamoxifen has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this condition has not been completely elucidated. In this study, a tamoxifen-resistant (Tam-R) MCF-7 breast cancer cell line was developed to mimic the occurrence of acquired tamoxifen resistance as seen in clinical practice. Increased expression levels of HER1, HER2 and the estrogen receptor (ER)-AIB1 complex were found in tamoxifen-resistant cells. EGF stimulation and gefitinib inhibition experiments further demonstrated that HER1/HER2 signaling and AIB1 were involved in the proliferation of cells that had acquired Tam resistance. However, when AIB1 was silenced with AIB1-siRNA in Tam-R cells, the cell growth stimulated by the HER1/HER2 signaling pathway was significantly reduced, and the cells were again found to be inhibited by tamoxifen. These results suggest that the AIB1 protein could be a limiting factor in the HER1/HER2-mediated hormone-independent growth of Tam-R cells. Thus, AIB1 may be a new therapeutic target, and the removal of AIB1 may decrease the crosstalk between ER and the HER1/HER2 pathway, resulting in the restoration of tamoxifen sensitivity in tamoxifen-resistant cells.

The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen

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Chen, Xingui; Tao, Longxiang; Li, Jingjing; Wu, Jiaonan; Zhu, Chunyan; Yu, Fengqiong; Zhang, Lei; Zhang, Jingjie; Qiu, Bensheng; Yu, Yongqiang; He, Xiaoxuan

2017-01-01

Abstract Background: Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment. Methods: A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region. Results: Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance. Conclusion: This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients. PMID:28177081

THE PROFILE OF TAMOXIFEN USER DUE TO GYNECOMASTIA INDUCED BY ANABOLIC STEROIDS FOR BODYBUILDERS OR BODYBUILDING

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E. Santos

2016-09-01

Full Text Available Due to valorization of body appearance, the seek for a good physic body gets a central importance in externalization of subjectivity and in the construction the identities of the people. Because of this, them invest time to look for devices to streamline results to get a perfect body, between mechanisms used there is the use of anabolic steroids (AS. With the rapid response this kind of treatment, there are aware concerns their side effects such as gynecomastia which is characterized by breast enlargement of man. In an attempt to prevent this effect aesthetically uncomfortable, the users seek take medicines such as tamoxifen to reverse or prevent this situation without proper prescription or monitoring of a pharmacist professional, as well as almost all treatments with EA which are made clandestinely. This work aimed to describe profile among consumers seeking the tamoxifen therapy to prevent or treat gynecomastia induced using EA. The target audience was composed of bodybuilders men that were making anabolic cycles, aiming fast muscular hypertrophy. Two questionnaires were applied, one to the drugstores that sell these drugs and one for bodybuilders who buy these drugs. Tamoxifen user profile found in this study shows that they are young people aged 18 to 35 years old, seeking muscle hypertrophy strength. As the natural results are slow, influenced by training friends, start using EA, even declaring know about the risks to health. Use along with these steroids, tamoxifen, in an attempt to prevent or treat gynecomastia, get the medication in drugstores without a prescription and without the pharmacist questioning, demonstrating that pharmaceutical care is still not fully deployed and functioning

Tamoxifen treatment and gynecologic side effects : A review

NARCIS (Netherlands)

Mourits, MJE; De Vries, EGE; Willemse, PHB; Ten Hoor, KA; Hollema, H; Van der Zee, AGJ

Objective: To review the literature on tamoxifen side effects on the female genital tract and psychosexual function in premenopausal and postmenopausal women. Data Sources: We used the English-language literature in MEDLINE and reference lists from selected articles. Search terms included:

Discrepancy between ultrasonography and hysteroscopy and histology of endometrium in postmenopausal breast cancer patients using tamoxifen

NARCIS (Netherlands)

Mourits, MJE; Van der Zee, AGJ; Willemse, PHB; Ten Hoor, KA; Hollema, H; De Vries, EGE

Background. The increased risk of endometrial carcinoma following the use of tamoxifen has stimulated studies on endometrial diagnostic screening methods. In tamoxifen users the endometrial thickening observed with transvaginal ultrasonography (TVU) frequently cannot be confirmed by hysteroscopy or

Tamoxifen enhances stemness and promotes metastasis of ERα36+ breast cancer by upregulating ALDH1A1 in cancer cells

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Wang, Qiang; Jiang, Jun; Ying, Guoguang; Xie, Xiao-Qing; Zhang, Xia; Xu, Wei; Zhang, Xuemin; Song, Erwei; Bu, Hong; Ping, Yi-Fang; Yao, Xiao-Hong; Wang, Bin; Xu, Shilei; Yan, Ze-Xuan; Tai, Yanhong; Hu, Baoquan; Qi, Xiaowei; Wang, Yan-Xia; He, Zhi-Cheng; Wang, Yan; Wang, Ji Ming; Cui, You-Hong; Chen, Feng; Meng, Kun; Wang, Zhaoyi; Bian, Xiu-Wu

2018-01-01

The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer. PMID:29393296

CYP2D6 polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study

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Wickramage I

2017-03-01

Full Text Available Ishani Wickramage,1 Kamani Hemamala Tennekoon,1 Merenchi Arachchige Yasantha Ariyaratne,2 Asanka Sudeshini Hewage,1 Tharmini Sundralingam,1 1Institute of Biochemistry, Molecular Biology and Biotechnology (IBMBB, University of Colombo, Colombo, Sri Lanka; 2National Cancer Institute, Maharagama, Sri Lanka Introduction and aims: Tamoxifen is an adjuvant drug effective in treating hormone ­receptor – positive breast cancer. However, 30%–50% of patients relapse and many develop adverse effects, such as hot flashes and fatty liver. Allelic variations altering the activity of cytochrome P450-2D6 enzyme affect response to tamoxifen by modulating metabolism of tamoxifen into its pharmacologically active metabolite endoxifen. Although association between CYP2D6 polymorphisms and recurrence of breast cancer in patients on tamoxifen had been reported, little evidence exists on association between these polymorphisms and adverse effects to tamoxifen. This study explored the association between CYP2D6 polymorphisms and tamoxifen effects, hitherto not studied in Sri Lanka. Methods: A retrospective preliminary study was carried out on 24 breast cancer patients on tamoxifen for minimally 3 months attending National Cancer Institute, Maharagama, Sri Lanka. They were not on CYP2D6-inhibiting drugs, chemotherapy or other endocrine therapy, and had no conditions that could occur as adverse effects to tamoxifen before starting the therapy. Their blood samples were collected, DNA was extracted and genotyped using SNaPshot Multiplex sequencing based single-nucleotide polymorphism (SNP assay. Results: SNP/allele frequencies detected: 1846G>A (confirmatory of *4 null allele=8.3%; 2549delA (confirmatory of *3 null allele=50%; 100C>T (suggestive of *10 reduced functional allele, in addition to other alleles=0%; combination of 2988G>A, -1584C and 2850C>T (strongly suggestive of *41 or other reduced functional allele=4.8%. Occurrence of heterozygous 2988G>A SNP with

Postoperative radiation therapy for adenoid cystic carcinoma

International Nuclear Information System (INIS)

Oguchi, Masahiko; Shikama, Naoto; Gomi, Koutarou; Shinoda, Atsunori; Nishikawa, Atsushi; Arakawa, Kazukiyo; Sasaki, Shigeru; Takei, Kazuyoshi; Sone, Syusuke

2000-01-01

The authors retrospectively assessed the usefulness of postoperative radiation therapy after local resection of adenoid cystic carcinoma, with emphasis on organ-conserving treatment and the cosmetic results. Between 1985 and 1995, 32 patients underwent local resection followed by postoperative radiation therapy with curative and organ-conserving intent. None of patients received any form of chemotherapy as part of their initial treatment. Radiation therapy was carried out by techniques that were appropriate for the site and extension of each tumor. The 5-year local control, disease-free, and overall survival rates of all patients were 76%, 68%, and 86%, respectively. The 5-year local control rate and disease-free survival rate of patients with microscopically positive margins were 89% and 75%, respectively, and higher than in patients with macroscopically residual disease, but no significant difference in 5-year overall survival rate was observed. The postoperative cosmetic results in 29 patients with head and neck lesions were evaluated. No difference was documented between the cosmetic results postoperatively setting and after postoperative radiotherapy, and no significant differences in cosmetic results were observed according to radiation dose. The combination of local resection with organ-conserving intent and postoperative radiation therapy provided good cosmetic results in patients with T1 or T2 lesions. Postoperative radiation therapy with smaller fractions is useful, because good local control can be achieved in patients with adenoid cystic carcinoma having microscopically positive margins without inducing any late adverse reactions. However, the number of patients was too small and the follow-up period was too short to draw any definite conclusion in regard to fraction size. A much longer follow-up study with a larger number patients will be required to accurately determine the optimal treatment intensity and duration of treatment. (K.H.)

Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer

NARCIS (Netherlands)

Meijer, Danielle; Sieuwerts, Anieta M.; Look, Maxime P.; van Agthoven, Ton; Foekens, John A.; Dorssers, Lambert C. J.

2008-01-01

Tamoxifen treatment of estrogen-dependent breast cancer ultimately loses its effectiveness due to the development of resistance. From a functional screen for identifying genes responsible for tamoxifen resistance in human ZR-75-1 breast cancer cells, fibroblast growth factor (FGF) 17 was recovered.

Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints - a prospective observational study.

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Rostock, Matthias; Fischer, Julia; Mumm, Andreas; Stammwitz, Ute; Saller, Reinhard; Bartsch, Hans Helge

2011-10-01

The antihormonal therapy of breast cancer patients with the antiestrogen tamoxifen often induces or aggravates menopausal complaints. As estrogen substitution is contraindicated, herbal alternatives, e.g. extracts of black cohosh are often used. A prospective observational study was carried out in 50 breast cancer patients with tamoxifen treatment. All patients had had surgery, most of them had undergone radiation therapy (87%) and approximately 50% had received chemotherapy. Every patient was treated with an isopropanolic extract of black cohosh (1-4 tablets, 2.5 mg) for 6 months. Patients recorded their complaints before therapy and after 1, 3, and 6 months of therapy using the menopause rating scale (MRS II). The reduction of the total MRS II score under black cohosh treatment from 17.6 to 13.6 was statistically significant. Hot flashes, sweating, sleep problems, and anxiety improved, whereas urogenital and musculoskeletal complaints did not change. In all, 22 patients reported adverse events, none of which were linked with the study medication; 90% reported the tolerability of the black cohosh extract as very good or good. Black cohosh extract seems to be a reasonable treatment approach in tamoxifen treated breast cancer patients with predominantly psychovegetative symptoms.

Study of Sperm Parameters and Sperm Fertility in Mice were Exposed to Tamoxifen during Embryonic Development

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J Soleimanirad

2017-05-01

Full Text Available Introduction: Tamoxifen is steroidal drug, which mainly treats breast cancer and also used to stimulate ovulation. The purpose of the present study was the evaluation of sperm parameters and fertility of mice whose mothers had received tamoxifen during pregnancy. Methods: In this study, 30 female and 15 male mice of NMRI were selected for mating. After mating female mice were randomly divided into two groups, the first group (control and second group (experimental. All of which contained 15 mice. From the day 13th day of pregnancy, experimental group has received tamoxifen with the dosage of 5 mg/kg for 7 days. After childbirth of the mated mice, male infants were selected. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation. After take sperm, sperm parameters (count, normality and motility, and sperm fertility was performed. In this study SPSS software and statistical t-test was used (p <0.001. Results: Studies showed that sperm parameters and sperm fertilization were significantly different. The number of sperm in the control group was 83.50±28.20 million, and in the experimental group was 60±14.14 million. There was a decrease in average sperm count in the experimental group compared with the control group (p <0.001. Our findings from in vitro fertilization culture media showed that embryos formation and oocyte disruption between control and experimental groups significantly different (p <0.001. Conclusion: The results showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility.

Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

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Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

2014-03-01

Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

Dried blood spots voor het bepalen van de serumconcentratie van tamoxifen en zijn actieve metaboliet endoxifen

NARCIS (Netherlands)

Jager, Nynke G L; Rosing, Hilde; Schellens, Jan H M; Beijnen, Jos H.; Linn, Sabine C.

2016-01-01

OBJECTIVE To establish the relationship between dried blood spot (DBS) and serum concentrations of tamoxifen and endoxifen in order to allow the use of DBS sampling, a simple and patient-friendly alternative to venous sampling, in clinical practice. The antiestrogenic effect of tamoxifen is

Evaluation of Nutritional Status Post Laparoscopic Sleeve Gastrectomy-5-Year Outcomes.

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Al-Mutawa, Aliaa; Al-Sabah, Salman; Anderson, Alfred Kojo; Al-Mutawa, Mohammad

2017-12-01

Obesity is considered a public health problem and has led to advancements in bariatric surgery. Laparoscopic sleeve gastrectomy (LSG) had become the most performed procedure worldwide; however, its consequences on nutritional status in the short and long term are of concern. A retrospective analysis of medical records and bariatric database of patients who underwent LSG from October 2008-September 2015 at Al-Amiri Hospital, Kuwait, was performed. Data regarding nutritional status along with demographic data were collected over a 5-year follow-up period. One thousand seven hundred ninety-three patients comprising of 74% females and 26% males were included. The greatest % total body weight loss (%TBWL) was at 18 months post-LSG (33%), corresponding to a % excess weight loss (%EWL) of 73.8%. With regard to nutritional status, vitamin B1 showed a significant drop at 3-5 years post-op in comparison to pre-op value, but stayed within the normal range throughout the study. Red blood cells count, hemoglobin, and hematocrit also showed a significant drop starting from 6 months post-op until the fifth year of follow-up. On the other hand, vitamins B6 and B12 showed a significant increase at 6 months post-op and decreased afterwards, but did not reach pre-op values. Vitamin D also showed a significant increase throughout the study period from deficient value at the pre-op time, but remained insufficient. Albumin, transferrin, folate, ferritin, iron, and vitamin B2 showed no significant changes at 5 years post-LSG compared to pre-op values. Little is known about the nutritional status and optimal nutritional care plan post-LSG, especially in the longer term. Nutritional deficiencies were prevalent prior and post-LSG. Some of the nutritional parameters improved and even reached the abnormal high level post-LSG. These observations highlight the importance of pre- and post-operative nutritional assessment and tailored supplementation to ensure optimal nutritional status.

Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the treatment and prevention of estrogen receptor-positive breast cancer.

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Kim, Chungyeul; Tang, Gong; Pogue-Geile, Katherine L; Costantino, Joseph P; Baehner, Frederick L; Baker, Joffre; Cronin, Maureen T; Watson, Drew; Shak, Steven; Bohn, Olga L; Fumagalli, Debora; Taniyama, Yusuke; Lee, Ahwon; Reilly, Megan L; Vogel, Victor G; McCaskill-Stevens, Worta; Ford, Leslie G; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman; Paik, Soonmyung

2011-11-01

Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) -positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors.

Transgenic mice for a tamoxifen-induced, conditional expression of the Cre recombinase in osteoclasts.

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Maria Arantzazu Sanchez-Fernandez

Full Text Available BACKGROUND: Studies on osteoclasts, the bone resorbing cells, have remained limited due to the lack of transgenic mice allowing the conditional knockout of genes in osteoclasts at any time during development or adulthood. METHODOLOGY/PRINCIPAL FINDING: We report here on the generation of transgenic mice which specifically express a tamoxifen-inducible Cre recombinase in osteoclasts. These mice, generated on C57BL/6 and FVB background, express a fusion Cre recombinase-ERT2 protein whose expression is driven by the promoter of cathepsin K (CtsK, a gene highly expressed in osteoclasts. We tested the cellular specificity of Cre activity in CtsKCreERT2 strains by breeding with Rosa26LacZ reporter mice. PCR and histological analyses of the CtsKCreERT2LacZ positive adult mice and E17.5 embryos show that Cre activity is restricted largely to bone tissue. In vitro, primary osteoclasts derived from the bone marrow of CtsKCreERT2+/-LacZ+/- adult mice show a Cre-dependent β-galactosidase activity after tamoxifen stimulation. CONCLUSIONS/SIGNIFICANCE: We have generated transgenic lines that enable the tamoxifen-induced, conditional deletion of loxP-flanked genes in osteoclasts, thus circumventing embryonic and postnatal gene lethality and avoiding gene deletion in other cell types. Such CtsKCreERT2 mice provide a convenient tool to study in vivo the different facets of osteoclast function in bone physiology during different developmental stages and adulthood of mice.

Prescribing tamoxifen in primary care for the prevention of breast cancer: a national online survey of GPs' attitudes.

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Smith, Samuel G; Foy, Robbie; McGowan, Jennifer A; Kobayashi, Lindsay C; DeCensi, Andrea; Brown, Karen; Side, Lucy; Cuzick, Jack

2017-06-01

The cancer strategy for England (2015-2020) recommends GPs prescribe tamoxifen for breast cancer primary prevention among women at increased risk. To investigate GPs' attitudes towards prescribing tamoxifen. In an online survey, GPs in England, Northern Ireland, and Wales ( n = 928) were randomised using a 2 × 2 between-subjects design to read one of four vignettes describing a healthy patient seeking a tamoxifen prescription. In the vignette, the hypothetical patient's breast cancer risk (moderate versus high) and the clinician initiating the prescription (GP prescriber versus secondary care clinician [SCC] prescriber) were manipulated in a 1:1:1:1 ratio. Outcomes were willingness to prescribe, comfort discussing harms and benefits, comfort managing the patient, factors affecting the prescribing decision, and awareness of tamoxifen and the National Institute for Health and Care Excellence (NICE) guideline CG164. Half (51.7%) of the GPs knew tamoxifen can reduce breast cancer risk, and one-quarter (24.1%) were aware of NICE guideline CG164. Responders asked to initiate prescribing (GP prescriber) were less willing to prescribe tamoxifen than those continuing a prescription initiated in secondary care (SCC prescriber) (68.9% versus 84.6%, P preventive therapy in secondary care before asking GPs to continue the patient's care may overcome some prescribing barriers. © British Journal of General Practice 2017.

Construction of a Nanodiamond–Tamoxifen Complex as a Breast Cancer Drug Delivery Vehicle

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Linda-Lucila Landeros-Martínez

2016-01-01

Full Text Available According to the World Health Organization, breast cancer represents 16% of all cancer cases in women and is the second most common cancer. In the past decades, the mortality among patients with metastasis breast cancer has been reduced significantly via drug delivery by means of nanodiamond therapies, which are both biocompatible and scalable. In this study, we determined a theoretical pathway for the construction of a nanodiamond–tamoxifen complex that will act as a drug delivery vehicle for targeting tumor tissues of breast cancer. The tamoxifen pharmacophore was defined and the binding zone was identified for the electrostatic interaction between tamoxifen and a functionalized site of a nanodiamond particle allowing for attachment of the payload (this drug to the surface of the nanodiamond particle. In addition, an analysis of the intermolecular interaction between the nanodiamond and tamoxifen was conducted, showing three hydrogen bonds complying fully with Lipinski’s rule of five, which states that a compound should have five or fewer hydrogen bonds to be permeating and easily absorbed by the body (qualitative prediction. All calculations were performed using the conceptual Density Functional Theory with the M06 functional and the basis set 6-31G(d. The solvent effect has been taken into account by an implicit model, the conductor like polarizable continuum model.

Estrogen Receptor (ESR1) mRNA Expression and Benefit From Tamoxifen in the Treatment and Prevention of Estrogen Receptor–Positive Breast Cancer

Science.gov (United States)

Kim, Chungyeul; Tang, Gong; Pogue-Geile, Katherine L.; Costantino, Joseph P.; Baehner, Frederick L.; Baker, Joffre; Cronin, Maureen T.; Watson, Drew; Shak, Steven; Bohn, Olga L.; Fumagalli, Debora; Taniyama, Yusuke; Lee, Ahwon; Reilly, Megan L.; Vogel, Victor G.; McCaskill-Stevens, Worta; Ford, Leslie G.; Geyer, Charles E.; Wickerham, D. Lawrence; Wolmark, Norman; Paik, Soonmyung

2011-01-01

Purpose Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) –positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. Patients and Methods We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. Results In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. Conclusion These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors. PMID:21947828

131I labeling of tamoxifen and biodistribution studies in rats

International Nuclear Information System (INIS)

Biber Muftuler, F.Z.; Unak, P.; Teksoz, S.; Acar, C.; Yolcular, S.; Yuerekli, Y.

2008-01-01

Tamoxifen [TAM ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine)] has been used as an antiestrogen drug for treatment and prevention of human breast cancer. Tamoxifen was labeled with 131 I using iodogen as an oxidizing agent. Mass spectroscopy of the cold standard showed that the labeling occurs in ortho position to the phenyl ether position of TAM as expected. Quality control, radiochemical yield and stability were established using the radioelectrophoresis method. The radiolabeled compound maintained its stability throughout working period of 24 h. Scintigraphic imaging was performed and tissue distribution was determined in Albino Wistar rats. According to biodistribution and imaging experiments the radiolabeled compound presented estrogen receptor (ER) specificity and it was uptaken by endometrium as well as breast tissue

Long-term bresults of radiotherapy combined with nedaplatin and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer: update on a phase II study

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Jingu Keiichi

2012-11-01

Full Text Available Abstract Background In 2006, we reported the effectiveness of chemoradiotherapy for postoperative recurrent esophageal cancer with a median observation period of 18 months. The purpose of the present study was to update the results of radiotherapy combined with nedaplatin and 5-fluorouracil (5-FU for postoperative loco-regional recurrent esophageal cancer. Methods Between 2000 and 2004, we performed a phase II study on treatment of postoperative loco-regional recurrent esophageal cancer with radiotherapy (60 Gy/30 fractions/6 weeks combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h and 5-FU (500 mg/m2/24 h for 5 days. The primary endpoint was overall survival rate, and the secondary endpoints were progression-free survival rate, irradiated-field control rate and chronic toxicity. Results A total of 30 patients were enrolled in this study. The regimen was completed in 76.7% of the patients. The median observation period for survivors was 72.0 months. The 5-year overall survival rate was 27.0% with a median survival period of 21.0 months. The 5-year progression-free survival rate and irradiated-field control rate were 25.1% and 71.5%, respectively. Grade 3 or higher late toxicity was observed in only one patient. Two long-term survivors had gastric tube cancer more than 5 years after chemoradiotherapy. Pretreatment performance status, pattern of recurrence (worse for patients with anastomotic recurrence and number of recurrent lesions (worse for patients with multiple recurrent lesions were statistically significant prognostic factors for overall survival. Conclusions Radiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. However, the prognosis of patients with multiple regional recurrence or anastomotic recurrence is very poor.

Effect of tamoxifen pre-treatment on the retention of tritiated oestradiol and 5. cap alpha. -dihydrotestosterone and on glucose metabolism in human breast carcinomas

Energy Technology Data Exchange (ETDEWEB)

Deshpande, N; Mitchell, I [Imperial Cancer Research Fund, London (UK). Labs.; Hughes, D

1978-05-01

The effect of pre-treatment with tamoxifen on glucose metabolism and retention of injected oestradiol-17B and 5..cap alpha..-dihydrotestosterone by human breast carcinomas were studied in patients undergoing mastectomy. The following effects were observed: the pretreatment reduced retention of oestradiol-17B whereas a small but statistically significant rise in 5..cap alpha..-dihydrotestosterone accumulation was observed. There was an increase in both phosphofructokinase (PFK) and glucose-6-phosphate dehydrogenase (G6PDH) activities in tumours from treated patients whereas ..cap alpha..-glycerolphosphate dehydrogenase (..cap alpha..-GPDH) activity was significantly reduced in the same tumours. The significance of these findings is discussed and it is argued that these changes in carbohydrate metabolism may not be due to the blocking of hormone receptors.

Postoperative radiotherapy for intracranial meningioma

International Nuclear Information System (INIS)

Chun, Ha Chung; Lee, Myung Za

2001-01-01

To evaluate the effectiveness and tolerance of postoperative external radiotherapy for patients with intracranial meningiomas. The records of thirty three patients with intracranial meningiomas who were treated with postoperative external irradiation at our institution between Feb, 1988 and Nov, 1999 were retrospectively analyzed. Median age of patients at diagnosis was 53 years with range of 17 to 68 years. Sites of involvement were parasagital, cerebral convexity, sphenoid ridge, parasellar and tentorium cerebella. Of 33 evaluated patients, 15 transitional, 10 meningotheliomatous, 4 hemangiopericytic, 3 atypical and 1 malignant meningioma were identified. Four patients underwent biopsy alone and remaining 29 patients underwent total tumor resection. A dose of 50 to 60 Gy was delivered in 28-35 daily fractions over a period of 5 to 7 weeks. Follow-up period ranged from 12 months to 8 years. The actuarial survival rates at 5 and 7 years for entire group of patients were 78% and 67%, respectively. The corresponding disease free survival rates were 73% and 61 %, respectively. The overall local control rate at 5 years was 83%. One out of 25 patients in benign group developed local failure, while 4 out of 8 patients in malignant group did local failure (p <0.05), Of 4 patients who underwent biopsy alone, 2 developed local failure. There was no significant difference in 5 year actuarial survival between patients who underwent total tumor resection and those who did biopsy alone. Patients whose age is under 60 showed slightly better survival than those whose age is 60 or older, although this was not statistically significant. There was no documented late complications in any patients. Based on our study, we might conclude that postoperative external beam radiotherapy tends to improve survival of patients with intracranial meningiomas comparing with surgery alone

Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy

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Freiberg FJ

2013-06-01

Full Text Available Florentina Joyce Freiberg,1 Juliane Matlach,1 Franz Grehn,1 Sabine Karl,2 Thomas Klink1 1Department of Ophthalmology, Julius Maximilian University, Wuerzburg, Germany; 2Institute of Mathematics, University of Wuerzburg, Wuerzburg, Germany Purpose: Scarring after glaucoma filtering surgery remains the most frequent cause for bleb failure. The aim of this study was to assess if the postoperative injection of bevacizumab reduces the number of postoperative subconjunctival 5-fluorouracil (5-FU injections. Further, the effect of bevacizumab as an adjunct to 5-FU on the intraocular pressure (IOP outcome, bleb morphology, postoperative medications, and complications was evaluated. Methods: Glaucoma patients (N = 61 who underwent trabeculectomy with mitomycin C were analyzed retrospectively (follow-up period of 25 ± 19 months. Surgery was performed exclusively by one experienced glaucoma specialist using a standardized technique. Patients in group 1 received subconjunctival applications of 5-FU postoperatively. Patients in group 2 received 5-FU and subconjunctival injection of bevacizumab. Results: Group 1 had 6.4 ± 3.3 (0–15 (mean ± standard deviation and range, respectively 5-FU injections. Group 2 had 4.0 ± 2.8 (0–12 (mean ± standard deviation and range, respectively 5-FU injections. The added injection of bevacizumab significantly reduced the mean number of 5-FU injections by 2.4 ± 3.08 (P ≤ 0.005. There was no significantly lower IOP in group 2 when compared to group 1. A significant reduction in vascularization and in cork screw vessels could be found in both groups (P < 0.0001, 7 days to last 5-FU, yet there was no difference between the two groups at the last follow-up. Postoperative complications were significantly higher for both groups when more 5-FU injections were applied. (P = 0.008. No significant difference in best corrected visual acuity (P = 0.852 and visual field testing (P = 0.610 between preoperative to last follow

CB1 and CB2 Receptors are Novel Molecular Targets for Tamoxifen and 4OH-Tamoxifen

OpenAIRE

Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

2013-01-01

Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for t...

MCAM/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelial-mesenchymal transition, decreased ER alpha expression and AKT activation

NARCIS (Netherlands)

Liang, Yuan-Ke; Zeng, De; Xiao, Ying-Sheng; Wu, Yang; Ouyang, Yan-Xiu; Chen, Min; Li, Yao-Chen; Lin, Hao-Yu; Wei, Xiao-Long; Zhang, Yong-Qu; Kruyt, Frank A. E.; Zhang, Guo-Jun

2017-01-01

Tamoxifen resistance presents a prominent clinical challenge in endocrine therapy for hormone sensitive breast cancer. However, the underlying mechanisms that contribute to tamoxifen resistance are not fully understood. In this study, we established a tamoxifen resistant MCF-7 cell line

Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.

Science.gov (United States)

Brentnall, Adam R; Cuzick, Jack; Byers, Helen; Segal, Corrinne; Reuter, Caroline; Detre, Simone; Sestak, Ivana; Howell, Anthony; Powles, Trevor J; Newman, William G; Dowsett, Mitchell

2016-08-01

A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen.

Lumpectomy Plus Tamoxifen or Anastrozole With or Without Whole Breast Irradiation in Women With Favorable Early Breast Cancer

International Nuclear Information System (INIS)

Poetter, Richard; Gnant, Michael; Kwasny, Werner; Tausch, Christoph; Handl-Zeller, Leonore; Pakisch, Brigitte; Taucher, Susanne; Hammer, Josef; Luschin-Ebengreuth, Gero; Schmid, Marianne; Sedlmayer, Felix; Stierer, Michael; Reiner, Georg; Kapp, Karin; Hofbauer, Friedrich; Rottenfusser, Andrea; Poestlberger, Sabine; Haider, Karin; Draxler, Wolfgang; Jakesz, Raimund

2007-01-01

Purpose: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial. Methods and Material: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy ± boost (n 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months. Results: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival. Conclusion: Breast radiotherapy ± boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse

Reprogramming of the ERRα and ERα target gene landscape triggers tamoxifen resistance in breast cancer.

Science.gov (United States)

Thewes, Verena; Simon, Ronald; Schroeter, Petra; Schlotter, Magdalena; Anzeneder, Tobias; Büttner, Reinhard; Benes, Vladimir; Sauter, Guido; Burwinkel, Barbara; Nicholson, Robert I; Sinn, Hans-Peter; Schneeweiss, Andreas; Deuschle, Ulrich; Zapatka, Marc; Heck, Stefanie; Lichter, Peter

2015-02-15

Endocrine treatment regimens for breast cancer that target the estrogen receptor-α (ERα) are effective, but acquired resistance remains a limiting drawback. One mechanism of acquired resistance that has been hypothesized is functional substitution of the orphan receptor estrogen-related receptor-α (ERRα) for ERα. To examine this hypothesis, we analyzed ERRα and ERα in recurrent tamoxifen-resistant breast tumors and conducted a genome-wide target gene profiling analysis of MCF-7 breast cancer cell populations that were sensitive or resistant to tamoxifen treatment. This analysis uncovered a global redirection in the target genes controlled by ERα, ERRα, and their coactivator AIB1, defining a novel set of target genes in tamoxifen-resistant cells. Beyond differences in the ERα and ERRα target gene repertoires, both factors were engaged in similar pathobiologic processes relevant to acquired resistance. Functional analyses confirmed a requirement for ERRα in tamoxifen- and fulvestrant-resistant MCF-7 cells, with pharmacologic inhibition of ERRα sufficient to partly restore sensitivity to antiestrogens. In clinical specimens (n = 1041), increased expression of ERRα was associated with enhanced proliferation and aggressive disease parameters, including increased levels of p53 in ERα-positive cases. In addition, increased ERRα expression was linked to reduced overall survival in independent tamoxifen-treated patient cohorts. Taken together, our results suggest that ERα and ERRα cooperate to promote endocrine resistance, and they provide a rationale for the exploration of ERRα as a candidate drug target to treat endocrine-resistant breast cancer. ©2015 American Association for Cancer Research.

The Prescription Pattern of Chinese Herbal Products That Contain Dang-Qui and Risk of Endometrial Cancer among Tamoxifen-Treated Female Breast Cancer Survivors in Taiwan: A Population-Based Study

Science.gov (United States)

Wu, Chien-Tung; Lai, Jung-Nien; Tsai, Yueh-Ting

2014-01-01

Purpose The increased practice of traditional Chinese medicine worldwide has raised concerns regarding herb-drug interactions. We analyzed the usage of Chinese herbal products containing dang-qui and investigated whether dang-qui therapy increases endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. Methods All patients newly diagnosed with invasive breast cancer who received tamoxifen treatment from January 1, 1998, to December 31, 2008 were selected from the National Health Insurance Research Database. The usage, frequency of service and type of Chinese herbal products containing dang-qui prescribed across the 31,970 survivors were evaluated. Logistic regression method was employed to estimate the odds ratios for utilization of Chinese herbal products containing dang-qui. Cox proportional hazard regression was performed to calculate the hazard ratio of endometrial cancer associated with dang-qui use within the cohort. Results Almost one in two study subjects had used dang-qui. Among 31,938 tamoxifen-treated breast cancer survivors, 157 cases of subsequent endometrial cancer were identified. The hazard ratio for development of endometrial cancer among breast cancer survivors aged 20–79 years who had taken dang-qui after tamoxifen treatment was decreased compared to survivors who had never used dang-qui (HR: 0.61, 95%CI: 0.44–0.84). To minimise potential confounding factors, women with breast cancer in the reproductive age were excluded from further analysis, and the negative relationship between dang-qui consumption and subsequent endometrial cancer among breast cancer survivors aged 55–79 years was still observed, although not significantly (HR: 0.74, 95%CI: 0.46–1.17). Conclusions Dang-qui consumption is common among breast cancer survivors aged 20–79 years and seems decrease the risk of subsequent endometrial cancer after less than a cumulative dose of 7,500 mg of tamoxifen treatment. PMID:25485843

Optimized axolotl (Ambystoma mexicanum) husbandry, breeding, metamorphosis, transgenesis and tamoxifen-mediated recombination.

Science.gov (United States)

Khattak, Shahryar; Murawala, Prayag; Andreas, Heino; Kappert, Verena; Schuez, Maritta; Sandoval-Guzmán, Tatiana; Crawford, Karen; Tanaka, Elly M

2014-03-01

The axolotl (Mexican salamander, Ambystoma mexicanum) has become a very useful model organism for studying limb and spinal cord regeneration because of its high regenerative capacity. Here we present a protocol for successfully mating and breeding axolotls in the laboratory throughout the year, for metamorphosing axolotls by a single i.p. injection and for axolotl transgenesis using I-SceI meganuclease and the mini Tol2 transposon system. Tol2-mediated transgenesis provides different features and advantages compared with I-SceI-mediated transgenesis, and it can result in more than 30% of animals expressing the transgene throughout their bodies so that they can be directly used for experimentation. By using Tol2-mediated transgenesis, experiments can be performed within weeks (e.g., 5-6 weeks for obtaining 2-3-cm-long larvae) without the need to establish germline transgenic lines (which take 12-18 months). In addition, we describe here tamoxifen-induced Cre-mediated recombination in transgenic axolotls.

Tamoxifen therapy improves overall survival in luminal A subtype of ductal carcinoma in situ: a study based on nationwide Korean Breast Cancer Registry database.

Science.gov (United States)

Hwang, Ki-Tae; Kim, Eun-Kyu; Jung, Sung Hoo; Lee, Eun Sook; Kim, Seung Il; Lee, Seokwon; Park, Heung Kyu; Kim, Jongjin; Oh, Sohee; Kim, Young A

2018-06-01

To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan-Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. Luminal A subtype (ER/PR+, HER2-) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P < .001) survival than no-tamoxifen therapy group. It had survival benefit only for luminal A subtype (P = .001). Tamoxifen therapy resulted in higher survival rate in subgroups with positive ER (P = .006), positive PR (P = .009), and negative HER2 (P < .001). In luminal A subtype, tamoxifen therapy showed lower hazard ratio (HR) compared to no-tamoxifen therapy (HR, 0.420; 95% CI 0.250-0.705; P = .001). Tamoxifen therapy was a significant independent factor by multivariate analysis (HR, 0.538; 95% CI 0.306-0.946; P = .031) as well as univariate analysis. Tamoxifen therapy group showed superior prognosis than the no-tamoxifen therapy group. Its prognostic influence was only effective for luminal A subtype. Patients with luminal A subtype showed higher survival rate than those with TN subtype. Active tamoxifen therapy is recommended for DCIS patients with luminal A subtype, and routine tests for ER, PR, and HER2 should be considered for DCIS.

The Role of Postoperative Radiotherapy in the Management of Intracranial Meningiomas

International Nuclear Information System (INIS)

Chang, Sei Kyung; Suh, Chang Ok; Shin, Hyun Soo; Kim, Gwi Eon

1994-01-01

Purpose: To evaluate the role of postoperative radiotherapy in the management of primary or recurrent intracranial meningiomas. Methods and Materials: A retrospective review of 34 intracranial meningioma patients referred to the Yonsei Cancer Center for postoperative radiotherapy between 1981 and 1990 was undertaken. Of the 34 patients, 24 patients received elective postoperative radiotherapy after total or subtotal resection(Group 1), and 10 patients received postoperative radiotherapy as a salvage treatment for recurrent tumors(Group 2). Ten patients received postoperative radiotherapy after total resection, and twenty-four after subtotal resection. Ten patients who had total tumor resection were referred for radiotherapy either because of angioblastic or malignant histologic type (4 patients in Group 1) or because of recurrent disease after initial surgery(6 patients in Group 2). Radiation dose of 50-56Gy was delivered over a period of 5-5.5 weeks using 4MV LINAC or Co-60 teletherapy unit. Results: Overall actuarial progression free survival (PFS) at 5 years was 80%. Survival was most likely affected by histologic subtypes. Five year PFS rate was 52% for benign angioblastic histology, as compared with 100% for classic benign histology. For malignant meningiomas, 5 year PFS rate was 44%. The recurrence rates of classic, angioblastic, and malignant type were 5%(1/21), 80%(4/5), and 50%(4/8), respectively. The duration between salvage post-operative radiotherapy and recurrence was longer than the duration between initial surgery and recurrence in the patients of group 2 with angioblastic or malignant histology. Conclusion: Postoperative radiotherapy of primary or recurrent intracranial meningiomas appears to be effective modality, especially in the patients with classic meningiomas. In angioblastic or malignant histologies, a more effective approach seems to be needed for decreasing recurrence rate

Prediction of postoperative pain after percutaneous nephrolithotomy

DEFF Research Database (Denmark)

Pedersen, Katja Venborg; Olesen, Anne Estrup; Osther, Palle Jørn Sloth

2013-01-01

Postoperative pain remains a significant problem and the individual variance in postoperative pain is not fully understood. In recent years, there has been focus on identifying risk factors predicting patients with high postoperative pain intensity or consumption of analgesics, which may facilitate...... thresholds were measured using electrical (single and 5 repeated) and pressure pain stimulation over the flank bilaterally (stone-side = operation side and control-side = non-operation side). Postoperative pain scores were recorded on a numerical rating scale and analgesic consumption was registered....... The responses to repeated electrical stimuli (temporal summation) were preoperatively increased on the stone-side compared to the control-side (P = 0.016). Preoperative electrical pain thresholds from the control-side correlated inversely with postoperative opioid consumption (single stimuli: ρ = -0.43, P

Migration of the Duraloc cup after 5 years.

Science.gov (United States)

Stihsen, Christoph; Pabinger, Christof; Radl, Roman; Rehak, Peter; Windhager, Reinhard

2008-12-01

The Duraloc cup is a frequently used metal-backed, porous-coated, hemispherical, press-fit acetabular component. Published data on loosening rates are contradictory. In this study we investigated migration patterns with computer-assisted Einzel-Bild-Roentgen-Analyse (EBRA) of 67 Duraloc 100 cups. Cup migration and clinical scores were analysed over a 5-year follow-up period. Median total migration of the Duraloc 100 cup was 1.21 mm at 5 years. Seventy-five percent of implants were radiologically stable at 2 years and 90% at 4 years. One cup loosened aseptically at 60 months, requiring revision. Cup diameters > or = 54 mm migrated significantly more than cups < 54 mm in diameter (p = 0.029 at 4 years). There was a significant correlation between high polyethylene wear and further migrating cups within the first post-operative year (p = 0.035 at 12 months). Our analysis revealed significantly higher wear in males (p = 0.029 at 4 years). Radiological loosening at two years could be calculated using receiver-operating characteristic curve analysis, and 1.2 mm as an adequate threshold value (sensitivity = 100%, specificity = 89%).

Principles of management of recurrence of breast cancer after tamoxifen therapy (abstract)

International Nuclear Information System (INIS)

Rasool, I.

1999-01-01

The management of recurrence of breast cancer after Tamoxifen therapy needs special attention. The recurrence can be local or distant. The patient, should be thoroughly investigated to find out exact sites of recurrences. Local recurrence is managed by excision, skin grafting or various types of flaps. If extensive radiation is administrated or if not given previously. The distant recurrence in patients who have had adjuvant menopausal status, sites of recurrence while life threatening or not and previous response. The patients who are post menopausal have responded to previous Tamoxifen therapy, long DFI and soft tissues and bony metastasis are best managed by Aromatase inhibitors i.e. Letrozole. (author)

Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability.

Science.gov (United States)

Jacobsson, S O; Rongård, E; Stridh, M; Tiger, G; Fowler, C J

2000-12-15

In the present study, the effects of the combination of tamoxifen ((Z)-2[p-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylamine citrate) and three cannabinoids (Delta(9)-tetrahydrocannabinol [Delta(9)-THC], cannabidiol, and anandamide [AEA]) upon the viability of C6 rat glioma cells was assessed at different incubation times and using different culturing concentrations of foetal bovine serum (FBS). Consistent with previous data for human glioblastoma cells, the tamoxifen sensitivity of the cells was increased as the FBS content of the culture medium was reduced from 10 to 0.4 and 0%. The cells expressed protein kinase C alpha and calmodulin (the concentration of which did not change significantly as the FBS concentration was reduced), but did not express estrogen receptors. Delta(9)-THC and cannabidiol, but not AEA, produced a modest reduction in cell viability after 6 days of incubation in serum-free medium, whereas no effects were seen in 10% FBS-containing medium. There was no observed synergy between the effects of tamoxifen and the cannabinoids upon cell viability.

Steroid receptor coactivators, HER-2 and HER-3 expression is stimulated by tamoxifen treatment in DMBA-induced breast cancer

International Nuclear Information System (INIS)

Moi, Line L Haugan; Flågeng, Marianne Hauglid; Gjerde, Jennifer; Madsen, Andre; Røst, Therese Halvorsen; Gudbrandsen, Oddrun Anita; Lien, Ernst A; Mellgren, Gunnar

2012-01-01

Steroid receptor coactivators (SRCs) may modulate estrogen receptor (ER) activity and the response to endocrine treatment in breast cancer, in part through interaction with growth factor receptor signaling pathways. In the present study the effects of tamoxifen treatment on the expression of SRCs and human epidermal growth factor receptors (HERs) were examined in an animal model of ER positive breast cancer. Sprague-Dawley rats with DMBA-induced breast cancer were randomized to 14 days of oral tamoxifen 40 mg/kg bodyweight/day or vehicle only (controls). Tumors were measured throughout the study period. Blood samples and tumor tissue were collected at sacrifice and tamoxifen and its main metabolites were quantified using LC-MS/MS. The gene expression in tumor of SRC-1, SRC-2/transcription intermediary factor-2 (TIF-2), SRC-3/amplified in breast cancer 1 (AIB1), ER, HER-1, -2, -3 and HER-4, as well as the transcription factor Ets-2, was measured by real-time RT-PCR. Protein levels were further assessed by Western blotting. Tamoxifen and its main metabolites were detected at high concentrations in serum and accumulated in tumor tissue in up to tenfolds the concentration in serum. Mean tumor volume/rat decreased in the tamoxifen treated group, but continued to increase in controls. The mRNA expression levels of SRC-1 (P = 0.035), SRC-2/TIF-2 (P = 0.002), HER-2 (P = 0.035) and HER-3 (P = 0.006) were significantly higher in tamoxifen treated tumors compared to controls, and the results were confirmed at the protein level using Western blotting. SRC-3/AIB1 protein was also higher in tamoxifen treated tumors. SRC-1 and SRC-2/TIF-2 mRNA levels were positively correlated with each other and with HER-2 (P ≤ 0.001), and the HER-2 mRNA expression correlated with the levels of the other three HER family members (P < 0.05). Furthermore, SRC-3/AIB1 and HER-4 were positively correlated with each other and Ets-2 (P < 0.001). The expression of SRCs and HER-2 and -3 is stimulated

Immediate Postoperative Pain Scores Predict Neck Pain Profile up to 1 Year Following Anterior Cervical Discectomy and Fusion.

Science.gov (United States)

Adogwa, Owoicho; Elsamadicy, Aladine A; Vuong, Victoria D; Mehta, Ankit I; Vasquez, Raul A; Cheng, Joseph; Bagley, Carlos A; Karikari, Isaac O

2018-05-01

Retrospective cohort review. To assess whether immediate postoperative neck pain scores accurately predict 12-month visual analog scale-neck pain (VAS-NP) outcomes following Anterior Cervical Discectomy and Fusion surgery (ACDF). This was a retrospective study of 82 patients undergoing elective ACDF surgery at a major academic medical center. Patient reported outcomes measures VAS-NP scores were recorded on the first postoperative day, then at 6-weeks, 3, 6, and 12-months after surgery. Multivariate correlation and logistic regression methods were utilized to determine whether immediate postoperative VAS-NP score accurately predicted 1-year patient reported VAS-NP Scores. Overall, 46.3% male, 25.6% were smokers, and the mean age and body mass index (BMI) were 53.7 years and 28.28 kg/m 2 , respectively. There were significant correlations between immediate postoperative pain scores and neck pain scores at 6 weeks VAS-NP ( P = .0015), 6 months VAS-NP ( P = .0333), and 12 months VAS-NP ( P = .0247) after surgery. Furthermore, immediate postoperative pain score is an independent predictor of 6 weeks, 6 months, and 1 year VAS-NP scores. Our study suggests that immediate postoperative patient reported neck pain scores accurately predicts and correlates with 12-month VAS-NP scores after an ACDF procedure. Patients with high neck pain scores after surgery are more likely to report persistent neck pain 12 months after index surgery.

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

Science.gov (United States)

Paik, Soonmyung; Shak, Steven; Tang, Gong; Kim, Chungyeul; Baker, Joffre; Cronin, Maureen; Baehner, Frederick L; Walker, Michael G; Watson, Drew; Park, Taesung; Hiller, William; Fisher, Edwin R; Wickerham, D Lawrence; Bryant, John; Wolmark, Norman

2004-12-30

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer. Copyright 2004 Massachusetts Medical Society.

Clinical evidence on the magnitude of change in growth pathway activity in relation to Tamoxifen resistance is required.

Science.gov (United States)

Mansouri, Sepideh; Farahmand, Leila; Teymourzadeh, Azin; Majidzadeh-A, Keivan

2017-08-08

Despite prolonged disease-free survival and overall survival rates in estrogen receptor (ER)-positive patients undergoing adjuvant treatment, Tamoxifen therapy tends to fail due to eventual acquisition of resistance. Although numerous studies have emphasized the role of receptor tyrosine kinases (RTKs) in the development of Tamoxifen resistance, inadequate clinical evidence is available regarding the alteration of biomarker expression during acquired resistance, thus undermining the validity of the findings. Results of two meta-analyses investigating the effect of HER2 status on the prognosis of Tamoxifen-receiving patients have demonstrated that despite HER2-negative patients having longer disease-free survival; there is no difference in overhaul survival between the two groups. Furthermore, due to the intricate molecular interactions among estrogen receptors including ERα36, ERα66, and also RTKs, it is not surprising that RTK suppression does not restore Tamoxifen sensitivity. In considering such a complex network, we speculate that by the time HER2/EGFR is suppressed via targeted therapies, activation of ERα66 and ERα36 initiate molecular signaling pathways downstream of RTKs, thereby enhancing cell proliferation even in the presence of both Tamoxifen and RTK inhibitors. Although clinical findings regarding the molecular pathways downstream of RTKs have been thoroughly discussed in this review, further clinical studies are required in determining a consistency between preclinical and clinical findings. Discovering the best targets in preventing tumor progression requires thorough comprehension of estrogen-dependent and estrogen-independent pathways during Tamoxifen resistance development. Indeed, exploring additional clinically-proven targets would allow for better characterized treatments being available for breast cancer patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ten-year study of postoperative complications following dental extractions in patients with inherited bleeding disorders.

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Hsieh, J-T; Klein, K; Batstone, M

2017-09-01

Dental extractions challenge the body's haemostatic mechanism. Postoperative bleeding from dental extraction can be prolonged, or even life threatening in patients with inherited bleeding disorders. Pre- and postoperative clotting factor replacements or systemic desmopressin (ddAVP) have been advocated at our institution to prevent bleeding complications in these patients. This study aimed to assess the postoperative bleeding rate in patients with inherited bleeding disorders that underwent dental extractions at our institution between 2003 and 2012. Patients with inherited bleeding disorders such as haemophilia A, haemophilia B, and von Willebrand's disease were included. Retrospective chart review was conducted. The result showed 53 extraction events occurred in 45 patients over the 10-year period. Ten out of 53 extraction events (18.9%) had postoperative bleeding requiring further factor replacement or ddAVP. Postoperative bleeding in one patient with mild haemophilia A was complicated by the development of inhibitors. Type and severity of bleeding disorder, bone removal, and use of a local haemostatic agent did not have any significant effect on postoperative bleeding. Despite the use of perioperative factors and desmopressin, the postoperative bleeding rates remain high for patients with inherited bleeding disorders. More studies are required to assess the safety and effectiveness of using local haemostatic control to achieve haemostasis following extractions. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Association of CYP2D6 and CYP2C19 polymorphisms and disease-free survival of Thai post-menopausal breast cancer patients who received adjuvant tamoxifen

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Chamnanphon M

2013-05-01

Full Text Available Montri Chamnanphon,1 Khunthong Pechatanan,2 Ekapob Sirachainan,3 Narumol Trachu,4 Wasun Chantratita,5 Ekawat Pasomsub,5 Wilai Noonpakdee,6 Insee Sensorn,1,7 Chonlaphat Sukasem11Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 2Department of Medicine, Phramongkutklao College of Medicine, 3Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 4Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 5Division of Virology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 6Department of Biochemistry, Faculty of Science, Mahidol University, 7Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, ThailandPurpose: To investigate the impact of CYP2D6 and CYP2C19 polymorphisms in predicting tamoxifen efficacy and clinical outcomes in Thai breast cancer patients.Methods: Polymorphisms of CYP2D6 and CYP2C19 were genotyped by the AmpliChip™ CYP450 Test (Roche Molecular Diagnostics, Branchburg, NJ, USA for 57 patients, who were matched as recurrent versus nonrecurrent breast cancers (n = 33 versus n = 24, respectively, with a 5-year follow-up.Results: Based on the genotype data, five CYP2D6 predicted phenotype groups were identified in this study including homozygous extensive metabolizer (13 of 57, 22.80%, extensive/intermediate metabolizer (23 of 57, 40.40%, extensive/poor metabolizer (3 of 57, 5.30%, homozygous intermediate metabolizer (14 of 57, 24.50%, and intermediate/poor metabolizer (4 of 57, 7.00%, and three CYP2C19 genotype groups including homozygous extensive metabolizer (27 of 57, 47.40%, extensive/intermediate metabolizer (27 of 57, 47.40%, and homozygous poor metabolizer (3 of 57, 5.30%. The CYP2D6 variant alleles were *10 (52 of 114, 45.60%, *5 (5 of 114, 4.40%, *41 (2 of 114, 1.80%, *4 (1 of 114, 0

AUDIT-C Alcohol Screening Results and Postoperative Inpatient Health Care Use

DEFF Research Database (Denmark)

Rubinsky, Anna D; Sun, Haili; Blough, David K

2012-01-01

BACKGROUND: Alcohol screening scores ≥5 on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) up to a year before surgery have been associated with postoperative complications, but the association with postoperative health care use is unknown. This study evaluated whether AUDIT...... surgery, but not increased hospital readmission within 30 days postdischarge, relative to the low-risk group. CONCLUSIONS: AUDIT-C screening results could be used to identify patients at risk for increased postoperative health care use who might benefit from preoperative alcohol interventions....... September 2006) and were hospitalized for nonemergent noncardiac major operations in the following year. Postoperative health care use was evaluated across 4 AUDIT-C risk groups (scores 0, 1 to 4, 5 to 8, and 9 to 12) using linear or logistic regression models adjusted for sociodemographics, smoking status...

Outcomes of WHO Grade I Meningiomas Receiving Definitive or Postoperative Radiotherapy

International Nuclear Information System (INIS)

Tanzler, Emily; Morris, Christopher G.; Kirwan, Jessica M.; Amdur, Robert J.; Mendenhall, William M.

2011-01-01

Purpose: We analyzed long-term local control and complications in patients with either pathologically confirmed or clinical World Health Organization Grade I meningiomas treated with definitive or postoperative radiotherapy (RT) at the University of Florida. Methods: Between 1984 and 2006, 146 patients were treated with definitive (n = 88) or postoperative RT after subtotal resection (n = 57) or gross total resection (n = 1). Patients were treated with conventional (n = 41), stereotactic (n = 103), or intensity-modulated RT (n = 2) to a median dose of 52.7 Gy and followed for a median of 7.3 years (range, 0.6-22.0 years) Results: The local control rates at 5 and 10 years were as follows: definitive RT, 99% and 99%; postoperative RT, 96% and 93%; and overall, 97% and 96%, respectively. The 5- and 10-year cause-specific survival rates were as follows: definitive RT 94% and 94%, postoperative RT, 100% and 96%; and overall, 96% and 95%, respectively. The 5- and 10-year overall survival rates were as follows: definitive RT, 81% and 75%; postoperative RT, 96% and 85%; and overall, 87% and 79%, respectively. Severe RT complications occurred in 6.8% of patients; severe surgery-related complications occurred in 10 (17%) of 58 patients treated surgically. Conclusions: The likelihood of cure after definitive RT or following subtotal resection is excellent. However, a small population of patients experience severe complications, even at the moderate dose used for this disease.

Air Travel Safety in Postoperative Breast Cancer Patients: A Systematic Review.

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Co, Michael; Ng, Judy; Kwong, Ava

2018-05-17

Air travel has long been a dilemma in post-breast cancer surgery patients. Anecdotal reports have described adverse outcomes on surgical wound, implants, and lymphedema during air travel. This review aims to evaluate the best evidence from the literature concerning the air travel safety in breast cancer patients. A comprehensive review was performed of the Medline, Embase, CINAHL, and Cochrane databases using a predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by 2 researchers. We reviewed the best evidence on air travel safety in postoperative breast cancer patients. Evidence was limited in the current literature to suggest adverse effects on postoperative mastectomy wounds and drains by high-altitude travel. Similarly, adverse effects on breast implants were limited to case reports and ex vivo experiments. A systematic review of 12 studies concluded that air travel is not associated with upper limb lymphedema after breast cancer surgery. Deep-vein thrombosis (DVT) is a known complication after air travel; in addition, malignancy itself is a known risk factor for DVT. Evidence of safety to continue tamoxifen during the period of air travel is lacking in the literature. Evidence to support the use of systemic DVT prophylaxis in general postoperative breast cancer patients is also limited. Best evidence from a large retrospective study suggested that mechanical antiembolism devices and early mobilization are the only measures required. Air travel is generally safe in patients after breast cancer surgery. Copyright © 2018. Published by Elsevier Inc.

Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye.

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Boneva, S K; Groß, T R; Schlecht, A; Schmitt, S I; Sippl, C; Jägle, H; Volz, C; Neueder, A; Tamm, E R; Braunger, B M

2016-06-14

Mice with a constitutive or tamoxifen-induced Cre recombinase (Cre) expression are frequently used research tools to allow the conditional deletion of target genes via the Cre-loxP system. Here we analyzed for the first time in a comprehensive and comparative way, whether retinal Cre expression or topical tamoxifen treatment itself would cause structural or functional changes, including changes in the expression profiles of molecular markers, glial reactivity and photoreceptor vulnerability. To this end, we characterized the transgenic α-Cre, Lmop-Cre and the tamoxifen-inducible CAGG-CreER™ mouse lines, all having robust Cre expression in the neuronal retina. In addition, we characterized the effects of topical tamoxifen treatment itself in wildtype mice. We performed morphometric analyses, immunohistochemical staining, in vivo ERG and angiography analyses and realtime RT-PCR analyses. Furthermore, the influence of Cre recombinase or topical tamoxifen exposure on neuronal vulnerability was studied by using light damage as a model for photoreceptor degeneration. Taken together, neither the expression of Cre, nor topical tamoxifen treatment caused detectable changes in retinal structure and function, the expression profiles of investigated molecular markers, glial reactivity and photoreceptor vulnerability. We conclude that the Cre-loxP system and its induction through tamoxifen is a safe and reliable method to delete desired target genes in the neural retina. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Gene expression changes induced by estrogen and selective estrogen receptor modulators in primary-cultured human endometrial cells: signals that distinguish the human carcinogen tamoxifen

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Pole, Jessica C.M.; Gold, Leslie I.; Orton, Terry; Huby, Russell; Carmichael, Paul L.

2005-01-01

Tamoxifen has long been the endocrine treatment of choice for women with breast cancer and is now employed for prophylactic use in women at high risk from breast cancer. Other selective estrogen receptor modulators (SERMs), such as raloxifene, mimic some of tamoxifen's beneficial effects and, like tamoxifen, exhibit a complex mixture of organ-specific estrogen agonist and antagonistic properties. However, accompanying the positive effects of tamoxifen has been the emergence of evidence for an increased risk of endometrial cancer associated with its use. A more complete understanding of the mechanism(s) of SERM carcinogenicity and endometrial effects is therefore required. We have sought to compare and characterise the transcript profile of tamoxifen, raloxifene and the agonist estradiol in human endometrial cells. Using primary cultures of human endometria, to best emulate the in vivo responses in a manageable in vitro system, we have shown 230 significant changes in gene expression for epithelial cultures and 83 in stromal cultures, either specific to 17β-estradiol, tamoxifen or raloxifene, or changed across more than one of the treatments. Considering the transcriptome as a whole, the endometrial responses to raloxifene or tamoxifen were more similar than either drug was to 17β-estradiol. Treatment of endometrial cultures with tamoxifen resulted in the largest number of gene changes relative to control cultures and a high proportion of genes associated with regulation of gene transcription, cell-cycle control and signal transduction. Tamoxifen-specific changes that might point towards mechanisms for its proliferative response in the endometrium included changes in retinoblastoma and c-myc binding proteins, the APCL, dihydrofolate reductase (DHFR) and E2F1 genes and other transcription factors. Tamoxifen was also found to give rise to the highest number of gene expression changes common to those that characterise malignant endometria. It is anticipated that this

Motivators and barriers of tamoxifen use as risk-reducing medication amongst women at increased breast cancer risk: a systematic literature review.

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Meiser, B; Wong, W K T; Peate, M; Julian-Reynier, C; Kirk, J; Mitchell, G

2017-01-01

Selective estrogen receptor modulators, such as tamoxifen, reduce breast cancer risk by up to 50% in women at increased risk for breast cancer. Despite tamoxifen's well-established efficacy, many studies show that most women are not taking up tamoxifen. This systematic literature review aimed to identify the motivators and barriers to tamoxifen use 's amongst high-risk women. Using MEDLINE, PsycINFO, and Embase plus reviewing reference lists of relevant articles published between 1995 and 2016, 31 studies (published in 35 articles) were identified, which addressed high-risk women's decisions about risk-reducing medication to prevent breast cancer and were peer-reviewed primary clinical studies. A range of factors were identified as motivators of, and barriers to, tamoxifen uptake including: perceived risk, breast-cancer-related anxiety, health professional recommendation, perceived drug effectiveness, concerns about side-effects, knowledge and access to information about side-effects, beliefs about the role of risk-reducing medication, provision of a biomarker, preference for other forms of breast cancer risk reduction, previous treatment experience, concerns about randomization in clinical trial protocols and finally altruism. Results indicate that the decision for high-risk women regarding tamoxifen use or non-use as a risk-reducing medication is not straightforward. Support of women making this decision is essential and needs to encompass the full range of factors, both informational and psychological.

Quality of life in cancer survivors 5 years or more after total gastrectomy: a case-control study.

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Lee, Seung Soo; Chung, Ho Young; Kwon, Oh Kyoung; Yu, Wansik

2014-01-01

This study investigated how total gastrectomy (TG), along with memories of cancer, affect the subjective wellness of survivors long after surgery. Rational approaches for effectively improving the quality of life (QoL) of these survivors were suggested. Between 2008 and 2013, QoL data of gastric cancer patients who underwent a curative TG, were obtained at 5-year postoperative follow-up visits (5-year survivors) and at visits beyond 5 years (long-term survivors). The control groups for these survivor groups were constructed from volunteers who visited our health-examination center for annual medical checkups. The Korean versions of the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the gastric cancer specific module, the EORTC QLQ-STO22, were used to assess QoL. Five-year survivors showed worse QoL compared to the control group in role functioning, social functioning, nausea/vomiting, appetite loss, financial difficulties, reflux, eating restrictions, taste, and body image, and better QoL in the emotional and cognitive functioning scales. In long-term survivors, deterioration in QoL were still apparent in financial difficulties, reflux, and eating restrictions, while QoL differences in the remaining scales had diminished. Surviving 5 years after TG does not result in living in a carefree state in terms of QoL. After 5 postoperative years, survivors still need extended care for deteriorated QoL indicators due to symptomatic, behavioral, and financial consequences of surgery. While relevant clinical and institutional approaches are required for corresponding declines in QoL, such efforts must extend beyond 5 postoperative years. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Implication of protein tyrosine phosphatase 1B in MCF-7 cell proliferation and resistance to 4-OH tamoxifen

International Nuclear Information System (INIS)

Blanquart, Christophe; Karouri, Salah-Eddine; Issad, Tarik

2009-01-01

The protein tyrosine phosphatase 1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) were initially thought to be mainly anti-oncogenic. However, overexpression of PTP1B and TC-PTP has been observed in human tumors, and recent studies have demonstrated that PTP1B contributes to the appearance of breast tumors by modulating ERK pathway. In the present work, we observed that decreasing the expression of TC-PTP or PTP1B in MCF-7 cells using siRNA reduced cell proliferation without affecting cell death. This reduction in proliferation was associated with decreased ERK phosphorylation. Moreover, selection of tamoxifen-resistant MCF-7 cells, by long-term culture in presence of 4-OH tamoxifen, resulted in cells that display overexpression of PTP1B and TC-PTP, and concomitant increase in ERK and STAT3 phosphorylation. siRNA experiments showed that PTP1B, but not TC-PTP, is necessary for resistance to 4-OH tamoxifen. Therefore, our work indicates that PTP1B could be a relevant therapeutic target for treatment of tamoxifen-resistant breast cancers.

Long-term outcomes following laparoscopic adjustable gastric banding: postoperative psychological sequelae predict outcome at 5-year follow-up.

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Scholtz, Samantha; Bidlake, Louise; Morgan, John; Fiennes, Alberic; El-Etar, Ashraf; Lacey, John Hubert; McCluskey, Sara

2007-09-01

NICE guidelines state that patients with psychological contra-indications should not be considered for bariatric surgery, including Laparoscopic Adjustable Gastric Banding (LAGB) surgery as treatment of morbid obesity, although no consistent correlation between psychiatric illness and long-term outcome in LAGB has been established. This is to our knowledge the first study to evaluate long-term outcomes in LAGB for a full range of DSM-IV defined psychiatric and eating disorders, and forms part of a research portfolio developed by the authors aimed at defining psychological predictors of bariatric surgery in the short-, medium- and long-term. Case notes of 37 subjects operated on between April 1997 and June 2000, who had undergone structured clinical interview during pre-surgical assessment to yield diagnoses of mental and eating disorders according to DSM-IV criteria were analyzed according to a set of operationally defined criteria. Statistical analysis was carried out to compare those with a poor outcome and those considered to have a good outcome in terms of psychiatric profile. In this group of mainly female, Caucasian subjects, ranging in age from 27 to 60 years, one-third were diagnosed with a mental disorder according to DSM-IV criteria. The development of postoperative DSM-IV defined binge eating disorder (BED) or depression strongly predicted poor surgical outcome, but pre-surgical psychiatric factors alone did not. Although pre-surgical psychiatric assessment alone cannot predict outcome, an absence of preoperative psychiatric illness should not reassure surgeons who should be mindful of postoperative psychiatric sequelae, particularly BED. The importance of providing an integrated biopsychosocial model of care in bariatric teams is highlighted.

ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen

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Sensorn I

2016-04-01

Full Text Available Insee Sensorn,1,* Chonlaphat Sukasem,2,* Ekaphop Sirachainan,3 Montri Chamnanphon,2 Ekawat Pasomsub,4 Narumol Trachu,5 Porntip Supavilai,1 Darawan Pinthong,1 Sansanee Wongwaisayawan6 1Department of Pharmacology, Faculty of Science, Mahidol University, 2Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 3Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 4Division of Virology, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 5Research Center, Faculty of Medicine, Ramathibodi Hospital, 6Division of Anatomical Pathology, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand *These authors contributed equally to this work Background: Genetic polymorphisms of drug-metabolizing enzymes and transporters have been extensively studied with regard to tamoxifen treatment outcomes. However, the results are inconclusive. Analysis of organ-specific metastasis may reveal the association of these pharmacogenetic factors. The aim of this study is to investigate the impact of CYP3A5, CYP2D6, ABCB1, and ABCC2 polymorphisms on the risk of all distant and organ-specific metastases in Thai patients who received tamoxifen adjuvant therapy. Methods: Genomic DNA was extracted from blood samples of 73 patients with breast cancer who received tamoxifen adjuvant therapy. CYP3A5 (6986A>G, CYP2D6 (100C>T, ABCB1 (3435C>T, and ABCC2 (-24C>T were genotyped using allelic discrimination real-time polymerase chain reaction assays. The impacts of prognostic clinical factors and genetic variants on disease-free survival were analyzed using the Kaplan–Meier method and Cox regression analysis. Results: In the univariate analysis, primary tumor size >5 cm was significantly associated with increased risk of distant metastasis (P=0

Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

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Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

2018-03-01

Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological Evaluation

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Konstantinos M. Kasiotis

2017-09-01

Full Text Available Aim of this work was to provide tamoxifen analogs with enhanced estrogen receptor (ER binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known ER inhibitor ICI182,780. Theoretical calculations and molecular modeling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

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Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

2017-09-01

Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

Valor da ultra-sonografia na avaliação das alterações endometriais em pacientes tratadas com tamoxifeno Value of sonographic endometrial findings in patients under tamoxifen therapy

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Arildo Corrêa Teixeira

2007-12-01

with hysteroscopic and anatomopathological results. RESULTS: Twenty-five patients, mean age 62.6 years, were selected. The mean time elapsed from the diagnosis of cancer was 4.3 years, and use of tamoxifen, three years. Twenty patients (80% were asymptomatic, and five (20% presented with bleeding. Ultrasound showed that 16% of patients had endometrial thickening ranging between 5 mm and 8 mm, 40% between 9 mm and 15 mm, and 44% above 15 mm. Hysteroscopy showed 40% of patients with atrophy, 16% with cystic atrophy, 28% with polyps and 16% with hyperplastic lesion. Anatomopathological study showed 35.2% of patients with normal results, 5.8% with atrophy, 29.4% with polyps and 11.7% with hyperplasia. One case of adenocarcinoma (5.8% was observed. CONCLUSION: Combined ultrasound and hysteroscopy have proven to be important allies in the evaluation of patients under tamoxifen therapy. Ultrasonography presents low specificity for detecting endometrial thickening, while hysteroscopy is more accurate in the detection of polyps, hyperplasia and neoplastic alterations.

Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

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Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

2016-07-29

Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.

Tool Weighs Benefits, Risks of Raloxifene or Tamoxifen to Prevent Breast Cancer

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Researchers have developed a benefit-risk index to help guide decisions on whether postmenopausal women at increased risk of developing breast cancer should take raloxifene or tamoxifen to reduce that risk.

An open, randomised, multicentre, phase 3 trial comparing the efficacy of two tamoxifen schedules in preventing gynaecomastia induced by bicalutamide monotherapy in prostate cancer patients.

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Bedognetti, Davide; Rubagotti, Alessandra; Conti, Giario; Francesca, Francesco; De Cobelli, Ottavio; Canclini, Luca; Gallucci, Michele; Aragona, Francesco; Di Tonno, Pasquale; Cortellini, Pietro; Martorana, Giuseppe; Lapini, Alberto; Boccardo, Francesco

2010-02-01

Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration. To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated. This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n=41) and weekly (n=39). Median follow-up was 24.2 mo. Daily bicalutamide (150 mg) plus daily tamoxifen 20mg continuously (daily group) or the same but with tamoxifen at 20mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in the weekly group and one in the daily group were discontinued for adverse events. For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires. Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p<0.0001), and it was more severe in patients who switched to weekly tamoxifen (p=0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively (p=0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far. This study demonstrated that

Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

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F.B. Silva

2015-02-01

Full Text Available The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF. Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23, a group that received chemotherapy + tamoxifen (n=21, and a group that received only tamoxifen (n=16. Plasma levels of NT-proBNP were assessed at 0 (T0, 6 (T6, and 12 (T12 months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

Chest wall stabilization and reconstruction: short and long-term results 5 years after the introduction of a new titanium plates system.

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De Palma, Angela; Sollitto, Francesco; Loizzi, Domenico; Di Gennaro, Francesco; Scarascia, Daniele; Carlucci, Annalisa; Giudice, Giuseppe; Armenio, Andrea; Ludovico, Rossana; Loizzi, Michele

2016-03-01

We report short and long-term results with the dedicated Synthes(®) titanium plates system, introduced 5 years ago, for chest wall stabilization and reconstruction. We retrospectively analyzed (January 2010 to December 2014) 27 consecutive patients (22 males, 5 females; range 16-83 years, median age 60 years), treated with this system: primary [3] and secondary [8] chest wall tumor; flail chest [5]; multiple ribs fractures [5]; sternal dehiscence-diastasis [3]; sternal fracture [1]; sternoclavicular joint dislocation [1]; Poland syndrome [1]. Short-term results were evaluated as: operating time, post-operative morbidity, mortality, hospital stay; long-term results as: survival, plates-related morbidity, spirometric values, chest pain [measured with Verbal Rating Scale (VRS) and SF12 standard V1 questionnaire]. Each patient received from 1 to 10 (median 2) titanium plates/splints; median operating time was 150 min (range: 115-430 min). Post-operative course: 15 patients (55.6%) uneventful, 10 (37%) minor complications, 2 (7.4%) major complications; no post-operative mortality. Median post-operative hospital stay was 13 days (range: 5-129 days). At a median follow-up of 20 months (range: 1-59 months), 21 patients (78%) were alive, 6 (22%) died. Three patients presented long-term plates-related morbidity: plates rupture [2], pin plate dislodgment [1]; two required a second surgical look. One-year from surgery median spirometric values were: FVC 3.31 L (90%), FEV1 2.46 L (78%), DLCO 20.9 mL/mmHg/min (76%). On 21 alive patients, 7 (33.3%) reported no pain (VRS score 0), 10 (47.6%) mild (score 2), 4 (19.1%) moderate (score 4), no-one severe (score >4); 15 (71.5%) reported none or mild, 6 (28.5%) moderate pain influencing quality of life. An optimal chest wall stabilization and reconstruction was achieved with the Synthes(®) titanium plates system, with minimal morbidity, no post-operative mortality, acceptable operating time and post-operative hospital stay. Long

Postoperative spine infections

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Paolo Domenico Parchi

2015-09-01

Full Text Available Postoperative spinal wound infection is a potentially devastating complication after operative spinal procedures. Despite the utilization of perioperative prophylactic antibiotics in recent years and improvements in surgical technique and postoperative care, wound infection continues to compromise patients’ outcome after spinal surgery. In the modern era of pending health care reform with increasing financial constraints, the financial burden of post-operative spinal infections also deserves consideration. The aim of our work is to give to the reader an updated review of the latest achievements in prevention, risk factors, diagnosis, microbiology and treatment of post-operative spinal wound infections. A review of the scientific literature was carried out using electronic medical databases Pubmed, Google Scholar, Web of Science and Scopus for the years 1973-2012 to obtain access to all publications involving the incidence, risk factors, prevention, diagnosis, treatment of postoperative spinal wound infections. We initially identified 119 studies; of these 60 were selected. Despite all the measures intended to reduce the incidence of surgical site infections in spine surgery, these remain a common and potentially dangerous complication.

Epidemiology of postoperative endophthalmitis in an Asian population: 11-year incidence and effect of intracameral antibiotic agents.

Science.gov (United States)

Tan, Colin S H; Wong, Hon Kiat; Yang, Francine P

2012-03-01

To describe the incidence of postoperative endophthalmitis after cataract surgery in a multiethnic Asian population over an 11-year period, compare the endophthalmitis rates before and after the use of intracameral antibiotic agents, and identify potential risk factors for endophthalmitis. Department of Ophthalmology, Tan Tock Seng Hospital, Singapore. Cohort study. The incidence and risk factors for postoperative endophthalmitis in patients who had cataract surgery over 11 years were reviewed. Subconjunctival antibiotic agents only were administered over 7 years; in the subsequent 4 years, intracameral cefazolin (1.0 mg/0.1 mL) was used. The overall incidence of postoperative endophthalmitis in 50,177 was 0.042%. Over the 7 years without intracameral antibiotics, the endophthalmitis rate was 0.064% (19/29,539). With the use of intracameral cefazolin, the incidence decreased to 0.01% (2/20,638) (multivariate odds ratio [OR], 13.6; 95% confidence interval [CI], 3.15-58.58; P<.001). The independent risk factors for endophthalmitis were age (OR, 1.05; 95% CI, 1.01-1.09; P=.025) and male sex (0.06% versus 0.02%; OR, 2.96; 95% CI; 1.15-7.65; P=.025). There was a significant reduction in the rate of postoperative endophthalmitis in a multiethnic Asian population with the use of intracameral cefazolin. Men and older patients were at a higher risk for endophthalmitis. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

The temporal outcomes of open versus arthroscopic knotted and knotless rotator cuff repair over 5 years

Science.gov (United States)

Lucena, Thomas R; Lam, Patrick H; Millar, Neal L

2015-01-01

Background The present study aimed to determine how repair technique influenced structural and clinical outcomes at 5 years post-surgery. Methods Three cohorts of patients had repair of a symptomatic rotator cuff tear using (i) an open double-row mattress repair technique (n = 25); (ii) arthroscopic single-row simple suture knotted technique (n = 25); or (iii) arthroscopic single-row inverted mattress knotless technique (n = 36) by one surgeon. Standardized patient- and examiner-determined outcomes were obtained pre-operatively and postoperatively with a validated protocol, ultrasound were also performed at the same time. Results Retear occurred more often after open repair (48%) at 5 years than after arthroscopic knotted (33%) and arthroscopic knotless (26%) repair. Retear was associated with increasing age, pre-operative tear size and weaker pre-operative and 5 years postoperative cuff strength. Between 2 years and 5 years, the open repair group experienced an increase in the frequency of pain during activity, as well as in the difficulty experienced and the severity of pain during overhead activities (p repair group. Conclusions At 5-year follow-up, arthroscopic rotator cuff repair techniques resulted in fewer retears and better outcomes compared to an open double-row technique. PMID:27582985

Outcome from 5-year live surgical demonstrations in urinary stone treatment: are outcomes compromised?

NARCIS (Netherlands)

Legemate, Jaap D.; Zanetti, Stefano P.; Baard, Joyce; Kamphuis, Guido M.; Montanari, Emanuele; Traxer, Olivier; de la Rosette, Jean Jmch

2017-01-01

To compare intra- and post-operative outcomes of endourological live surgical demonstrations (LSDs) and routine surgical practice (RSP) for urinary stones. Consecutive ureterorenoscopic (URS) and percutaneous (PNL) urinary stone procedures over a 5-year period were reviewed. Procedures were divided

Postoperative Complications in the Ahmed Baerveldt Comparison Study during Five Years of Follow-up

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Budenz, Donald L.; Feuer, William J.; Barton, Keith; Schiffman, Joyce; Costa, Vital P.; Godfrey, David G.; Buys, Yvonne M.

2016-01-01

PURPOSE To compare the late complications in the Ahmed Baerveldt Comparison Study during 5 years of follow-up. DESIGN Multicenter, prospective, randomized clinical trial. METHODS SETTINGS Sixteen international clinical centers. STUDY POPULATION Two hundred seventy six subjects aged 18 to 85 years with previous intraocular surgery or refractory glaucoma with intraocular pressure of > 18 mmHg. INTERVENTIONS Ahmed Glaucoma Valve FP7 or Baerveldt Glaucoma Implant BG 101-350. MAIN OUTCOME MEASURES Late postoperative complications (beyond 3 months), reoperations for complications, and decreased vision from complications. RESULTS Late complications developed in 56 subjects (46.8 ± 4.8 5 year cumulative % ± SE) in the Ahmed Glaucoma Valve group and 67 (56.3 ± 4.7 5 year cumulative % ± SE) in the Baerveldt Glaucoma Implant group (P = 0.082). The cumulative rates of serious complications were 15.9% and 24.7% in the Ahmed Glaucoma Valve and Baerveldt Glaucoma Implant groups respectively (P = 0.034) although this was largely driven by subjects who had tube occlusions in the two groups (0.8% in the Ahmed Glaucoma Valve group and 5.7% in the Baerveldt Glaucoma Implant group, P = 0.037). Both groups had a relatively high incidence of persistent diplopia (12%) and corneal edema (20%), although half of the corneal edema cases were likely due to pre-existing causes other than the aqueous shunt. The incidence of tube erosion was 1% and 3% in the Ahmed Glaucoma Valve and Baerveldt Glaucoma Implant groups, respectively (P = 0.04). CONCLUSIONS Long term rates of vision threatening complications and complications resulting in reoperation were higher in the Baerveldt Glaucoma Implant than the Ahmed Glaucoma Valve group over 5 years of follow-up. PMID:26596400

Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1.

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Zhu, Yinghua; Liu, Yujie; Zhang, Chao; Chu, Junjun; Wu, Yanqing; Li, Yudong; Liu, Jieqiong; Li, Qian; Li, Shunying; Shi, Qianfeng; Jin, Liang; Zhao, Jianli; Yin, Dong; Efroni, Sol; Su, Fengxi; Yao, Herui; Song, Erwei; Liu, Qiang

2018-04-23

Tamoxifen resistance is accountable for relapse in many ER-positive breast cancer patients. Most of these recurrent patients receive chemotherapy, but their chemosensitivity is unknown. Here, we report that tamoxifen-resistant breast cancer cells express significantly more BARD1 and BRCA1, leading to resistance to DNA-damaging chemotherapy including cisplatin and adriamycin, but not to paclitaxel. Silencing BARD1 or BRCA1 expression or inhibition of BRCA1 phosphorylation by Dinaciclib restores the sensitivity to cisplatin in tamoxifen-resistant cells. Furthermore, we show that activated PI3K/AKT pathway is responsible for the upregulation of BARD1 and BRCA1. PI3K inhibitors decrease the expression of BARD1 and BRCA1 in tamoxifen-resistant cells and re-sensitize them to cisplatin both in vitro and in vivo. Higher BARD1 and BRCA1 expression is associated with worse prognosis of early breast cancer patients, especially the ones that received radiotherapy, indicating the potential use of PI3K inhibitors to reverse chemoresistance and radioresistance in ER-positive breast cancer patients.

Polypoid endometriosis mimicking invasive cancer in an obese, postmenopausal tamoxifen user

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William T. Jaegle

2017-11-01

Précis: Endometriosis is a benign estrogen dependent condition rarely problematic in a postmenopausal patient. Tamoxifen use in the setting of an obese patient may contribute to a proliferation of pre-existing endometriosis which resembles an aggressive late-stage gynecological malignancy.

Development of biodegradable polymer based tamoxifen citrate loaded nanoparticles and effect of some manufacturing process parameters on them: a physicochemical and in-vitro evaluation

Directory of Open Access Journals (Sweden)

Basudev Sahana

2010-08-01

Full Text Available Basudev Sahana, Kousik Santra, Sumit Basu, Biswajit MukherjeeDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata, IndiaAbstract: The aim of the present study was to develop nanoparticles of tamoxifen citrate, a non-steroidal antiestrogenic drug used for the treatment of breast cancer. Biodegradable poly (D, L- lactide-co-glycolide-85:15 (PLGA was used to develop nanoparticles of tamoxifen citrate by multiple emulsification (w/o/w and solvent evaporation technique. Drug-polymer ratio, polyvinyl alcohol concentrations, and homogenizing speeds were varied at different stages of preparation to optimize the desired size and release profile of drug. The characterization of particle morphology and shape was performed by field emission scanning electron microscope (FE-SEM and particle size distribution patterns were studied by direct light scattering method using zeta sizer. In vitro drug release study showed that release profile of tamoxifen from biodegradable nanoparticles varied due to the change in speed of centrifugation for separation. Drug loading efficiency varied from 18.60% to 71.98%. The FE-SEM study showed that biodegradable nanoparticles were smooth and spherical in shape. The stability studies of tamoxifen citrate in the experimental nanoparticles showed the structural integrity of tamoxifen citrate in PLGA nanoparticles up to 60°C in the tested temperatures. Nanoparticles containing tamoxifen citrate could be useful for the controlled delivery of the drug for a prolonged period.Keywords: biodegradable, nanoparticles, PLGA, stability, tamoxifen citrate

Postoperative intraspinal subdural collections after pediatric posterior fossa tumor resection: incidence, imaging, and clinical features.

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Harreld, J H; Mohammed, N; Goldsberry, G; Li, X; Li, Y; Boop, F; Patay, Z

2015-05-01

Postoperative intraspinal subdural collections in children after posterior fossa tumor resection may temporarily hinder metastasis detection by MR imaging or CSF analysis, potentially impacting therapy. We investigated the incidence, imaging and clinical features, predisposing factors, and time course of these collections after posterior fossa tumor resection. Retrospective review of postoperative spine MRI in 243 children (5.5 ± 4.6 years of age) from our clinical data base postresection of posterior fossa tumors from October 1994 to August 2010 yielded 37 (6.0 ± 4.8 years of age) subjects positive for postoperative intraspinal subdural collections. Their extent and signal properties were recorded for postoperative (37/37), preoperative (15/37), and follow-up spine (35/37) MRI. Risk factors were compared with age-matched internal controls (n = 37, 5.9 ± 4.5 years of age). Associations of histology, hydrocephalus and cerebellar tonsillar herniation, and postoperative intracranial subdural collections with postoperative intraspinal subdural collections were assessed by the Fisher exact test or χ(2) test. The association between preoperative tumor volume and postoperative intraspinal subdural collections was assessed by the Wilcoxon rank sum test. The overall incidence of postoperative intraspinal subdural collections was 37/243 (15.2%), greatest ≤7 days postoperatively (36%); 97% were seen 0-41 days postoperatively (12.9 ± 11.0 days). They were T2 hyperintense and isointense to CSF on T1WI, homogeneously enhanced, and resolved on follow-up MR imaging (35/35). None were symptomatic. They were associated with intracranial subdural collections (P = .0011) and preoperative tonsillar herniation (P = .0228). Postoperative intraspinal subdural collections are infrequent and clinically silent, resolve spontaneously, and have a distinctive appearance. Preoperative tonsillar herniation appears to be a predisposing factor. In this series, repeat MR imaging by 4 weeks

Assessment of surgical treatment and postoperative nutrition in gastric cancer patients older than 80 years.

Science.gov (United States)

Nakanoko, Tomonori; Kakeji, Yoshihiro; Ando, Koji; Nakashima, Yuichiro; Ohgaki, Kippei; Kimura, Yasue; Saeki, Hiroshi; Oki, Eiji; Morita, Masaru; Maehara, Yoshihiko

2015-01-01

A gastrectomy for gastric cancer is sometimes required in patients older than 80 years due to the continuously increasing age of society. However, if a gastrectomy worsens the postoperative quality of life and daily activity in elderly patients because of poor nutrition, the procedure may not always be a useful treatment strategy. Clinicopathological data of patients with gastric cancer who underwent a gastrectomy at our Department between 1998 and 2008 (N=471) were collected and analyzed. The results of treatment for patients older than 80 years (N=41) were analyzed and compared against those of patients younger than 80 years (N=430). Patients older than 80 years had a higher frequency of preoperative co-morbidities than patients younger than 80 years. However, there was no statistical difference in postoperative complications regarding nutrition between the two groups. Older age is not a determinant of poor nutrition following gastrectomy. Gastrectomy for gastric cancer is, therefore, a useful treatment strategy, regardless of ageing. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1-98 trial

DEFF Research Database (Denmark)

Ewertz, Marianne; Gray, Kathryn P; Regan, Meredith M

2012-01-01

To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up....

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

Science.gov (United States)

Meybohm, Patrick; Kohlhaas, Madeline; Stoppe, Christian; Gruenewald, Matthias; Renner, Jochen; Bein, Berthold; Albrecht, Martin; Cremer, Jochen; Coburn, Mark; Schaelte, Gereon; Boening, Andreas; Niemann, Bernd; Sander, Michael; Roesner, Jan; Kletzin, Frank; Mutlak, Haitham; Westphal, Sabine; Laufenberg-Feldmann, Rita; Ferner, Marion; Brandes, Ivo F; Bauer, Martin; Stehr, Sebastian N; Kortgen, Andreas; Wittmann, Maria; Baumgarten, Georg; Meyer-Treschan, Tanja; Kienbaum, Peter; Heringlake, Matthias; Schoen, Julika; Treskatsch, Sascha; Smul, Thorsten; Wolwender, Ewa; Schilling, Thomas; Fuernau, Georg; Bogatsch, Holger; Brosteanu, Oana; Hasenclever, Dirk; Zacharowski, Kai

2018-03-26

Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Tamoxifen effects on subjective and psychosexual well-being, in a randomised breast cancer study comparing high-dose and standard-dose chemotherapy

NARCIS (Netherlands)

Mourits, MJ; Bockermann, [No Value; de Vries, EG; van der Zee, AG; ten Hoor, KA; van der Graaf, WT; Sluiter, WJ; Willemse, PH

2002-01-01

To evaluate the impact of tamoxifen on subjective and psychosexual well-being in breast cancer patients in relation to type of prior chemotherapy and menopausal status. Longitudinal interview study in breast cancer patients during and after adjuvant tamoxifen use. Menopausal status was defined by

Limited predictive value of achieving beneficial plasma (Z)-endoxifen threshold level by CYP2D6 genotyping in tamoxifen-treated Polish women with breast cancer

International Nuclear Information System (INIS)

Hennig, Ewa E.; Piatkowska, Magdalena; Karczmarski, Jakub; Goryca, Krzysztof; Brewczynska, Elzbieta; Jazwiec, Radoslaw; Kluska, Anna; Omiotek, Robert; Paziewska, Agnieszka; Dadlez, Michal; Ostrowski, Jerzy

2015-01-01

Tamoxifen, the most frequently used drug for treating estrogen receptor-positive breast cancer, must be converted into active metabolites to exert its therapeutic efficacy, mainly through CYP2D6 enzymes. The objective of this study was to investigate the impact of CYP2D6 polymorphisms on (Z)-endoxifen-directed tamoxifen metabolism and to assess the usefulness of CYP2D6 genotyping for identifying patients who are likely to have insufficient (Z)-endoxifen concentrations to benefit from standard therapy. Blood samples from 279 Polish women with breast cancer receiving tamoxifen 20 mg daily were analyzed for CYP2D6 genotype and drug metabolite concentration. Steady-state plasma levels of tamoxifen and its 14 metabolites were measured by using the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. In nearly 60 % of patients, including over 30 % of patients with fully functional CYP2D6, (Z)-endoxifen concentration was below the predefined threshold of therapeutic efficacy. The most frequently observed CYP2D6 genotype was EM/PM (34.8 %), among which 83.5 % of patients had a combination of wild-type and *4 alleles. Plasma concentration of five metabolites was significantly correlated with CYP2D6 genotype. For the first time, we identified an association between decreased (E/Z)-4-OH-N-desmethyl-tamoxifen-β-D-glucuronide levels (r 2 = 0.23; p < 10 −16 ) and increased CYP2D6 functional impairment. The strongest correlation was observed for (Z)-endoxifen, whose concentration was significantly lower in groups of patients carrying at least one CYP2D6 null allele, compared with EM/EM patients. The CYP2D6 genotype accounted for plasma level variability of (Z)-endoxifen by 27 % (p < 10 −16 ) and for the variability of metabolic ratio indicating (Z)-endoxifen-directed metabolism of tamoxifen by 51 % (p < 10 −43 ). The majority of breast cancer patients in Poland may not achieve a therapeutic level of (Z)-endoxifen upon receiving a standard

Postoperative radiotherapy for parotid gland malignancy

Energy Technology Data Exchange (ETDEWEB)

Eom, Keun Yong; Wu, Hong Gyun; Kim, Jae Sung; Park, Charn Il; Kim, Kwang Hyun; Lee, Chae Seo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, In Ah [Bundang Seoul National University Hospital, Seongnam (Korea, Republic of)

2005-09-15

The aim of this study was to evaluate the clinical results of postoperative radiotherapy for parotid gland malignancy, and determine prognostic factors for locoregional control and survival. Between 1980 and 2002, 130 patients with parotid malignancy were registered in the database of the Department of Radiation Oncology, Seoul National University Hospital. The subjects of this analysis were the 72 of these 130 patients who underwent postoperative irradiation. There were 42 males and 30 females, with a median age of 46.5 years. The most common histological type was a mucoepidermoid carcinoma. There were 6, 23, 23 and 20 patients in Stages I, II, III and IV, respectively. The median dose to the tumor bed was 60 Gy, with a median fraction size of 1.8 Gy. The overall 5 and 10 year survival rates were 85 and 76%, respectively. The five-year locoregional control rate was 85%, which reached a plateau phase after 6 years. Sex and histological type were found to be statistically significant for overall survival from a multivariate analysis. No other factors, including age, facial nerve palsy and stage, were related to overall survival. For locoregional control, nodal involvement and positive resection margin were associated with poor local control. Histological type, tumor size, perineural invasion and type of surgery were not significant for locoregional control. A high survival rate of parotid gland malignancies, with surgery and postoperative radiotherapy, was confirmed. Sex and histological type were significant prognostic factors for overall survival. Nodal involvement and a positive resection margin were associated with poor locoregional control.

Tamoxifen from Failed Contraceptive Pill to Best-Selling Breast Cancer Medicine: A Case-Study in Pharmaceutical Innovation

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Viviane M. Quirke

2017-09-01

Full Text Available Today, tamoxifen is one of the world's best-selling hormonal breast cancer drugs. However, it was not always so. Compound ICI 46,474 (as it was first known was synthesized in 1962 within a project to develop a contraceptive pill in the pharmaceutical laboratories of ICI (now part of AstraZeneca. Although designed to act as an anti-estrogen, the compound stimulated, rather than suppressed ovulation in women. This, and the fact that it could not be patented in the USA, its largest potential market, meant that ICI nearly stopped the project. It was saved partly because the team's leader, Arthur Walpole, threatened to resign, and pressed on with another project: to develop tamoxifen as a treatment for breast cancer. Even then, its market appeared small, because at first it was mainly used as a palliative treatment for advanced breast cancer. An important turning point in tamoxifen's journey from orphan drug to best-selling medicine occurred in the 1980s, when clinical trials showed that it was also useful as an adjuvant to surgery and chemotherapy in the early stages of the disease. Later, trials demonstrated that it could prevent its occurrence or re-occurrence in women at high risk of breast cancer. Thus, it became the first preventive for any cancer, helping to establish the broader principles of chemoprevention, and extending the market for tamoxifen and similar drugs further still. Using tamoxifen as a case study, this paper discusses the limits of the rational approach to drug design, the role of human actors, and the series of feedback loops between bench and bedside that underpins pharmaceutical innovation. The paper also highlights the complex evaluation and management of risk that are involved in all therapies, but more especially perhaps in life-threatening and emotion-laden diseases like cancer.

Postoperative Nomogram Predicting the 10-Year Probability of Prostate Cancer Recurrence After Radical Prostatectomy

Science.gov (United States)

Stephenson, Andrew J.; Scardino, Peter T.; Eastham, James A.; Bianco, Fernando J.; Dotan, Zohar A.; DiBlasio, Christopher J.; Reuther, Alwyn; Klein, Eric A.; Kattan, Michael W.

2007-01-01

Purpose A postoperative nomogram for prostate cancer recurrence after radical prostatectomy (RP) has been independently validated as accurate and discriminating. We have updated the nomogram by extending the predictions to 10 years after RP and have enabled the nomogram predictions to be adjusted for the disease-free interval that a patient has maintained after RP. Methods Cox regression analysis was used to model the clinical information for 1,881 patients who underwent RP for clinically-localized prostate cancer by two high-volume surgeons. The model was externally validated separately on two independent cohorts of 1,782 patients and 1,357 patients, respectively. Disease progression was defined as a rising prostate-specific antigen (PSA) level, clinical progression, radiotherapy more than 12 months postoperatively, or initiation of systemic therapy. Results The 10-year progression-free probability for the modeling set was 79% (95% CI, 75% to 82%). Significant variables in the multivariable model included PSA (P = .002), primary (P < .0001) and secondary Gleason grade (P = .0006), extracapsular extension (P < .0001), positive surgical margins (P = .028), seminal vesicle invasion (P < .0001), lymph node involvement (P = .030), treatment year (P = .008), and adjuvant radiotherapy (P = .046). The concordance index of the nomogram when applied to the independent validation sets was 0.81 and 0.79. Conclusion We have developed and validated as a robust predictive model an enhanced postoperative nomogram for prostate cancer recurrence after RP. Unique to predictive models, the nomogram predictions can be adjusted for the disease-free interval that a patient has achieved after RP. PMID:16192588

Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: A Dutch TEAM trial analysis

NARCIS (Netherlands)

J.G.H. van Nes; L.V. Beex (Louk); C.M. Seynaeve (Caroline); H. Putter (Hein); A. Sramek (Alexandr); S. Lardenoije (Susanne); M.D.-D.E. Carpentier (Marjolijn Duijm-D.E.); I. Van Rongen (Inge); J.W.R. Nortier (Johan W. R.); H.M. Zonderland (Harmine); C.J.H. van de Velde (Cornelis)

2015-01-01

textabstractBackground. Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane

Global characterization of signalling networks associated with tamoxifen resistance in breast cancer

DEFF Research Database (Denmark)

Browne, Brigid C.; Hochgräfe, Falko; Wu, Jianmin

2013-01-01

R cells. Phosphorylation of the tyrosine kinase Yes and expression of the actin‐binding protein myristoylated alanine‐rich C‐kinase substrate (MARCKS) were increased two‐ and eightfold in TamR cells respectively, and these proteins were selected for further analysis. Knockdown of either protein in Tam......Acquired resistance to the anti‐estrogen tamoxifen remains a significant challenge in breast cancer management. In this study, we used an integrative approach to characterize global protein expression and tyrosine phosphorylation events in tamoxifen‐resistant MCF7 breast cancer cells (Tam...... was perturbed in TamR cells, together with pathways enriched for proteins associated with growth factor, cell–cell and cell matrix‐initiated signalling. Consistent with known roles for Ras/MAPK and PI3‐kinase signalling in tamoxifen resistance, tyrosine‐phosphorylated MAPK1, SHC1 and PIK3R2 were elevated in Tam...

Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer.

Science.gov (United States)

Eggemann, Holm; Altmann, Udo; Costa, Serban-Dan; Ignatov, Atanas

2018-02-01

Our goal was to compare the survival advantage of tamoxifen (TAM) and aromatase inhibitor (AI) in female (FBC) and male breast cancer (MBC). We performed a retrospective study of 2785 FBC and 257 MBC patients treated with hormonal therapy. The median follow-up was 106 months (range 3-151 months) and 42 months (range 2-115 months) for FBC and MBC, respectively. The patients were divided into two groups according to the hormonal therapy used: TAM-treated and AI-treated. MBC was characterized by older age, advanced tumor stage, and higher rate of lymph node metastases, in comparison with FBC. Matching analysis was performed using six prognostic criteria: patient age, tumor stage, tumor grade, lymph node status, human epidermal growth factor receptor (HER2) status, and administration of chemotherapy. The female and male patients were matched 2:1. In this analysis, 316 women and 158 men treated with TAM, and 60 women and 30 men treated with AI, were included. The overall survival (OS) was estimated by the Kaplan-Meier method and was compared between FBC and MBC. TAM-treated FBC and MBC patients had similar 5-year OS, 85.1 and 89.2%, respectively (p = 0.972). Notably, FBC patients treated with AI had significantly greater 5-year OS (85.0%) in comparison with AI-treated MBC patients (5-year OS of 73.3%; p = 0.028). The OS of TAM-treated patients with MBC was similar to the OS of TAM-treated FBC patients, whereas AI treatment is associated with poorer survival of MBC patients.

A 5 year prospective study of patient-relevant outcomes after total knee replacement

DEFF Research Database (Denmark)

Nilsdotter, A-K; Toksvig-Larsen, S; Roos, E M

2008-01-01

men, mean age 71 (51-86) assigned for TKR at the Department of Orthopaedics at Lund University Hospital were included in the study. The self-administered questionnaires Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were mailed preoperatively and 6 months, 12 months and at 5 years......OBJECTIVE: To prospectively describe self-reported outcomes up to 5 years after total knee replacement (TKR) in Osteoarthritis (OA) and to study which patient-relevant factors may predict outcomes for pain and physical function (PF). METHODS: 102 consecutive patients with knee OA, 63 women and 39...... postoperatively. RESULTS: Response rate at 5 years was 86%. At 6 months significant improvement was seen in all KOOS and SF-36 scores (P

Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines.

Science.gov (United States)

Attia, Yasmin M; El-Abhar, Hanan S; Al Marzabani, Mahmoud M; Shouman, Samia A

2015-11-03

Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines

International Nuclear Information System (INIS)

Attia, Yasmin M.; EL-Abhar, Hanan S.; Al Marzabani, Mahmoud M.; Shouman, Samia A.

2015-01-01

Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment

Effects of liarozole fumarate (R85246) in combination with tamoxifen on N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma and uterus in the rat model

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Goss, Paul E; Strasser-Weippl, Kathrin; Qi, Shangle; Hu, Haiqing

2007-01-01

Liarozole fumarate (liarozole – R85246) is a novel compound with characteristics of both aromatase inhibitor (AI) and a retinoic acid metabolism blocking agent (RAMBA). Our objective was to determine the effects of liarozole alone or in combination with tamoxifen on the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma model, as well as on the uterus in ovariectomized immature rats. (1) Tumor burden experiments: Animals bearing one or more tumors greater than 10 mm in diameter were treated for 56 consecutive days with 20 mg/kg or 80 mg/kg of liarozole by oral gavage, tamoxifen 100 μg/kg by subcutaneous injection, or a combination of liarozole and tamoxifen. At the end of the treatment period, total cumulative tumor volume as well as retinoic acid levels were measured. (2) Uterotrophic assay and proliferation experiments: 21-day-old ovariectomized (OVX) Sprague-Dawley rats were treated with 20 mg/kg or 80 mg/kg of liarozole by oral gavage, tamoxifen 1 mg/kg by subcutaneous injection, and combination of both for 4 consecutive days. At the end of the treatment period, uterine weight, epithelial lining cell height and indices of proliferation cell nuclear antigen (PCNA) were measured. The tumor burden experiments in rats bearing estrogen receptor (ER) positive mammary tumours showed that liarozole has a marked anti-tumour effect. In combination with tamoxifen, liarozole had neither an additive nor an antagonistic effect. However, liarozole markedly reduced the uterotrophic effects induced by tamoxifen. Liarozole's antitumor effects on ER positive mammary tumors and its protective effect on the uterus merit further studies to confirm its clinical value in combination with tamoxifen in ER positive postmenopausal breast cancer. Liarozole and other retinomimetics might also be suitable chemoprevention drugs in combination with tamoxifen because of their favorable toxicity profile

Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a systematic review

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Kunath Frank

2012-08-01

Full Text Available Abstract Background Tamoxifen has emerged as a potential management option for gynecomastia and breast pain due to non-steroidal antiandrogens, and it is considered an alternative to surgery or radiotherapy. The objective of this systematic review was to assess the benefits and harms of tamoxifen, in comparison to other treatment options, for either the prophylaxis or treatment of breast events induced by non-steroidal antiandrogens in prostate cancer patients. Methods We searched CENTRAL, MEDLINE, EMBASE, reference lists, the abstracts of three major conferences and three trial registers to identify ongoing randomized controlled trials (RCTs. Two authors independently screened the articles identified, assessed the trial quality and extracted data. The protocol was prospectively registered (CRD42011001320; http://www.crd.york.ac.uk/PROSPERO. Results Four studies were identified. Tamoxifen significantly reduced the risk of suffering from gynecomastia (risk ratio 9RR0 0.10, 95% CI 0.05 to 0.22 or breast pain (RR 0.06, 95% CI 0.02 to 0.17 at six months compared to untreated controls. Tamoxifen also showed a significant benefit for the prevention of gynecomastia (RR 0.22, 95% CI 0.08 to 0.58 and breast pain (RR 0.25, 95% CI 0.10 to 0.64 when compared to anastrozole after a median of 12 months. One study showed a significant benefit of tamoxifen for the prevention of gynecomastia (RR 0.24, 95% CI 0.09 to 0.65 and breast pain (RR 0.20, 95% CI 0.06 to 0.65 when compared with radiotherapy at six months. Radiotherapy increased the risk of suffering from nipple erythema and skin irritation, but there were no significant differences for any other adverse events (all P > 0.05. Conclusions The currently available evidence suggests good efficacy of tamoxifen for the prevention and treatment of breast events induced by non-steroidal antiandrogens. The impact of tamoxifen therapy on long-term adverse events, disease progression and survival remains unclear

Side effects associated with ultrarapid cytochrome P450 2D6 genotype among women with early stage breast cancer treated with tamoxifen.

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Rolla, R; Vidali, M; Meola, S; Pollarolo, P; Fanello, M R; Nicolotti, C; Saggia, C; Forti, L; Agostino, F D; Rossi, V; Borra, G; Stratica, F; Alabiso, O; Bellomo, G

2012-01-01

The side effects of tamoxifen, a drug widely used for the treatment and the prevention of recurrence in patients with estrogen receptor positive breast cancers (ER+), have been reported in clinical trials, but to date no information is available on their possible association with an increased enzymatic activity of CYP2D6 (ultra-metabolizers, UMs). The aim of this study was therefore to evaluate the association between the presence of multiple functional CYP2D6 alleles and the occurrence of side effects. 61 women with ER+ breast cancer receiving tamoxifen monotherapy were investigated in order to assess the relationships between CYP2D6 UM phenotype and side effects. Genotyping of 16 CYP2D6 polymorphisms was performed using a new DNA microarray technology. A highly significant difference was detected (41.2% of difference, 95% CI 6 - 61%, Fisher's exact test, p = 0.030) between the numbers of Ultrarapid Metabolizer patients (UM; high activity) with two or more adverse drug reactions to tamoxifen (7/9; 77.8%), compared to the number of Extensive Metabolizers (EM; normal activity), Intermediate Metabolizers (IM; reduced activity), and Poor Metabolizers (PM; no activity) with at least two side effects (19/52, 36.5%). A similar difference was also observed comparing the two groups (UM vs EM-IM-PM) for the number of side effects (median and inter quartile range, IQR: AM/EM/IM 1, IQR 0-2 vs. ULTRA 2, IQR 2-4; Mann-Whitney p = 0.005). Our results suggest a new association between CYP2D6 gene duplication and side effects to tamoxifen, indicating a possible role of CYP2D6 in their occurrence.

Postoperative chemoradiotherapy in high risk locally advanced gastric cancer

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Song, Sang Hyuk; Chie, Eui Kyu; Kim, Kyu Bo; Lee, Hyuk Joon; Yang, Han Kwang; Han, Sae Won; Oh, Do Youn; Im, Seok Ah; Bang, Yung Jue; Ha, Sung W. [Seoul National University College of Medicine, Seoul(Korea, Republic of)

2012-12-15

To evaluate treatment outcome of patients with high risk locally advanced gastric cancer after postoperative chemoradiotherapy. Between May 2003 and May 2012, thirteen patients who underwent postoperative chemoradiotherapy for gastric cancer with resection margin involvement or adjacent structure invasion were retrospectively analyzed. Concurrent chemotherapy was administered in 10 patients. Median dose of radiation was 50.4 Gy (range, 45 to 55.8 Gy). The median follow-up duration for surviving patients was 48 months (range, 5 to 108 months). The 5-year overall survival rate was 42% and the 5-year disease-free survival rate was 28%. Major pattern of failure was peritoneal seeding with 46%. Loco-regional recurrence was reported in only one patient. Grade 2 or higher gastrointestinal toxicity occurred in 54% of the patients. However, there was only one patient with higher than grade 3 toxicity. Despite reported suggested role of adjuvant radiotherapy with combination chemotherapy in gastric cancer, only very small portion of the patients underwent the treatment. Results from this study show that postoperative chemoradiotherapy provided excellent locoregional control with acceptable and manageable treatment related toxicity in patients with high risk locally advanced gastric cancer. Thus, postoperative chemoradiotherapy may improve treatment result in terms of locoregional control in these high risk patients. However, as these findings are based on small series, validation with larger cohort is suggested.

Tamoxifen Promotes Axonal Preservation and Gait Locomotion Recovery after Spinal Cord Injury in Cats

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Braniff de la Torre Valdovinos

2016-01-01

Full Text Available We performed experiments in cats with a spinal cord penetrating hemisection at T13-L1 level, with and without tamoxifen treatment. The results showed that the numbers of the ipsilateral and contralateral ventral horn neurons were reduced to less than half in the nontreated animals compared with the treated ones. Also, axons myelin sheet was preserved to almost normal values in treated cats. On the contrary, in the untreated animals, their myelin sheet was reduced to 28% at 30 days after injury (DAI, in both the ipsilateral and contralateral regions of the spinal cord. Additionally, we made hindlimb kinematics experiments to study the effects of tamoxifen on cat locomotion after the injury: at 4, 16, and 30 DAI. We observed that the ipsilateral hindlimb angular displacement (AD of the pendulum-like movements (PLM during gait locomotion was recovered to almost normal values in treated cats. Contralateral PLM acquired similar values to those obtained in intact cats. At 4 DAI, untreated animals showed a compensatory increment of PLM occurring in the contralateral hindlimb, which was partially recovered at 30 DAI. Our findings indicate that tamoxifen exerts a neuroprotective effect and preserves or produces myelinated axons, which could benefit the locomotion recovery in injured cats.

Postoperative radiation therapy for major salivary gland cancer

International Nuclear Information System (INIS)

Kato, Fumio; Yahara, Katsuya; Ohguri, Takayuki

2003-01-01

A retrospective study was performed on 29 patients with major salivary gland cancer treated with postoperative irradiation between 1981 and 2002. Univariate and multivariate analyses of age, gender, cancer grade, T stage, N stage, surgical resectability, concomitant chemotherapy, and neoadjuvant or adjuvant chemotherapy were performed for disease-free survival. The 5-year survival rates and 5-year disease-free survival rate were 61.6% and 41.4%, respectively. Both univariate and multivariate analyses showed that cancer grade and surgical resectability influenced survival rates. Chemotherapy did not influence the disease-free survival. The total dose of postoperative radiation was 47.6±8.8 Gy in the complete excision group as planned, but was 56.1±7.9 Gy in the incomplete excision group, which may be insufficient and lead to poor treatment outcome. (author)

The Possible Effect Of Tamoxifen Vs Whole Body Irradiation Treatment On Thyroid Hormones in Female Rats Bearing Mammary Tumors Chemically Induced

International Nuclear Information System (INIS)

Abdelgawad, M.R.

2012-01-01

Breast cancer is the most common malignancy among women in most developed and developing regions of the world. In women, this drug has tissuespecific effects, acting as an estrogen antagonist on the breast, and as an estrogen agonist on bone, lipid metabolism (increasing high-density lipoprotein cholesterol and decreasing low-density lipoprotein cholesterol), and the endometrium. Thyroid hormones act on almost all organs throughout the body and regulate the basal metabolism of the organism. Thyroid hormone can also stimulate the proliferation in vitro of certain tumor cell lines. The aim of the present study is to evaluate the significant value of tamoxifen and/or irradiation treatment on thyroid hormones in breast cancer bearing female rats. Forty two female Sprague-Dawely rats randomly divided into seven groups and the effect of tamoxifen and post-irradiation was studied on breast cancer chemically induced. The results shows a T 4 and estradiol levels not T 3 were altered in different experimental groups. It could be concluded that irradiation-induced changes in the composition of the mammary microenvironment promote the expression of neoplastic potential by affecting both estradiol and thyroid hormones, and tamoxifen may alter the thyroid hormones. Irradiation and tamoxifen administration may have worth effects on T 4 and estradiol levels and it is recommended to further studies towards the bystander effect of radiation and tamoxifen on the tissue culture and molecular biology scale.

EARLY POSTOPERATIVE COMPLICATIONS AFTER RADICAL CYSTECTOMY

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V. O. Mager

2014-08-01

Full Text Available Radical cystectomy (RCE is associated with a considerable number of early postoperative complications as before. Based on 10 years’ experience, this paper demonstrates the frequency (33.9 % and types of early complications following RCE, as well as postoperative mortality (5.5 % and its resulting causes. Although postoperative mortality is relatively low today, the frequency of early postoperative complications remains high as before.

SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION: EARLY POSTOPERATIVE COMPLICATIONS

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M.Sh. Khubutia

2014-01-01

Full Text Available Aim: evaluation of the incidence of early postoperative complications after simultaneous pancreas-kidney transplantation.Materials and methods. The analysis of early postoperative complications after simultaneous pancreas-kidney transplantation is presented in the paper, the most rational diagnostic algorithms, non-surgical and surgical complications’ treatment; the outcomes of the SPKT are reported.Results. 15,6% of patients experienced surgical complications, 12,5% – immunological complications, 12,5% – infectious complications, 6,25% – complications of the immunosuppressive therapy. 1-year patient survival after SPKT was 91,4%; pancreas graft survival – 85,7%; kidney graft survival – 88,6%.Conclusion. The incidence of early postoperative complications after simultaneous pancreas-kidney transplantation remains signifi cant in spite of progressive improvement of simultaneous pancreas-kidney transplantation due to surgical technique improvement, introduction of new antibacterial and immunosuppressive agents. Data, we recovered, fully correspond to the data obtained from the global medical community.

[Postoperative complications and survival analysis of 1 118 cases of open splenectomy and azygoportal disconnection in the treatment of portal hypertension].

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Qi, R Z; Zhao, X; Wang, S Z; Zhang, K; Chang, Z Y; Hu, X L; Wu, M L; Zhang, P R; Yu, L X; Xiao, C H; Shi, X J; Li, Z W

2018-06-01

Objective: To analyze the recent postoperative and long-term postoperative complications of open-splenectomy and disconnection in patients with portal hypertension. Methods: There were 1 118 cases with portal hypertension who underwent open splenectomy and azygoportal disconnection from April 2010 to September 2015 at Department of Surgery, People's Liberation Army 302 Hospital. Retrospective case investigation and telephone follow-up were conducted in October 2016. All patients had history of upper gastrointestinal bleeding before operation. Short-term complications after surgery were recorded including secondary laparotomy of postoperative abdominal hemostasis, severe infection, intake disorders, liver insufficiency, postoperative portal vein thrombosis and perioperative mortality. Long-term data including postoperative upper gastrointestinal rebleeding, postoperative survival rate and incidence of postoperative malignancy were recorded, too. GraphPad Prism 5 software for data survival analysis and charting. Results: Postoperative short-term complications in 1 118 patients included secondary laparotomy of postoperative abdominal hemostasis(1.8%, 21/1 118), severe infection(2.9%, 32/1 118), intake disorders(1.0%, 11/1 118), liver dysfunction (1.6%, 18/1 118), postoperative portal vein thrombosis(47.1%, 526/1 118)and perioperative mortality(0.5%, 5/1 118). After phone call following-up, 942 patients' long-term data were completed including 1, 3, 5 years postoperative upper gastrointestinal rebleeding rate(4.4%, 12.1%, 17.2%), 1, 3, 5-year postoperative survival rate(97.0%, 93.5%, 90.3%); the incidence of postoperative malignant tumors in 1, 3 and 5 years were 1.7%, 4.4% and 6.2%. Conclusions: Reasonable choosing of surgical indications and timing, proper performing the surgery process, effective conducting perioperative management of portal hypertension are directly related to the patient's short-term prognosis after portal hypertension. Surgical intervention can

Postoperative Radiation Therapy of Craniopharyngioma

International Nuclear Information System (INIS)

Shin, Kyung Hwan; Kim, Il Han; Park, Charn Il; Cho, Byung Kyu; Yun, Hyong Geln

1993-01-01

Between December 1979 and September 1989, 23 patients with craniopharyngioma who underwent surgery and postoperative radiation therapy were retrospectively evaluated to assess the efficacy of this management at the Department of Therapeutic Radiology, Seoul National University Hospital. Total removal of tumor was attempted in all patients. Of these, surgeons tried total removal in eight patients, but revealed residual mass by postoperative CT, and partial removal was done in 15 patients. The morphology of tumor on the operative finding was grouped into three types : cystic 13 (57%), solid 4 (17%), and mixed 6 (26%). Cystic type was predominant in ≤20 years old group. Actuarial overall survival rates at 5 and 10 years were 95% and 81% respectively and actuarial tumor control rates were 74% and 50%. Surgical extent was not related to the survival rates(p=0.41). Pediatric and adolescent Patients(age of ≤20 year) had a trend of better survival than that of adult patients(p=0.10). The results indicated that limited surgical excision followed by radiation therapy is recommended when total excision is not possible

Postoperative Radiation Therapy of Craniopharyngioma

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Shin, Kyung Hwan; Kim, Il Han; Park, Charn Il; Cho, Byung Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of); Yun, Hyong Geln [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1993-06-15

Between December 1979 and September 1989, 23 patients with craniopharyngioma who underwent surgery and postoperative radiation therapy were retrospectively evaluated to assess the efficacy of this management at the Department of Therapeutic Radiology, Seoul National University Hospital. Total removal of tumor was attempted in all patients. Of these, surgeons tried total removal in eight patients, but revealed residual mass by postoperative CT, and partial removal was done in 15 patients. The morphology of tumor on the operative finding was grouped into three types : cystic 13 (57%), solid 4 (17%), and mixed 6 (26%). Cystic type was predominant in {<=}20 years old group. Actuarial overall survival rates at 5 and 10 years were 95% and 81% respectively and actuarial tumor control rates were 74% and 50%. Surgical extent was not related to the survival rates(p=0.41). Pediatric and adolescent Patients(age of {<=}20 year) had a trend of better survival than that of adult patients(p=0.10). The results indicated that limited surgical excision followed by radiation therapy is recommended when total excision is not possible.

Management of stage III thymoma with postoperative radiation therapy

International Nuclear Information System (INIS)

Krueger, J.B.; Sagerman, R.H.; King, G.A.

1987-01-01

The results of postoperative radiation therapy in 12 patients with Stage III thymoma treated during the period 1966-1986 were reviewed. Surgical therapy consisted of total resection in one, subtotal resection in seven, and biopsy only in four. Megavoltage irradiation in the dose range of 3,000-5,600 cGy was employed, with the majority receiving a dose of at least 5,000 cGy. The local control rate was 67%. The actuarial 5-year observed and adjusted survival rates were 57% and 75%, respectively. These results indicate that postoperative radiation therapy is an effective therapeutic modality in the control of Stage III thymoma

Antiproliferation and apoptosis induced by tamoxifen in human bile duct carcinoma QBC939 cells via upregulated p53 expression

International Nuclear Information System (INIS)

Han, Peng; Kang, Jin-He; Li, Hua-Liang; Hu, Su-Xian; Lian, Hui-Hui; Qiu, Ping-Ping; Zhang, Jian; Li, Wen-Gang; Chen, Qing-Xi

2009-01-01

Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been used in the treatment of breast cancer for over 30 years. Recently, it was shown that TAM also has efficacy on gastrointestinal neoplasms such as hepatocarcinoma and pancreatic carcinoma, and that the chemopreventive activities of TAM might be due to its abilities to inhibit cell growth and induce apoptosis. In the present study, we investigated the effects of tamoxifen on growth and apoptosis in the human bile duct carcinoma (BDC) cell line QBC939 using MTT assay, inverted microscopy, fluorescence microscopy, transmission electron microscopy, classic DNA fragmentation agarose gel electrophoresis assay, PI single- and FITC/PI double-staining flow cytometry, and Western blotting. Our data revealed that TAM could significantly inhibit growth and induce apoptosis in QBC939 cells. Increased expression of p53 was observed in TAM-treated cells, indicating that p53 might play an important role in TAM-induced apoptosis in QBC939 cells. These results provide significant insight into the anticarcinogenic action of TAM on BDC.

Antiproliferation and apoptosis induced by tamoxifen in human bile duct carcinoma QBC939 cells via upregulated p53 expression

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Han, Peng; Kang, Jin-He; Li, Hua-Liang [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Hu, Su-Xian [First Hospital Attached to Fujian Medical University, Xiamen 361004 (China); Lian, Hui-Hui; Qiu, Ping-Ping; Zhang, Jian [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Li, Wen-Gang [First Hospital Attached to Fujian Medical University, Xiamen 361004 (China); Chen, Qing-Xi [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen 361005 (China)

2009-07-24

Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been used in the treatment of breast cancer for over 30 years. Recently, it was shown that TAM also has efficacy on gastrointestinal neoplasms such as hepatocarcinoma and pancreatic carcinoma, and that the chemopreventive activities of TAM might be due to its abilities to inhibit cell growth and induce apoptosis. In the present study, we investigated the effects of tamoxifen on growth and apoptosis in the human bile duct carcinoma (BDC) cell line QBC939 using MTT assay, inverted microscopy, fluorescence microscopy, transmission electron microscopy, classic DNA fragmentation agarose gel electrophoresis assay, PI single- and FITC/PI double-staining flow cytometry, and Western blotting. Our data revealed that TAM could significantly inhibit growth and induce apoptosis in QBC939 cells. Increased expression of p53 was observed in TAM-treated cells, indicating that p53 might play an important role in TAM-induced apoptosis in QBC939 cells. These results provide significant insight into the anticarcinogenic action of TAM on BDC.

Postoperative radiotherapy for malignant tumors of the submandibular gland

International Nuclear Information System (INIS)

Storey, Mark R.; Garden, Adam S.; Morrison, William H.; Eicher, Susan A.; Schechter, Naomi R.; Ang, K. Kian

2001-01-01

Purpose: This retrospective study assessed the outcome and patterns of failure for patients with malignant submandibular tumors treated with surgery and postoperative radiation. Methods and Materials: Between 1965 and 1995, 83 patients aged 11-83 years old received postoperative radiotherapy after resection of submandibular gland carcinomas. The most common radiation technique was an appositional field to the submandibular gland bed using electrons either alone or mixed with photons. Primary tumor bed doses ranged from 50 to 69 Gy (median, 60 Gy). Regional lymph nodes (ipsilateral Levels I-IV) were irradiated in 66 patients to a median dose of 50 Gy. Follow-up time ranged from 5 to 321 months (median, 82 months). Results: Actuarial locoregional control rates were 90%, 88%, and 88% at 2, 5, and 10 years, respectively. The corresponding disease-free survival rates were 76%, 60%, and 53%, because 27 of 74 patients (36%) who attained locoregional control developed distant metastases. Adenocarcinoma, high-grade histology, and treatment during the earlier years of the study were associated with worse locoregional control and disease-free survival. The median survival times for patients with and without locoregional control were 183 months and 19 months, respectively. Actuarial 2-, 5-, and 10-year survival rates were 84%, 71%, and 55%, respectively. Late complications occurred in 8 patients (osteoradionecrosis, 5 patients). Conclusions: High-risk cancers of the submandibular gland have a historic control rate of approximately 50% when treated with surgery alone. In the current series, locoregional control rates for high-risk patients with submandibular gland cancers treated with surgery and postoperative radiotherapy were excellent, with an actuarial locoregional control rate of 88% at 10 years

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

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Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Postoperative radiotherapy for stage II and III rectal cancer

International Nuclear Information System (INIS)

Qian Liting; Song Yongwen; Liu Xinfan; Yu Zihao; Qian Tunan; Li Yexiong

2003-01-01

Objective: To evaluate the impact of postoperative adjuvant radiotherapy, compared with surgery alone for rectal cancer. Methods: From January 1994 to October 1997, 192 patients with stage II or III rectal cancer were treated by radical resection and postoperative radiotherapy (Group S + R) and 51 patients with the same stage lesions underwent surgery alone (Group S). The median dose of radiation was 50(32-62) Gy. Kaplan-Meier method and Log-rank test were used for analysis. Results: The 5-year overall and disease-free survival rates were 60.3% and 58.3%, respectively. The overall 5-year survival rate was 59.4% in Group S + R and 64.7% in Group S, and the 5-year disease-free survival rates were 57.0% and 66.4%, respectively. There were no significant differences between either group (P=0.601 and P=0.424). The disease-free survival was not significantly prolonged in Group S + R as compared with that of Group S. The local recurrence rate was evidently reduced in Group S + R (15.8% v 26.8%, P=0.043). Conclusion: Local recurrence is a major cause of morbidity and mortality in rectal cancer. Postoperative radiotherapy, though reduces the incidence of local recurrence, does not improve the survival in the treatment of stage II and III diseases

The biochemical effects of nano tamoxifen and some bioactive components in experimental breast cancer.

Science.gov (United States)

Ezzat, Afaf; Abdelhamid, Abdou Osman; El Awady, Mostafa K; Abd El Azeem, Amal S; Mohammed, Dina Mostafa

2017-11-01

The effect of nano tamoxifen and some bioactive components such as yeast, isoflavone, and silymarin on the level of resistance and prevention of breast cancer progression in experimental animals is the target of this study. Thirty female Sprague-Dawley rats received a single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) intragastrically. After fourteen days of DMBA admission, the procedure protocol started out. Finally, all the experimental results evaluated, tabulated and statistically analyzed. The results demonstrated a highly significant elevation in the 8-OHdG level in group 1 (nano yeast) and 3 (nano silymarin) while the results demonstrated a highly significant reduction in group 2 (nano tamoxifen). The apoptosis results demonstrated a significant elevation in group 3 (nano silymarin) where appeared significant reduction in group 4 (nano isoflavone). ErbB-2 results demonstrated a significant elevation in group 2 (nano tamoxifen) and a significant reduction in each of group 3 (nano silymarin) and 4 (nano isoflavone). The lipid peroxide level demonstrated an extremely significant reduction in group 4 (nano isoflavone). And a significant reduction of total antioxidant was observed in group 3 (nano silymarin) in comparison to injected animals control. This may be considered a new vision and strategy to resist breast cancer disease or prevent progression. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Alcohol screening and risk of postoperative complications in male VA patients undergoing major non-cardiac surgery.

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Bradley, Katharine A; Rubinsky, Anna D; Sun, Haili; Bryson, Chris L; Bishop, Michael J; Blough, David K; Henderson, William G; Maynard, Charles; Hawn, Mary T; Tønnesen, Hanne; Hughes, Grant; Beste, Lauren A; Harris, Alex H S; Hawkins, Eric J; Houston, Thomas K; Kivlahan, Daniel R

2011-02-01

Patients who misuse alcohol are at increased risk for surgical complications. Four weeks of preoperative abstinence decreases the risk of complications, but practical approaches for early preoperative identification of alcohol misuse are needed. To evaluate whether results of alcohol screening with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) questionnaire-up to a year before surgery-were associated with the risk of postoperative complications. This is a cohort study. Male Veterans Affairs (VA) patients were eligible if they had major noncardiac surgery assessed by the VA's Surgical Quality Improvement Program (VASQIP) in fiscal years 2004-2006, and completed the AUDIT-C alcohol screening questionnaire (0-12 points) on a mailed survey within 1 year before surgery. One or more postoperative complication(s) within 30 days of surgery based on VASQIP nurse medical record reviews. Among 9,176 eligible men, 16.3% screened positive for alcohol misuse with AUDIT-C scores ≥ 5, and 7.8% had postoperative complications. Patients with AUDIT-C scores ≥ 5 were at significantly increased risk for postoperative complications, compared to patients who drank less. In analyses adjusted for age, smoking, and days from screening to surgery, the estimated prevalence of postoperative complications increased from 5.6% (95% CI 4.8-6.6%) in patients with AUDIT-C scores 1-4, to 7.9% (6.3-9.7%) in patients with AUDIT-Cs 5-8, 9.7% (6.6-14.1%) in patients with AUDIT-Cs 9-10 and 14.0% (8.9-21.3%) in patients with AUDIT-Cs 11-12. In fully-adjusted analyses that included preoperative covariates potentially in the causal pathway between alcohol misuse and complications, the estimated prevalence of postoperative complications increased significantly from 4.8% (4.1-5.7%) in patients with AUDIT-C scores 1-4, to 6.9% (5.5-8.7%) in patients with AUDIT-Cs 5-8 and 7.5% (5.0-11.3%) among those with AUDIT-Cs 9-10. AUDIT-C scores of 5 or more up to a year before surgery were

Generation of NSE-MerCreMer transgenic mice with tamoxifen inducible Cre activity in neurons.

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Mandy Ka Man Kam

Full Text Available To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer, which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult.

[Effect evaluation of over 5 year follow up of unilateral pedicle screw fixation with transforaminal lumbar interbody fusion for lumbar degenerative diseases].

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Wang, Chong; Ying, Jin-He; Xie, Pan-Pan; Wu, Xiao-Guang

2016-07-25

To evaluate the clinical effects of over 5 year follow up of unilateral pedicle screw fixation with transforaminal lumbar interbody fusion(TLIF) in treating lumbar degenerative diseases. The clinical data of 24 patients with lumbar degenerative disease underwent unilateral pedicle screw fixation with transforaminal lumbar interbody fusion from March 2007 to October 2009, were retrospectively analyzed. There were 13 males and 11 females, aged from 34 to 68 years old with an average of 52 years. Postoperative pain and functional results were analyzed by the visual analogue scale(VAS) and Oswestry Disability Index(ODI). Radiological examination was obtained for each patient to assess the height of intervertebral space, postoperative intervertebral fusion conditions and general complications. All patients were followed up from 5 to 8 years with an average of 6.7 years. VAS scores of low back pain and leg pain decreased from preoperative 7.82±0.71, 8.42±1.24 to postoperative 1.87±0.81, 2.23±1.62, respectively( P degenerative diseases according to over 5 year follow up, however, its indications should be well considered. But the problems such as intervertebral space height of operated side loss and adjacent segment degeneration after unilateral pedicle screw fixation need further clinical study.

Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes.

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Bi, Xiu-Zeng; Pan, Wei-Hua; Yu, Xin-Ping; Song, Zong-Ming; Ren, Zeng-Jin; Sun, Min; Li, Cong-Hui; Nan, Kai-Hui

2015-01-01

This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 μg/ml over three months in vitro. Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33-8.67 mmHg, whereas that of group C gradually remained at 7.55-10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.

A journey to zero: reduction of post-operative cesarean surgical site infections over a five-year period.

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Hickson, Evelyn; Harris, Jeanette; Brett, David

2015-04-01

Surgical site infections (SSI) are a substantial concern for cesarean deliveries in which a surgical site complication is most unwelcome for a mother with a new infant. Steps taken pre- and post-operatively to reduce the number of complications may be of substantial benefit clinically, economically, and psychologically. A risk-based approach to incision management was developed and implemented for all cesarean deliveries at our institution. A number of incremental interventions for low-risk and high-risk patients including pre-operative skin preparations, standardized pre- and post-operative protocols, post-operative nanocrystalline silver anti-microbial barrier dressings, and incisional negative pressure wound therapy (NPWT) were implemented sequentially over a 5-y period. A systematic clinical chart review of 4,942 patients spanning all cesarean deliveries between 2007-2012 was performed to determine what effects the interventions had on the rate of SSI for cesarean deliveries. The percentage of SSI was reduced from 2.13% (2007) to 0.10% (2012) (poperative SSIs were avoided: A total cost saving of nearly $5,000,000. Applying a clinical algorithm for assessing the risk of surgical site complication and making recommendations on pre-operative and post-operative incision management can result in a substantial and sustainable reduction in cesarean SSI.

A retrospective analysis of the postoperative use of loteprednol etabonate gel 0.5% following laser-assisted in situ keratomileusis or photorefractive keratectomy surgery

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Salinger CL

2015-11-01

Full Text Available Clifford L Salinger,1 Michael Gordon,2 Mitchell A Jackson,3 Theodore Perl,4 Eric Donnenfeld5 1VIP Laser Eye Center, Palm Beach Gardens, FL, 2Gordon Weiss Schanzlin Vision Institute, San Diego, CA, 3Jacksoneye, Lake Villa, IL, 4Corneal Associates of New Jersey, Fairfield, NJ, 5Ophthalmic Consultants of Long Island, Garden City, NY, USA Background: While loteprednol etabonate ophthalmic gel 0.5% (LE gel is approved for treatment of postoperative ocular inflammation and pain, there have been no reported studies in patients undergoing laser-assisted in situ keratomileusis (LASIK or photorefractive keratectomy (PRK.Methods: This was a retrospective chart review conducted at five refractive surgical centers in the USA. Data were collected from primary LASIK or PRK surgery cases in which LE gel was used postoperatively as the clinician’s routine standard of care and in which patients were followed-up for up to 6 months. Data extracted from charts included patient demographics, surgical details, LE gel dosing regimen, pre- and postsurgical refractive characteristics, intraocular pressure (IOP measurements, and visual acuity. Primary outcomes included postoperative IOP elevations, adverse events, and early discontinuations.Results: Data were collected on 189 LASIK eyes (96 patients and 209 PRK eyes (108 patients. Mean (standard deviation [SD] years of age at surgery was 36.0 (11.7 and 33.9 (11.3 in LASIK and PRK patients. LE gel was prescribed most often four times daily during the first postoperative week, regardless of procedure; the most common treatment duration was 7–14 days in LASIK and ≥30 days in PRK patients. No unusual corneal findings or healing abnormalities were reported. Mean postoperative uncorrected distance visual acuity was 20/24 in LASIK and 20/30 in PRK eyes. Mild/trace corneal haze was reported in 20% of PRK patients; two PRK patients with moderate/severe corneal haze were switched to another corticosteroid. Mean postoperative

A tamoxifen inducible knock-in allele for investigation of E2A function

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Kondo Motonari

2009-10-01

Full Text Available Abstract Background E-proteins are transcription factors important for the development of a variety of cell types, including neural, muscle and lymphocytes of the immune system. E2A, the best characterized E-protein family member in mammals, has been shown to have stage specific roles in cell differentiation, lineage commitment, proliferation, and survival. However, due to the complexity of E2A function, it is often difficult to separate these roles using conventional genetic approaches. Here, we have developed a new genetic model for reversible control of E2A protein activity at physiological levels. This system was created by inserting a tamoxifen-responsive region of the estrogen receptor (ER at the carboxyl end of the tcfe2a gene to generate E2AER fusion proteins. We have characterized and analyzed the efficiency and kinetics of this inducible E2AER system in the context of B cell development. Results B cell development has been shown previously to be blocked at an early stage in E2A deficient animals. Our E2AER/ER mice demonstrated this predicted block in B cell development, and E2AER DNA binding activity was not detected in the absence of ligand. In vitro studies verified rapid induction of E2AER DNA binding activity upon tamoxifen treatment. While tamoxifen treatment of E2AER/ER mice showed inefficient rescue of B cell development in live animals, direct exposure of bone marrow cells to tamoxifen in an ex vivo culture was sufficient to rescue and support early B cell development from the pre-proB cell stage. Conclusion The E2AER system provides inducible and reversible regulation of E2A function at the protein level. Many previous studies have utilized over-expression systems to induce E2A function, which are complicated by the toxicity often resulting from high levels of E2A. The E2AER model instead restores E2A activity at an endogenous level and in addition, allows for tight regulation of the timing of induction. These features make

Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen

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Anna Benedykcinska

2016-02-01

Full Text Available Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS can be limited, when the promoter (such as GFAP is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours.

Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen.

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Benedykcinska, Anna; Ferreira, Andreia; Lau, Joanne; Broni, Jessica; Richard-Loendt, Angela; Henriquez, Nico V; Brandner, Sebastian

2016-02-01

Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS) can be limited, when the promoter (such as GFAP) is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER) allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours. © 2016. Published by The Company of Biologists Ltd.

Tamoxifen added to radiotherapy and surgery for the treatment of ductal carcinoma in situ of the breast: A meta-analysis of 2 randomized trials

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Petrelli, Fausto; Barni, Sandro

2011-01-01

Background: Surgical excision with adequate margins is the treatment of choice for ductal, in situ carcinoma of the breast (DCIS). The addition of radiotherapy (RT) halved local in situ and invasive recurrence. The purpose of our meta-analysis is to evaluate the reduction in recurrence (in situ or invasive) with the addition of tamoxifen (T), in particular in patients with DCIS treated with surgery + RT. Patients and methods: The eligible studies (NSABP-B24 and UK ANZ DCIS trials) included prospective, randomized, controlled trials in which the addition of T had been compared with surgery + RT without T in women with DCIS of the breast. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated for both in situ and invasive recurrence (local and controlateral). Results: Tamoxifen does not reduce breast cancer-specific or overall mortality when added to loco-regional therapy for DCIS of the breast (surgery plus or minus RT). Tamoxifen reduces overall breast cancer recurrence by 29% in all patients and by 33% in those treated with both surgery and RT. Only ipsilateral invasive (RR 0.61 [95% CI 0.41, 0.92]; p = 0.02) and controlateral in situ relapses (RR 0.40 [95% CI 0.16, 0.96]; p = 0.04) are significantly lowered when T is added to RT. Tamoxifen seems to exert a local synergistic effect with RT. Both young and older women ( 50 years) achieve some benefit from the addition of T (RR 0.6 and 0.74, respectively). Conclusion: The addition of T to surgery and RT for DCIS of the breast reduces the risk of local invasive and controlateral in situ relapses, but not the survival. The benefit is independent of age. In conclusion, surgery associated with RT and T is the treatment of choice for patients with (estrogen-receptor positive) DCIS of the breast.

Post-operative pain following coblation or monopolar electrocautery tonsillectomy in children: a prospective, single-blinded, randomised comparison.

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Parker, N P; Walner, D L

2011-10-01

To compare post-operative pain following tonsillectomy by either coblation or monopolar electrocautery in children. A parallel-designed, prospective, single-blinded, randomised trial. Ambulatory surgical facility. Eighty otherwise healthy paediatric patients undergoing coblation or electrocautery tonsillectomy by a fellowship-trained paediatric otolaryngologist. (i) The number of post-operative days with severe pain based on subjective qualification by the caretaker, (ii) post-operative days with pain rated ≥ 5 on a scale of 1-10, (iii) post-operative days requiring oral paracetamol/acetaminophen with codeine solution and (iv) post-operative days until resumption of a regular diet were assessed and recorded daily using a post-operative pain survey as a form of daily diary that was returned at the 2-week follow-up visit. Patients were consecutively enrolled into two groups of 40 patients. Average ages were 5.2 years for coblation tonsillectomy and 6.0 years for electrocautery tonsillectomy. The average number of post-operative days with severe pain was 4.2 for coblation and 5.9 for electrocautery (P = 0.006), days rating pain ≥ 5 were 3.6 for coblation and 4.8 for electrocautery (P = 0.037), days of codeine use were 2.5 for coblation and 2.9 for electrocautery (P = 0.324), and days until resumption of a regular diet were 5.2 for coblation and 6.2 for electrocautery (0.329). Coblation tonsillectomy may reduce post-operative pain and the time until resumption of a regular diet compared to electrocautery tonsillectomy. © 2011 Blackwell Publishing Ltd.

Identification of risk factors for postoperative dysphagia after primary anti-reflux surgery.

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Tsuboi, Kazuto; Lee, Tommy H; Legner, András; Yano, Fumiaki; Dworak, Thomas; Mittal, Sumeet K

2011-03-01

Transient postoperative dysphagia is not uncommon after antireflux surgery and usually runs a self-limiting course. However, a subset of patients report long-term dysphagia. The purpose of this study was to determine the risk factors for persistent postoperative dysphagia at 1 year after surgery. All patients who underwent antireflux surgery were entered into a prospectively maintained database. After obtaining institutional review board approval, the database was queried to identify patients who underwent primary antireflux surgery and were at least 1 year from surgery. Postoperative severity of dysphagia was evaluated using a standardized questionnaire (scale 0-3). Patients with scores of 2 or 3 were defined as having significant dysphagia. A total of 316 consecutive patients underwent primary antireflux surgery by a single surgeon. Of these, 219 patients had 1 year postoperative symptom data. Significant postoperative dysphagia at 1 year was reported by 19 (9.1%) patients. Thirty-eight patients (18.3%) required postoperative dilation for dysphagia. Multivariate logistic regression analysis identified preoperative dysphagia (odds ratio (OR), 4.4; 95% confidence interval (CI), 1.2-15.5; p = 0.023) and preoperative delayed esophageal transit by barium swallow (OR, 8.2; 95% CI, 1.6-42.2; p = 0.012) as risk factors for postoperative dysphagia. Female gender was a risk factor for requiring dilation during the early postoperative period (OR, 3.6; 95% CI, 1.3-10.2; p = 0.016). No correlations were found with preoperative manometry. There also was no correlation between a need for early dilation and persistent dysphagia at 1 year of follow-up (p = 0.109). Patients with preoperative dysphagia and delayed esophageal transit on preoperative contrast study were significantly more likely to report moderate to severe postoperative dysphagia 1 year after antireflux surgery. This study confirms that the manometric criteria used to define esophageal dysmotility are not reliable

CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence

DEFF Research Database (Denmark)

Damkier, Per; Kjaersgaard, Anders; Barker, Kimberly A.

2017-01-01

*17 allele were 1.02 (CI 0.71-1.46) and 0.57 (CI 0.26-1.24), respectively. Accounting for CYP2D6 genotype status did not change these estimates. We found no evidence to support a clinically meaningful role of CYP2C19 polymorphisms and response to tamoxifen in breast cancer patients and, consequently, CYP2C19...... genotype status should not be included in clinical decisions on tamoxifen treatment....

The distribution pattern of ERα expression, ESR1 genetic variation and expression of growth factor receptors: association with breast cancer prognosis in Russian patients treated with adjuvant tamoxifen.

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Babyshkina, Nataliya; Vtorushin, Sergey; Zavyalova, Marina; Patalyak, Stanislav; Dronova, Tatyana; Litviakov, Nikolay; Slonimskaya, Elena; Kzhyshkowska, Julia; Cherdyntseva, Nadejda; Choynzonov, Evgeny

2017-08-01

Identification of additional biomarkers associated with ER genomic and nongenomic pathways could be very useful to distinguish patients who will benefit from tamoxifen treatment. The aim of this study was to analyze the prognostic significance of the distribution pattern of ERα expression, ESR1 gene single-nucleotide polymorphisms and expression levels of growth factor receptors in Russian hormone receptor-positive breast cancer patients treated with adjuvant tamoxifen. Formalin-fixed paraffin-embedded tumor tissue samples from 97 patients were examined for the distribution pattern of ERα expression, as well as for EGFR and TGF-βR1 expression by immunohistochemistry. Genotypes for ESR1 +30T>C (rs2077647) and ESR1 2014G>A (rs2228480) were analyzed using a TaqMan assay. Progression-free survival (PFS) was used as an endpoint for the survival analyses. We found that patients with the heterogeneous distribution of ERα expression had poor prognosis on tamoxifen treatment (P = 0.021). We identified a high EGFR expression in patients who developed distant metastasis or recurrence during tamoxifen treatment (a tamoxifen-resistant group-TR) in contrast to the distant metastasis-free patients (a tamoxifen-sensitive group-TS) (80.0 vs. 41.9 %, respectively, P = 0.009). Carriers of the ESR12014A mutant allele were more prevalent among the TR patients compared to the TS patients (26.3 vs. 8.0 %, respectively, P = 0.009). EGFR expression and the distribution pattern of ERα expression were associated with the response to tamoxifen by both univariate and multivariate logistic regression analyses. The presence of these markers either alone or in combination was correlated with the worse PFS for all patients. Analysis of the distribution pattern of ERα expression and the EGFR status in tumor tissue may be valuable for patient selection for tamoxifen adjuvant therapy.

Predictors of postoperative hemoglobin drop after laparoscopic myomectomy.

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Watrowski, Rafał; Jäger, Christoph; Forster, Johannes

2017-01-01

Laparoscopic myomectomy (LM) can be associated with significant bleeding. To identify factors influencing the postoperative hemoglobin (Hb) drop after LM. This is a retrospective, single-center study. We evaluated data of 150 consecutive patients undergoing LM due to intramural myomas between 2010 and 2015. The median age of the patients was 37 (23-53) years. The mean diameter of the largest myoma was 5.7 ±2.3 (1.5-12) cm. The mean surgical time was 83 ±38 (35-299) min. The median number of sutures was 3 (1-11). The mean postoperative Hb drop was 1.6 ±1.2 (0-6) g/dl, and the mean estimated blood loss was 261 ±159 (50-1700) ml. In the univariate analysis, the postoperative Hb drop correlated with the duration of surgery (p < 0.001), diameter of the largest myoma (p < 0.001), cumulative myoma weight (p < 0.001), and number of sutures (p < 0.001), but not with patients' age or number of intramural myomas. In the multivariable analysis, the surgical time ( β = 0.395, p < 0.001), diameter of the largest myoma ( β = 0.292, p = 0.03) and preoperative Hb concentration ( β = 0.299, p < 0.001) predicted the postoperative Hb change. Surgical time and dominant myoma diameter are independent predictors of the postoperative Hb drop after LM.

The efficacy of postoperative radiotherapy in localized primary soft tissue sarcoma treated with conservative surgery

International Nuclear Information System (INIS)

Zhao, Ru-Ping; Yu, Xiao-Li; Zhang, Zhen; Jia, Li-Juan; Feng, Yan; Yang, Zhao-Zhi; Chen, Xing-Xing; Wang, Jian; Ma, Sheng-Lin; Guo, Xiao-Mao

2016-01-01

To evaluate the efficacy of postoperative radiotherapy (RT) on local failure-free survival (LFFS), distant metastasis-free survival (DMFS) and overall survival (OS) in patients with localized primary soft tissue sarcoma (STS) and to identify prognostic factors. Between January 2000 and July 2010, 220 consecutive patients with localized primary STS, who received conservative surgery with or without postoperative RT, were enrolled in the study. Survival curves were constructed by the Kaplan-Meier method and log-rank test was used to assess statistical significance. Multivariate analysis was applied to identify the prognostic factors. After a median follow-up of 68 months (range, 5–127 months), the 5-year LFFS, DMFS and OS were 70.0, 78.2 and 71.2 %, respectively. Tumor size, histological subtypes, margin status and postoperative RT were independent predictors for OS. Postoperative RT was associated with a significant reduced local recurrence risk versus surgery alone (hazard ratio [HR] = 0.408, 95 % confidence interval [CI] 0.235–0.707, P = 0.001), with 5-year LFFS of 81.1 and 63.6 %, respectively (log-rank, P = 0.004). The log-rank test showed that postoperative RT had a tendency of improving OS compared with surgery alone, with 5-year OS of 74.8 and 65.0 %, respectively (P = 0.089). Multivariate analysis demonstrated that postoperative RT significantly reduced mortality rate compared with surgery alone (HR = 0.512, 95 % CI 0.296–0.886, p = 0.017), especially in patients with liposarcoma (p = 0.034). Postoperative radiotherapy reduce both local recurrence and STS mortality in patients with localized primary STS. The efficacy of RT on survival warrants further prospective study. The online version of this article (doi:10.1186/s13014-016-0605-y) contains supplementary material, which is available to authorized users

Phenotype anchoring in zebrafish reveals a potential role for matrix metalloproteinases (MMPs) in tamoxifen's effects on skin epithelium

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Bugel, Sean M., E-mail: Sean.Bugel@oregonstate.edu; Wehmas, Leah C., E-mail: wehmasl@onid.oregonstate.edu; La Du, Jane K., E-mail: Jane.LaDu@oregonstate.edu; Tanguay, Robert L., E-mail: Robert.Tanguay@oregonstate.edu

2016-04-01

The zebrafish is a powerful alternative model used to link phenotypes with molecular effects to discover drug mode of action. Using a zebrafish embryo-larval toxicity bioassay, we evaluated the effects of tamoxifen — a widely used anti-estrogen chemotherapeutic. Zebrafish exposed to ≥ 10 μM tamoxifen exhibited a unique necrotic caudal fin phenotype that was rapidly induced regardless of developmental life-stage when treatment was applied. To define tamoxifen's bioactivity resulting in this phenotype, targeted gene expression was used to evaluate 100 transcripts involved in tissue remodeling, calcium signaling, cell cycle and cell death, growth factors, angiogenesis and hypoxia. The most robustly misregulated transcripts in the tail were matrix metalloproteinases mmp9 and mmp13a, induced 127 and 1145 fold, respectively. Expression of c-fos, c-jun, and ap1s1 were also moderately elevated (3–7 fold), consistent with AP-1 activity — a transcription factor that regulates MMP expression. Immunohistochemistry confirmed high levels of induction for MMP13a in affected caudal fin skin epithelial tissue. The necrotic caudal fin phenotype was significantly attenuated or prevented by three functionally unique MMP inhibitors: EDTA (metal chelator), GM 6001 (broad MMP inhibitor), and SR 11302 (AP-1 transcription factor inhibitor), suggesting MMP-dependence. SR 11302 also inhibited induction of mmp9, mmp13a, and a putative MMP target, igfbp1a. Overall, our studies suggest that tamoxifen's effect is the result of perturbation of the MMP system in the skin leading to ectopic expression, cytotoxicity, and the necrotic caudal fin phenotype. These studies help advance our understanding of tamoxifen's non-classical mode of action and implicate a possible role for MMPs in tissues such as skin. - Highlights: • Tamoxifen rapidly induced a unique necrotic caudal fin phenotype in zebrafish. • Apoptosis co-localized temporally and spatially in the necrotic tail. �

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

Science.gov (United States)

Lee, Hyung-Sik; Choi, Youngmin; Hur, Won-Joo; Kim, Hyo-Jin; Kwon, Hyuk-Chan; Kim, Sung-Hyun; Kim, Jae-Seok; Lee, Jong-Hoon; Jung, Ghap-Joong; Kim, Min-Chan

2006-01-01

AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival. PMID:16489675

The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

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Danilo Ciccone Miguel

2010-11-01

Full Text Available The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.

Evaluation of post-operative prophylactic irradiation for carcinoma of the esophagus

International Nuclear Information System (INIS)

Mafune, Ken-ichi; Tanaka, Yoichi; Fujita, Kichishiro; Sakura, Mizuyoshi

1987-01-01

Of 147 patients with carcinoma of the esophagus resected at Saitama Cancer Center Hospital for 10 years, 98 cases were studied to evaluate post-operative prophylactic irradiation. The total dose of irradiation was up to 4,000 ∼ 5,000 rads of Linac X-ray and the irradiated field was T-shaped covering the upper mediastinal and bilateral cervical regions. The prognosis of the post-operative irradiated group (56 cases) was significantly better than that of the control group (42 cases) (p < 0.01). This study resulted in a five-year survival rate of 34.2 percent for patients in the post-operative irradiated group, compared to 16.7 percent for those in the control group. Further detailed comparative studies revealed similar results. Cancer recurrence occurred at the irradiated fields in 8 cases (14.3 %), though in 15 cases (35.7 %) of the control group. This suggested the local suppressive effect of the post-operative irradiation to the cancer recurrence. (author)

Are patient-reported outcomes predictive of patient satisfaction 5 years after anterior cervical spine surgery?

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Schroeder, Gregory D; Coric, Dom; Kim, Han Jo; Albert, Todd J; Radcliff, Kris E

2017-07-01

Patient satisfaction is becoming an increasing common proxy for surgical quality; however, the correlation between patient satisfaction and surgical outcomes 2 and 5 years after anterior cervical surgery has not been evaluated. The study aimed to determine if patient satisfaction is predicted by improvement in patient-reported outcomes (PRO) 2 and 5 years after anterior cervical spine surgery. This is a retrospective analysis of prospectively collected data. The sample included patients enrolled in the Food and Drug Administration investigational device exemption clinical trial comparing total disc replacement with Mobi-C cervical artificial disc and anterior cervical discectomy and fusion. The outcome measures were visual analog scale (VAS) neck pain score, Neck Disability Index (NDI), and Short-Form 12-Item scores, as well as patient satisfaction. Receiver operating characteristic curves were used to determine if improvement in different PRO metrics can accurately identify patient satisfaction. Additionally, a logistic regression analysis was performed on the results at 24 months and 60 months to identify independent predictors of patient satisfaction. This research was supported by LDR (Zimmer Biomet) 13785 Research Boulevard - Suite 200 Austin, TX 78750. Data were available for 512 patients at 60 months. At 24 months postoperatively, NDI score improvement (area under the curve [AUC]=0.806), absolute NDI score (AUC=0.823), and absolute VAS neck pain score (AUC=0.808) were all excellent predictors of patient satisfaction. At 60 months postoperatively, NDI score improvement (AUC=0.815), absolute NDI score (AUC=0.839), VAS neck pain score improvement (AUC=0.803), and absolute VAS neck pain score (AUC=0.861) were all excellent predictors of patient satisfaction. In patients undergoing one- and two-level anterior cervical spine surgery, between 2 and 5 years postoperatively, patient satisfaction is significantly predicted by PROs, including the VAS neck score and the

Effect of tamoxifen on fatty degeneration and atrophy of rotator cuff muscles in chronic rotator cuff tear: An animal model study.

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Cho, Edward; Zhang, Yue; Pruznak, Anne; Kim, H Mike

2015-12-01

Fatty degeneration of the rotator cuff muscles is an irreversible change resulting from chronic rotator cuff tear and is associated with poor clinical outcomes following rotator cuff repair. We evaluated the effect of Tamoxifen, a competitive estrogen receptor inhibitor, on fatty degeneration using a mouse model for chronic rotator cuff tear. Sixteen adult mice were divided into two diet groups (Tamoxifen vs. Regular) and subjected to surgical creation of a large rotator cuff tear and suprascapular nerve transection in their left shoulder with the right shoulder serving as a control. The rotator cuff muscles were harvested at 16 weeks and subjected to histology and RT-PCR for adipogenic and myogenic markers. Histology showed substantially decreased atrophy and endomysial inflammation in Tamoxifen group, but no significant differences in the amount of intramuscular adipocytes and lipid droplets compared to the Regular group. With RT-PCR, the operated shoulders showed significant upregulation of myogenin and PPAR-γ, and downregulation of myostatin compared to the nonsurgical shoulder. No significant differences of gene expression were found between the two diet groups. Our study demonstrated that tamoxifen diet leads to decreased muscle atrophy and inflammatory changes following chronic rotator cuff tear, but has no apparent effect on adipogenesis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Radiation recall dermatitis induced by Amol during tamoxifen therapy - case report

International Nuclear Information System (INIS)

Obtulowicz, A.; Pirowska, M.; Kosiniak-Kamysz, A.

2011-01-01

In the course of radiation therapy different types of adverse reactions of the skin are observed in approximately 95% of patients. Among the various complications encountered after radiotherapy, radiation recall dermatitis (RRD) deserves special attention. Radiation dermatitis is a form of delayed hypersensitivity of irradiated skin, and the direct trigger factors are medicines - most chemotherapeutics. The reaction is an inflammatory dermatosis. It is limited to previously irradiated skin and appears a number of months after radiotherapy. The aetiology of RRD is still unclear. Its clinical presentation may vary from mild erythema to necrosis and ulceration. The article presents the case of a 50-year-old patient, who after radiotherapy for breast cancer, during the hormonal therapy (tamoxifen), developed RRD type skin reactions after skin application of Amol. The article presents a detailed differential diagnosis of skin changes of RRD type, and discusses the principles of treatment and prevention. (authors)

Postoperative hemoglobin level in patients with femoral neck fracture.

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Nagra, Navraj S; Van Popta, Dmitri; Whiteside, Sigrid; Holt, Edward M

2016-01-01

The aim of this study was to analyze the changes of hemoglobin levels in patients undergoing fixation for femoral neck fracture. Peroperative hemoglobin levels of patients who underwent either dynamic hip screw (DHS) fixation (n=74; mean age: 80 years) or hip hemiarthroplasty (n=104; mean age: 84 years) for femoral neck fracture was monitored. There was a statistically and clinically significant mean drop of 31.1 g/L between the preoperative (D0) and postoperative Day 5 Hb levels (pmeasurement, DHS patients had lower hemoglobin values over hemiarthroplasty patients (p=0.046). The decrease in hemoglobin in the first 24-hour postoperative period (D0 to Day 1) is an underestimation of the ultimate lowest value in hemoglobin found at Day 2. Relying on the Day 1 hemoglobin level could be detrimental to patient care. We propose a method of predicting patients likely to be transfused and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring.

Intraoperative Tumor Perforation is Associated with Decreased 5-Year Survival in Colon Cancer

DEFF Research Database (Denmark)

Bundgaard, N S; Bendtsen, V O; Ingeholm, P

2017-01-01

BACKGROUND: It is a widely held belief that intraoperative tumor perforation in colon cancer impairs survival and causes local recurrence, although the prognostic importance remains unclear. AIM: The aim of this study was to assess the effect of unintended intraoperative tumor perforation...... on postoperative mortality and long-term survival. MATERIAL AND METHODS: This national cohort study was based on data from a prospectively maintained nationwide colorectal cancer database. We included 16,517 colon cancer patients who were resected with curative intent from 2001 to 2012. RESULTS: Intraoperative...... tumor perforation produced a significantly impaired 5-year survival of 40% compared to 64% in non-perforated colon cancer. Intraoperative tumor perforation was an independent risk factor for death, hazard ratio 1.63 (95% confidence interval: 1.4-1.94), with a significantly increased 90-day postoperative...

POSTOPERATIVE INFECTIOUS COMPLICATIONS IN PATIENTS WITH URINARY DISEASE

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A. Ch. Usupbaev

2018-01-01

Full Text Available The large proportion of postoperative infectious complications in urological hospitals makes extremely urgent the problem of its control. The high level of these complications in the postoperative period in patients with urolithiasis is caused by various endo- and exogenous factors.Purpose. To determine the frequency, structure, and features of postoperative infectious complications in patients with urolithiasis in urological hospitals.Materials and methods. As an object of research we used a medical card 232 of the operated patients with urolithiasis, which were copied out in individual registration card. Of 232 patients with urolithiasis 48.3% were men, their average age was 44.5 ± 9.4 years. Female patients were slightly larger (51.7%, respectively, the average age was 44.9 ± 8.1 years.Results. The most common postoperative infectious complications in urolithiasis was infection in the area of surgical intervention (36,2%, acute urethritis (20,7%, acute pyelonephritis (14.7 per cent, paranephritis (9,5%, acute orhoepididimit (7,8%, acute cystitis (6%, pionephrosis (3,4%, urosepsis (1.7 percent. In the etiological structure of infectious agents associated with medical care with the highest frequency, microorganisms of genera Escherichia coli (43%, Proteus (9.5%, Staphilococcus spp were isolated. (8.3% and Staphilococcus aureus (8.3%, and in 11.9% of cases, the Association of microorganisms. Analysis of the etiological structure of genera of the family Enterobacteriaceae resistant to β-lactam antibiotics showed that 63.2% of the amount to the genus strain of E. coli, 21% Proteus and 15.8% Klebsiella.Conclusion. The data obtained indicate the need for research on the prevalence of resistant strains of microorganisms, the introduction of more specifi c, sensitive methods and monitoring. This will increase the effectiveness of treatment, reduce the risk of the spread of resistant strains and increase nosocomial infections.

HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells

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Wen-Tsung Huang

2017-12-01

Full Text Available Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+ breast cancer patients. Even though dysregulations of histone deacetylases (HDACs are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan–Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.

25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.

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Amir, Eitan; Cecchini, Reena S; Ganz, Patricia A; Costantino, Joseph P; Beddows, Samantha; Hood, Nicola; Goodwin, Pamela J

2012-06-01

Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit.

A case of angiosarcoma that developed 10 years after postoperative radiotherapy for tongue cancer

International Nuclear Information System (INIS)

Sagae, Hitomi; Watanabe, Yoshihiro; Ozawa, Hiroyuki; Ogawa, Kaoru

2017-01-01

Angiosarcoma is a rare disease that accounts for about 1%-2% of all soft-tissue sarcomas and is a highly malignant tumor with a poor prognosis. Albeit not very common, in some cases, angiosarcomas can be induced by irradiation. In this study, we report the case of a patient who developed angiosarcoma at the site of previous postoperative radiotherapy for tongue cancer. The patient was a 63-year-old woman who had undergone surgery for tongue cancer (T4aN2cM0) and received irradiation (50 Gy in total) to the cervical region. The postoperative course had been uneventful, without recurrence. However, 10 years after the surgery, she began to develop a dark-red tumor in the right lower jaw, which was diagnosed as angiosarcoma by biopsy. Because imaging revealed evidence of neither lymph node metastasis nor distant metastasis, tumorectomy with reconstructive surgery using a pectoralis major myocutaneous flap was performed. She then received postoperative adjuvant chemotherapy. Thereafter, she has had an uneventful course, without any evidence of recurrence until date. This case serves to underscore the fact that exposure to radiation can result in new malignant tumor formation. Therefore, such patients need to be explained about the possibility of development of radiation-induced tumor and about the need for long-term follow-up after radiotherapy; they should also receive instructions to visit a medical facility in case they notice any abnormality at the site of previous irradiation. In the event a patient develops any abnormality, such as redness and/or swelling, at the site of previous irradiation, he/she a patient should immediately be worked up under the assumption of not only recurrence of the primary disease, but also possible radiation-induced tumor. The diagnosis must be established by methods such as biopsy. (author)

Ribavirin restores ESR1 gene expression and tamoxifen sensitivity in ESR1 negative breast cancer cell lines

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Sappok Anne

2011-12-01

Full Text Available Abstract Tumor growth is estrogen independent in approximately one-third of all breast cancers, which makes these patients unresponsive to hormonal treatment. This unresponsiveness to hormonal treatment may be explained through the absence of the estrogen receptor alpha (ESR1. The ESR1 gene re-expression through epigenetic modulators such as DNA methyltransferase inhibitors and/or histone deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast cancer cell lines and opens new treatment horizons in patients who were previously associated with a poor prognosis. In the study presented herein, we tested the ability of ribavirin, which shares some structural similarities with the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re-expression in ESR1 negative breast cancer cell lines. In our study we identified ribavirin to restore ESR1 gene re-expression alone and even more in combination with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction. Ribavirin and analogs could pave the way to novel translational research projects that aim to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based endocrine treatment strategies.

Postoperative radiation therapy for grade II and III intracranial ependymoma

International Nuclear Information System (INIS)

Mansur, David B.; Perry, Arie; Rajaram, Veena; Michalski, Jeff M.; Park, T.S.; Leonard, Jeffrey R.; Luchtman-Jones, Lori; Rich, Keith M.; Grigsby, Perry W.; Lockett, Mary Ann; Wahab, Sasha H.; Simpson, Joseph

2005-01-01

Purpose: To retrospectively determine the long-term outcome of intracranial ependymoma patients treated with surgery and postoperative radiation therapy. Methods and materials: Sixty patients were treated at our institution between 1964 and 2000. Forty patients had World Health Organization Grade II ependymoma, and 20 patients had Grade III ependymoma. The median patient age was 10.7 years. The majority of patients were male (55%), had infratentorial tumors (80%), and had subtotal resections (72%). Postoperative radiation therapy was delivered to all patients to a median total dose of 50.4 Gy. Craniospinal radiation therapy was used in the earlier era in only 12 patients (20%). Results: The median follow-up of surviving patients was 12.5 years. The 5-year and 10-year disease-free survival rates for all patients were 58.4% and 49.5%, respectively. The 5-year and 10-year overall survival rates for all patients were 71.2% and 55.0%, respectively. Supratentorial tumor location was independently associated with a worse disease-free survival. Subtotal resection and supratentorial location predicted a worse overall survival, but this failed to reach statistical significance. No statistically significant effect on prognosis was observed with tumor grade, patient age, or radiation dose or volume. Conclusion: Our long-term follow-up indicates that half of ependymoma patients will have disease recurrences, indicating the need for more effective treatments

The Possible Therapeutic Role of Polyphenyl Constituents in Turmeric and Tamoxifen on Hepatocellular Carcinoma Chemically Induced in Rats

International Nuclear Information System (INIS)

Abdelgawad, M.R.

2017-01-01

Tamoxifen is a drug wildly used for the adjuvant therapy in the treatment of women with estrogen receptor-positive breast tumors and has a low incidence of serious side-effects. Feeding turmeric ( Curcuma longa L .) to rats has no apparent side effects; reduced the types of inflammation that can cause liver cell damage, blockage and scarring. Turmeric delay the damage caused by progressive inflammatory liver disease. This study was carried out to study the possible therapeutic effect of polyphenyl constituents in turmeric and tamoxifen on hepatocarcinogenesis in rats chemically induced by diethylnitrosamine (DEN). Thirty five male rats were injected with DEN in a single dose i.p. (200mg/kg), 7 rats were sacrificed after ~6 months for histopathological examination for HCC nodules in different lobes and lobules, many nodules were observed by naked eye with a diameter of about ~2-3mm. The remaining 28 hepatoma (HCC) bearing rats chemically induced were randomized divided into 4 groups (each of 7rats): hepatoma bearing rats receiving the control diet; hepatoma bearing rats (supplemented with 4g/kg (wt/wt) turmeric (~200 μg curcumin /rat/day/4weeks; hepatoma bearing rats treated with 50mg/kg (wt/wt) tamoxifen dissolved in 0.1 ml dimethylsulfoxide and diluted with normal saline and drinking water; hepatoma bearing rats treated with 50mg/kg (wt/wt) tamoxifen in 0.1 ml dimethylsulfoxide and diluted with normal saline and drinking water and supplemented with 4g/ kg (wt/wt) turmeric(~200 μg curcumin /rat/day/4weeks; besides, 7 male rats serves as control group. By the end of the experiment at 4 weeks, rats in each group were sacrificed for examination.

Direct and Systemic Administration of a CNS-Permeant Tamoxifen Analog Reduces Amphetamine-Induced Dopamine Release and Reinforcing Effects.

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Carpenter, Colleen; Zestos, Alexander G; Altshuler, Rachel; Sorenson, Roderick J; Guptaroy, Bipasha; Showalter, Hollis D; Kennedy, Robert T; Jutkiewicz, Emily; Gnegy, Margaret E

2017-09-01

Amphetamines (AMPHs) are globally abused. With no effective treatment for AMPH addiction to date, there is urgent need for the identification of druggable targets that mediate the reinforcing action of this stimulant class. AMPH-stimulated dopamine efflux is modulated by protein kinase C (PKC) activation. Inhibition of PKC reduces AMPH-stimulated dopamine efflux and locomotor activity. The only known CNS-permeant PKC inhibitor is the selective estrogen receptor modulator tamoxifen. In this study, we demonstrate that a tamoxifen analog, 6c, which more potently inhibits PKC than tamoxifen but lacks affinity for the estrogen receptor, reduces AMPH-stimulated increases in extracellular dopamine and reinforcement-related behavior. In rat striatal synaptosomes, 6c was almost fivefold more potent at inhibiting AMPH-stimulated dopamine efflux than [ 3 H]dopamine uptake through the dopamine transporter (DAT). The compound did not compete with [ 3 H]WIN 35,428 binding or affect surface DAT levels. Using microdialysis, direct accumbal administration of 1 μM 6c reduced dopamine overflow in freely moving rats. Using LC-MS, we demonstrate that 6c is CNS-permeant. Systemic treatment of rats with 6 mg/kg 6c either simultaneously or 18 h prior to systemic AMPH administration reduced both AMPH-stimulated dopamine overflow and AMPH-induced locomotor effects. Finally, 18 h pretreatment of rats with 6 mg/kg 6c s.c. reduces AMPH-self administration but not food self-administration. These results demonstrate the utility of tamoxifen analogs in reducing AMPH effects on dopamine and reinforcement-related behaviors and suggest a new avenue of development for therapeutics to reduce AMPH abuse.

Therapeutic Results of Radiotherapy in Rectal Carcinoma -Comparison of Sandwich Technique Radiotherapy with Postoperative Radiotherapy

International Nuclear Information System (INIS)

Huh, Gil Cha; Suh, Hyun Suk; Lee, Hyuk Sang; Kim, Re Hwe; Kim, Chul Soo; Kim, Hong Yong; Kim, Sung Rok

1996-01-01

Purpose : To evaluate the potential advantage for 'sandwich' technique radiotherapy compared to postoperative radiotherapy in respectable rectal cancer. Between January 1989 and May 1994, 60 patients with respectable rectal cancer were treated at Inje University Seoul and Sanggye Paik Hospital.Fifty one patients were available for analysis : 20 patients were treated with sandwich technique radiotherapy and 31 patients were treated with postoperative radiotherapy. In sandwich technique radiotherapy(RT), patients were treated with preoperative RT 1500 cGy/5fx followed by immediate curative resection. Patients staged as Astler-Coller B2, C were considered for postoperative RT with 2500-4500 cGy. In postoperative RT, total radiation dose of 4500-6120 cGy, 180 cGy daily at 4-6 weeks was delivered. Patients were followed for median period of 25 months. Results : The overall 5-year survival rates for sandwich technique RT group and postoperative RT group were 60% and 71%, respectively(p>0.05). The 5-year disease free survival rates for each group were 63%. There was no difference in local failure rate between two groups(11% versus 7%). Incidence of distant metastasis was 11%(2/20) in the sandwich technique RT group and 20%(6/31) in the postoperative RT group(p>0.05). The frequencies of acute and chronic complications were comparable in both groups. Conclusion : The sandwich technique radiotherapy group shows local recurrence and survival similar to those of postoperative RT alone group but reduced distant metastasis compared to postoperative RT group. But long term follow-up and large number of patients is needed to make an any firm conclusion regarding the value of this sandwich technique RT

The Relation between Nonverbal IQ and Postoperative CI Outcomes in Cochlear Implant Users: Preliminary Result

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Mina Park

2015-01-01

Full Text Available Objectives. This study assessed the correlation between performance intelligence and the postoperative cochlear implant (CI outcome in Korean-speaking children. In addition, the relationship between the performance intelligence subscales and the post-CI speech outcome was evaluated. Materials and Methods. Thirteen pediatric CI users (five males, eight females; median age at implantation 6.2 (range 1.3–14.2 years; median age at intelligence test 9.3 (range 5–16 years who were tested using the Korean Educational Development Institute-Wechsler Intelligence Scale for children were studied. The correlations between the intelligence scores and 1-2 years postoperative Categories of Auditory Performance (CAP scores and between subscales of performance and 1-2 years postoperative CAP scores were analyzed. Results. There was no correlation between the categories of verbal intelligence quotient (IQ and performance IQ for “mentally retarded” and “average,” respectively (Spearman’s rho = 0.42, P=0.15. There was a strong correlation between performance IQ and the postoperative CAP scale (Spearman’s rho = 0.8977, P=0.0008. “Picture arrangement” and “picture completion,” reflecting social cognition, were strongly correlated with the postoperative CAP scales. Conclusion. Performance intelligence, especially social cognition, was strongly related to the postoperative CI outcome of cochlear implant users. Therefore, auditory rehabilitation, including social rehabilitation, should maximize the postoperative CI outcomes.

A 2 to 6 year postoperative evaluation of tension-free vaginal tape (tvt: a questionnaire based study

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Marijan Lužnik

2006-12-01

Full Text Available Background: The purpose of this article is to show the long-term subjective cure rate of urinary incontinence in patients after the tension-free vaginal tape (TVT procedure and eventual correlation of some factors with this cure rate.Methods: From December 1999 to July 2004 we performed one hundred and fifty TVT procedures at our Department of Gynecology and Obstetrics. In April 2006, a 2 to 6 year postoperatively, 149 questionnaires were sent to our patients for self-estimation of the cure rate. The subjective evaluation of results of the operation was based on definition of the improvement of continence in percents, with 13 possibilities ranging from –20 % to 100 %. With tests of correlation we wish to establish eventual connection between the cure rate of urinary incontinence and the age of women at the time of operation and the number of postoperative years. Statistical significance of eventual influence of independent variables on cure rate was analyzed using nonparametric tests in Statistical Program Package for Social Sciences (SPSS.Results: Of 119 answers, in 40 cases (33.6 % patients confirmed that they are completely healthy, and 87 women (73.1 % confirmed at least 70 % cure rate. 100 answers confirmed that 87.6 % patients had benefited by TVT procedure even 2 to 6 years postoperatively. Correlation between the long-term cure rate and the patient’s age at time of operation had Pearson’s correlation coefficient r = –0.335 and was statistically significant (p = 0.01. Statistically significantly different success was still in the groups with regard to the previous hysterectomy (p = 0.005 and the previous surgical procedure for urinary incontinence (p = 0.001. There was no statistically significant difference between the cure rate and the number of postoperative years (p = 0.236.Conclusions: 150 TVT procedures were performed very safely as solo intervention or as connected with other repair of pelvic organ prolapse at our

Postoperative radiotherapy for low grade glioma of the brain

International Nuclear Information System (INIS)

Chun, Ha Chung; Lee, Myung Za

2000-01-01

To evaluate the effectiveness and tolerance of postoperative external beam radiotherapy for patients with low grade glioma of the brain and define the optimal radiotherapeutic regimen. Between June, 1985 and May, 1998, 72 patients with low grade gliomas were treated with postoperative radiotherapy immediately following surgery. Median age was 37 years with range of 11 to 76 years. Forty one patients were male and 31 patients were female with male to female ratio of 1.3:1. Of those patients, 15 underwent biopsy alone and remaining 57 did subtotal resection. The distribution of the patients according to histologic type was as follows: astrocytomas-42 patients (58%), mixed oligodendrogliomas-19 patients (27%), oligodendrogliomas-11 patients (15%). Two patients were treated with whole brain irradiation followed by cone down boost and remaining 70 patients were treated with localized field with appropriate margin. All of the patients were treated with conventional once a day fractionation. Most of patients received total tumor dose of 5000-5500 cGy. The overall 5 and 7 year survival rates for entire group of 72 patients were 61% and 50%. Corresponding disease free survival rates for entire patients were 53% and 45%, respectively. The 5 and 7 year overall survival rates for astrocytomas, mixed oligodendrogliomas, and oligodendrogliomas were 48% and 45%, 76% and 56%, and 80% and 52%, respectively. Patients who underwent subtotal resection showed better survival rates than those who did biopsy alone. The overall 5 year survival rates for subtotal resection patients and biopsy alone patients were 67% and 43%, respectively. Forty six patients who were 40 years or younger survived better than 26 patients who were 41 years or older (overall survival rate at 5 years, 69% vs 45%). Although one patient was not able to complete the treatment because of neurological deterioration, there was no significant treatment related acute toxicities. Postoperative radiotherapy was safe and

The Incidence of Postoperative Pneumonia in Various Surgical Subspecialties: A Dual Database Analysis.

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Chughtai, Morad; Gwam, Chukwuweike U; Khlopas, Anton; Newman, Jared M; Curtis, Gannon L; Torres, Pedro A; Khan, Rafay; Mont, Michael A

2017-07-25

Pneumonia is the third most common postoperative complication. However, its epidemiology varies widely and is often difficult to assess. For a better understanding, we utilized two national databases to determine the incidence of postoperative pneumonia after various surgical procedures. Specifically, we used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and the Nationwide Inpatient Sample (NIS) to determine the incidence and yearly trends of postoperative pneumonia following orthopaedic, urologic, otorhinolaryngologic, cardiothoracic, neurosurgery, and general surgeries. The NIS and NSQIP databases from 2009-2013 were utilized. The Clinical Classification Software (CCS) for International Classification of Diseases, 9th edition (ICD-9) codes provided by the NIS database was used to identify all surgical subspecialty procedures. The incidence of postoperative pneumonia was identified as the total number of cases under each identifying CCS code that also had ICD-9 codes for postoperative pneumonia. In the NSQIP database, the surgical subspecialties were selected using the following identifying string variables provided by NSQIP: 1) "Orthopedics", 2) "Otolaryngology (ENT)", 3) "Urology", 4) "Neurosurgery", 5) "General Surgery", and 6) "Cardiac Surgery" and "Thoracic Surgery". Cardiac and thoracic surgery was merged to create the variable "Cardiothoracic Surgery". Postoperative pneumonia cases were extracted utilizing the available NSQIP nominal variables. All variables were used to isolate the incidences of postoperative pneumonia stratified by surgical specialty. A subsequent trend analysis was conducted to assess the associations between operative year and incidence of postoperative pneumonia. For all NIS surgeries, the incidence of postoperative pneumonia was 0.97% between 2009 and 2013. The incidence was highest among patients who underwent cardiothoracic surgery (3.3%) and urologic surgery (1.73%). Patients who

Orthovoltage X-rays for Postoperative Treatment of Resected Basal Cell Carcinoma in the Head and Neck Area.

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Duinkerken, Charlotte W; Lohuis, Peter J F M; Crijns, Marianne B; Navran, Arash; Haas, Rick L M; Hamming-Vrieze, Olga; Klop, W Martin C; van den Brekel, Michiel W M; Al-Mamgani, Abrahim

Surgery is the golden standard for treating basal cell carcinomas. In case of positive tumor margins or recurrent disease, postoperative adjuvant or salvaging therapy is suggested to achieve good local control. To retrospectively report on local control and toxicity of postoperative radiotherapy by means of orthovoltage X-rays for residual or recurrent basal cell carcinoma after surgery in the head and neck area. Sixty-six surgically resected residual or recurrent basal cell carcinomas of the head and neck region were irradiated postoperatively by means of orthovoltage X-rays at the Netherlands Cancer Institute between January 2000 and February 2015. After a median follow-up duration of 30.5 months, only 5 recurrences were reported. The 5-year local control rates at 1, 3, and 5 years were 100%, 87%, and 87%, respectively. The 5-year local control rate was 92% for immediate postoperative radiotherapy of incompletely resected basal cell carcinomas, 90% for recurrences after 1 previously performed excision, and 71% for multiple recurrences, namely, a history of more than 1 excision ( P = .437). Acute toxicity healed spontaneously within 3 months. Late toxicities were mild. Radiotherapy by means of orthovoltage X-ray is an excellent alternative for re-excision in case of incompletely resected or recurrent basal cell carcinomas that are at risk of serious functional and cosmetic impairments after re-excision, with a 5-year local control rate of 87% and a low toxicity profile.

Urinary tract infections and post-operative fever in percutaneous nephrolithotomy.

Science.gov (United States)

Gutierrez, Jorge; Smith, Arthur; Geavlete, Petrisor; Shah, Hemendra; Kural, Ali Riza; de Sio, Marco; Amón Sesmero, José H; Hoznek, András; de la Rosette, Jean

2013-10-01

To review the incidence of UTIs, post-operative fever, and risk factors for post-operative fever in PCNL patients. Between 2007 and 2009, consecutive PCNL patients were enrolled from 96 centers participating in the PCNL Global Study. Only data from patients with pre-operative urine samples and who received antibiotic prophylaxis were included. Pre-operative bladder urine culture and post-operative fever (>38.5°C) were assessed. Relationship between various patient and operative factors and occurrence of post-operative fever was assessed using logistic regression analyses. Eight hundred and sixty-five (16.2%) patients had a positive urine culture; Escherichia coli was the most common micro-organism found in urine of the 350 patients (6.5%). Of the patients with negative pre-operative urine cultures, 8.8% developed a fever post-PCNL, in contrast to 18.2% of patients with positive urine cultures. Fever developed more often among the patients whose urine cultures consisted of Gram-negative micro-organisms (19.4-23.8%) versus those with Gram-positive micro-organisms (9.7-14.5%). Multivariate analysis indicated that a positive urine culture (odds ratio [OR] = 2.12, CI [1.69-2.65]), staghorn calculus (OR = 1.59, CI [1.28-1.96]), pre-operative nephrostomy (OR = 1.61, CI [1.19-2.17]), lower patient age (OR for each year of 0.99, CI [0.99-1.00]), and diabetes (OR = 1.38, CI [1.05-1.81]) all increased the risk of post-operative fever. Limitations include the use of fever as a predictor of systemic infection. Approximately 10% of PCNL-treated patients developed fever in the post-operative period despite receiving antibiotic prophylaxis. Risk of post-operative fever increased in the presence of a positive urine bacterial culture, diabetes, staghorn calculi, and a pre-operative nephrostomy.

A Prospective Study of Postoperative Vomiting in Children Undergoing Different Surgical Procedures under General Anaesthesia

Directory of Open Access Journals (Sweden)

Jaya Choudhary

2008-01-01

Full Text Available To identify the risk factors associated with postoperative vomiting (POV in paediatric population undergoing common surgeries. The risk factors studied for association with POV were age> 5 years, female gender, previous history of POV/motion sickness, type of surgery and duration of anaesthesia> 45 min. A total of 100 ASA grade I and II patients of either sex aged between 2-12 years undergoing elective surgical procedures were screened for the study. All patients underwent similar anaesthe-sia protocol and received two antiemetic agents (ondansetron 0.05mg.kg-1 and dexamethasone 0.15mg.kg-1 in premedication. The patients were observed for 24 hours postoperatively for the incidence of vomiting, number of times rescue antiemetic given and any adverse reaction to antiemetic.Overall 34% patients (34/100 developed POV of which 26 had only one episode and 8 patients had 2 episodes during first 24 h. Incidence of POV was 13% (13/100 in first 4 h whereas it was 29% (29/100 in late postoperative period. In early post operative period, POV was not associated significantly with any predicted risk factors. However, age>5years, duration of anaesthesia>45 minutes and history of motion sickness/POV were significantly associated in late postoperative period(4-24h. Female gender and type of surgery were not associated with increased POV. The combination antiemetic effectively prevented POV in early postoperative period (0-4h only but not in late postoperative period(0-24h.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

Science.gov (United States)

Dominick, Sally; Hickey, Martha; Chin, Jason; Su, H Irene

2015-12-09

Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or

Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

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Newman, M F; Grocott, H P; Mathew, J P; White, W D; Landolfo, K; Reves, J G; Laskowitz, D T; Mark, D B; Blumenthal, J A

2001-12-01

The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

Postoperative Radiation Therapy in Resected N2 Stage Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lee, Chang Geol

1993-01-01

A total of forty patients with resected N2 stage non-small cell lung cancer treated with postoperative adjuvant radiation therapy between Jan. 1975 and Dec. 1990 at the Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei Cancer Center were retrospectively analysed to evaluate whether postoperative radiation therapy improves survival. Patterns of failure and prognostic factors affecting survival were also analysed. The 5 year overall and disease free survival rate were 26.3%, 27.3% and median survival 23.5 months. The 5 year survival rates by T-stage were T1 66.7%, T2 25.6% and T3 12.5%. Loco-regional failure rate was 14.3% and distant metastasis rate was 42.9% and both 2.9%. Statistically significant factor affecting distant failure rate was number of positive lymph nodes(>= 4). This retrospective study suggests that postoperative radiation therapy in resected N2 stage non-small cell lung cancer can reduce loco-regional recurrence and may improve survival rate as compared with other studies which were treated by surgery alone. Further study of systemic control is also needed due to high rate of distant metastasis

Postoperative Pain in Children After Dentistry Under General Anesthesia.

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Wong, Michelle; Copp, Peter E; Haas, Daniel A

2015-01-01

The objective of this study was to determine the prevalence, severity, and duration of postoperative pain in children undergoing general anesthesia for dentistry. This prospective cross-sectional study included 33 American Society of Anesthesiology (ASA) Class I and II children 4-6 years old requiring multiple dental procedures, including at least 1 extraction, and/or pulpectomy, and/or pulpotomy of the primary dentition. Exclusion criteria were children who were developmentally delayed, cognitively impaired, born prematurely, taking psychotropic medications, or recorded baseline pain or analgesic use. The primary outcome of pain was measured by parents using the validated Faces Pain Scale-Revised (FPS-R) and Parents' Postoperative Pain Measure (PPPM) during the first 72 hours at home. The results showed that moderate-to-severe postoperative pain, defined as FPS-R ≥ 6, was reported in 48.5% of children. The prevalence of moderate-to-severe pain was 29.0% by FPS-R and 40.0% by PPPM at 2 hours after discharge. Pain subsided over 3 days. Postoperative pain scores increased significantly from baseline (P children do experience moderate-to-severe pain postoperatively. Although parents successfully used pain scales, they infrequently administered analgesics.

17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

Science.gov (United States)

Catanuto, Paola; Doublier, Sophie; Lupia, Enrico; Fornoni, Alessia; Berho, Mariana; Karl, Michael; Striker, Gary E; Xia, Xiaomei; Elliot, Sharon

2009-06-01

Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated db/db mice, a model of type 2 diabetic glomerulosclerosis, with 17beta-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17beta-estradiol treatment decreased podocyte transforming growth factor-beta mRNA expression but increased that of the estrogen receptor subtype beta protein. 17beta-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17beta-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.

Postoperative weight bearing and patient reported outcomes at one year following tibial plateau fractures.

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Thewlis, Dominic; Fraysse, Francois; Callary, Stuart A; Verghese, Viju Daniel; Jones, Claire F; Findlay, David M; Atkins, Gerald J; Rickman, Mark; Solomon, Lucian B

2017-07-01

Tibial plateau fractures are complex and the current evidence for postoperative rehabilitation is weak, especially related to the recommended postoperative weight bearing. The primary aim of this study was to investigate if loading in the first 12 weeks of recovery is associated with patient reported outcome measures at 26 and 52 weeks postoperative. We hypothesized that there would be no association between loading and patient reported outcome measures. Seventeen patients, with a minimum of 52-week follow-up following fragment-specific open reduction and internal fixation for tibial plateau fracture, were selected for this retrospective analysis. Postoperatively, patients were advised to load their limb to a maximum of 20kg during the first 6 weeks. Loading data were collected during walking using force platforms. A ratio of limb loading (affected to unaffected) was calculated at 2, 6 and 12 weeks postoperative. Knee Injury and Osteoarthritis Scores were collected at 6, 12, 26 and 52 weeks postoperative. The association between loading ratios and patient reported outcomes were investigated. Compliance with weight bearing recommendations and changes in the patient reported outcome measures are described. Fracture reduction and migration were assessed on plain radiographs. No fractures demonstrated any measurable postoperative migration at 52 weeks. Significant improvements were seen in all patient reported outcome measures over the first 52 weeks, despite poor adherence to postoperative weight bearing restrictions. There were no associations between weight bearing ratio and patient reported outcomes at 52 weeks postoperative. Significant associations were identified between the loading ratio at 2 weeks and knee-related quality of life at six months (R 2 =0.392), and between the loading ratio at 6 weeks combined with injury severity and knee-related quality of life at 26 weeks (R 2 =0.441). In summary, weight bearing as tolerated does not negatively affect the

Postoperative enhancement on breast MRI: Time course and pattern of changes.

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Mahoney, Mary C; Sharda, Radhika G

2018-04-23

Expected postoperative enhancement on breast MRI can appear similar to enhancement seen in recurrent or residual malignancy. Our aim was to assess the time course and patterns of enhancement at the surgical site, thereby helping to distinguish between benign and malignant postoperative enhancement. In 200 MRI scans performed in 153 patients after breast conservation treatment, 43 after surgical excision of atypia, and 4 patients after benign excisional biopsy were categorized by postoperative time interval. We defined 4 patterns of morphologic enhancement on MRI: cavity wall/seroma (Pattern I); thin linear (Pattern II); mass (Pattern III); and fat necrosis (Pattern IV). Of 200 MRI scans, 66 (33%) demonstrated enhancement at the surgical site. Enhancement typically decreased through the postoperative follow-up period. Enhancement was observed in 41% (28/68) of cases beyond the 18-month interval but was uncommon after 5 years. Pattern III enhancement was the morphologic pattern seen most commonly with malignancy (5/19 cases, 26%). When associated with delayed washout kinetics, it was even more strongly predictive of malignancy (4/5 cases, 80%). In patients with a history of excisional biopsy and no prior radiation treatment, the percentage of MRI scans showing enhancement was significantly lower than (21% vs 49% with P-value .0027) in patients who had undergone radiation. Enhancement at the surgical site occurred in one-third of cases up to 5 years after surgery, particularly in patients who underwent both radiation and surgery. Mass enhancement, particularly in conjunction with delayed washout kinetics, is most predictive of malignancy and should prompt biopsy or re-excision. © 2018 Wiley Periodicals, Inc.

[Effect of Evn-50 on cell growth and apoptosis in tamoxifen-resistance human breast cancer cell line MCF-7/TAM-R].

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Hu, Hui-yong; Zhou, Jun; Wan, Fang; Dong, Li-feng; Zhang, Feng; Wang, Yi-ke; Chen, Fang-fang; Chen, Yi-ding

2012-09-01

To investigate the effect of Evn-50 extracted from Vitex negundo on human breast cancer cell line MCF-7 and MCF-7/TAM-R cells in vitro. MCF-7 and tamoxifen-resistant MCF-7/TAM-R cells were treated with Evn-50,tamoxifen or combination of Evn-50 and tamoxifen. Cell proliferation inhibition rates were determined by MTT assay. The apoptosis rate and the change of cell cycle were detected by PI staining flow cytometry. Protein expression of phospho-MAPK 44/42 (Thr202/Tyr204),MAPK P44/42, phospho-AKT (Ser473) and AKT were detected with Western blotting. The viability of MCF-7 cells was decreased in combination group [(28.65 ±11.43)%] and Evn-50 group [(53.02 ±15.14)%] compared with TAM group (PTAM-R in combination group [(42.11 ±14.30)%] was significantly lower than that in TAM group [(92.18 ±13.16)%] (PTAM-R cells,the expression of phosphorylation of AKT and MAPK44/42 protein was not changed in Evn-50 or TAM alone group,but significantly inhibited in the combination group at 72 h. Evn-50 can inhibit cell growth and induce apoptosis in MCF-7 and MCF-7/TAM-R cells,it can reverse tamoxifen-resistance of MCF-7/TAM-R cells.The mechanisms may be related to the down-regulation of phosphorylated ERK1/2 in MAPK signal pathway and phosphorylated AKT in AKT signal pathway.

Post-operative swallowing in multiple system atrophy.

Science.gov (United States)

Ueha, R; Nito, T; Sakamoto, T; Yamauchi, A; Tsunoda, K; Yamasoba, T

2016-02-01

Some patients with multiple system atrophy (MSA) require surgical interventions such as tracheostomy and aspiration prevention. Few studies have investigated the postoperative clinical course of MSA patients. The aim of this study was to determine a management strategy for dysphagia and respiratory disorder in MSA. From 2001 to 2014, 18 MSA patients (13 males and 5 females, 52-76 years) underwent tracheostomy (TR, n = 11) or laryngeal closure (LC, n = 12). Five patients underwent LC following TR. Vocal fold impairment, the degree of dysphagia and pre/post-operative oral ingestion, and postoperative survival time were evaluated retrospectively. Swallowing function was assessed using the penetration aspiration scale (PAS). TR was performed due to respiratory disorder in seven patients and due to dysphagia in four patients. PAS scores ranged 1-8 in TR patients and 7-8 in LC patients. Seven of 11 patients who underwent TR displayed worsened PAS scores, and no patients displayed improved PAS scores following TR. All patients who underwent LC regained complete or partial oral intake after surgery. There were no significant differences in postoperative survival time between the two groups. Considering the impacts of TR and LC on survival time, postoperative feeding and swallowing, LC is a good option for treating MSA patients with dysphagia. © 2015 EAN.

CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with adjuvant tamoxifen and its association with disease recurrence

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De Ameida Melo, Mariella; De Vasconcelos-Valença, Rodrigo José; Neto, Fidelis Manes; Borges, Rafael Soares; Costa-Silva, Danylo Rafhael; Da Conceição Barros-Oliveira, Maria; Borges, Umbelina Soares; Alencar, Airlane Pereira; Silva, Vladimir Costa; Da Silva, Benedito Borges

2016-01-01

At present, there is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms, in terms of recurrence and overall survival. Thus, the aim of the present study was to investigate the association of the CYP2D6 *4, *10 and *17 gene polymorphisms with breast cancer recurrence in a Brazilian population. The cohort comprised 40 receptor-positive breast cancer patients without recurrence and 40 with distant recurrence. A 3-ml sample of peripheral blood was collected from each patient to determine the presence of the *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by quantitative polymerase chain reaction analysis. There was no statistically significant difference between the two groups regarding the polymorphism frequency (P=0.246). The results revealed that intermediate metabolizers occurred in 5% of patients without recurrence and in 15% of those with distant recurrence. Poor metabolizers occurred in only 1 patient (2.5%) per group, and there was no significant difference between the groups (P=0.789). The present study concluded that the CYP2D6 gene polymorphism in women with hormone-sensitive breast cancer treated with tamoxifen was not associated with disease recurrence. PMID:27882219

Integrative analyses of gene expression and DNA methylation profiles in breast cancer cell line models of tamoxifen-resistance indicate a potential role of cells with stem-like properties

DEFF Research Database (Denmark)

Lin, Xue; Li, Jian; Yin, Guangliang

2013-01-01

Development of resistance to tamoxifen is an important clinical issue in the treatment of breast cancer. Tamoxifen resistance may be the result of acquisition of epigenetic regulation within breast cancer cells, such as DNA methylation, resulting in changed mRNA expression of genes pivotal for es...

A retrospective analysis of the postoperative use of loteprednol etabonate gel 0.5% following laser-assisted in situ keratomileusis or photorefractive keratectomy surgery.

Science.gov (United States)

Salinger, Clifford L; Gordon, Michael; Jackson, Mitchell A; Perl, Theodore; Donnenfeld, Eric

2015-01-01

While loteprednol etabonate ophthalmic gel 0.5% (LE gel) is approved for treatment of postoperative ocular inflammation and pain, there have been no reported studies in patients undergoing laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK). This was a retrospective chart review conducted at five refractive surgical centers in the USA. Data were collected from primary LASIK or PRK surgery cases in which LE gel was used postoperatively as the clinician's routine standard of care and in which patients were followed-up for up to 6 months. Data extracted from charts included patient demographics, surgical details, LE gel dosing regimen, pre- and postsurgical refractive characteristics, intraocular pressure (IOP) measurements, and visual acuity. Primary outcomes included postoperative IOP elevations, adverse events, and early discontinuations. Data were collected on 189 LASIK eyes (96 patients) and 209 PRK eyes (108 patients). Mean (standard deviation [SD]) years of age at surgery was 36.0 (11.7) and 33.9 (11.3) in LASIK and PRK patients. LE gel was prescribed most often four times daily during the first postoperative week, regardless of procedure; the most common treatment duration was 7-14 days in LASIK and ≥30 days in PRK patients. No unusual corneal findings or healing abnormalities were reported. Mean postoperative uncorrected distance visual acuity was 20/24 in LASIK and 20/30 in PRK eyes. Mild/trace corneal haze was reported in 20% of PRK patients; two PRK patients with moderate/severe corneal haze were switched to another corticosteroid. Mean postoperative IOP did not increase over time in either LASIK or PRK eyes (P≥0.331); clinically significant elevations from baseline in IOP (≥10 mmHg) were noted in only three eyes of two PRK patients. LE gel appears to have a high level of safety and tolerability when used for the management of postoperative pain and inflammation following LASIK and PRK surgery.

Cumulative incidence of postoperative severe pain at Hospital Universitario San Jose, Popayan. Preliminar report

Directory of Open Access Journals (Sweden)

Ingrid Muñoz

2013-12-01

Full Text Available Introduction: Postoperative pain remains as a problem. National studies report incidences of 31% for moderate and 22% for severe pain. Inadequate analgesia is related to dissatisfaction and adverse outcomes. The aim of this study was to describe the incidence and characteristics of the postoperative pain in the post-anesthesia care unit (PACU at Hospital Universitario San José of Popayán (HUSJ in patients undergoing general anesthesia during the first postoperative hour. Methods: Cohort study. We recruited patients attending PACU and undergoing procedures using general anesthesia, between 18 and 70 years. Using a standardized collection form medical history, demographic data, medical history, anesthetic management, intraoperative analgesia and postoperative pain assessment by verbal and numerical pain scale (1-10 were recorded. Postoperative outcome data were also collected in the PACU. Results: The incidence of severe postoperative pain at 10 minutes was 12.3% 95%CI [7.1-18.2] (19 patients. Within 30 minutes of assessment 4.5% 95%CI [1.3-8.4] (7 patients and 1.9% 60 minutes 95%CI [0-4.5] (3 patients. 48.7% required rescue analgesic at PACU. Incidence of postoperative nausea and vomiting (PONV was significantly different in patients requiring rescue analgesic. Conclusion: The incidence of severe postoperative pain in the first postoperative hour at HUSJ is close to 12% and it decreases as time goes by. Patients requiring rescue analgesic have a higher incidence of postoperative complications such as PONV.

Postoperative CPAP use impacts long-term weight loss following bariatric surgery.

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Collen, Jacob; Lettieri, Christopher J; Eliasson, Arn

2015-03-15

Obstructive sleep apnea (OSA) is common among bariatric surgery candidates. After surgical weight loss, OSA frequently persists and untreated OSA can lead to weight gain. Long-term continuous positive airway pressure (CPAP) adherence is unclear and poor adherence may worsen weight loss outcomes. We sought to determine the impact of CPAP use on long-term weight-loss outcomes in a cohort of bariatric patients. Long-term observational study of bariatric surgery patients with OSA. Patients were evaluated with polysomnography preoperatively and one-year postoperatively. The cohort was again evaluated a mean of 7.2 years later to determine the relationship between long-term CPAP use and subsequent regain of weight. Twenty-four consecutive patients (aged 48.5 ± 9.4 years at time of surgery; 73% female) were included in the initial assessment, and long-term outcome data were available on 22 subjects. Persistent OSA was documented in 21 of 22 subjects (95%) one year postoperatively. Final evaluation occurred 7.2 ± 2.3 years following surgery. Weight (213.3 ± 39.1 to 235.3 ± 47.1 lb, p = 0.10) and BMI (32.5 ± 5.4 to 37.3 ± 8.2 kg/m(2), p = 0.03) increased in most (n = 19, 86.4%) from postoperative to final evaluation. CPAP use declined from 83.3% (preoperatively) to 38.1% (one year) and to 23.8% (final evaluation). BMI increased among those not using CPAP at long-term follow-up compared to those with continued CPAP use (6.8% v -1.8%, p = 0.05). In our cohort of bariatric patients with OSA, long-term adherence to CPAP therapy was poor, and non-adherence was associated with weight gain. Ongoing follow-up of OSA in this population may help to preserve initial achievements after surgical weight loss. © 2014 American Academy of Sleep Medicine.

Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen

NARCIS (Netherlands)

Jager, N G L; Rosing, H; Schellens, J H M; Beijnen, J H; Linn, S C

The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)-endoxifen in serum has been proposed. The objective of this research was to establish the relationship between dried blood spot (DBS) and serum

Prognostic significance of postoperative pneumonia after curative resection for patients with gastric cancer.

Science.gov (United States)

Tu, Ru-Hong; Lin, Jian-Xian; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lu, Jun; Chen, Qi-Yue; Cao, Long-Long; Lin, Mi; Zheng, Chao-Hui; Huang, Chang-Ming

2017-12-01

Few studies have been designed to investigate the incidence of postoperative pneumonia after radical gastrectomy and its effect on prognosis of these patients. Incidences of postoperative pneumonia after radical gastrectomy in our department between January 1996 and December 2014 were summarized. Their effects on prognosis were retrospectively analyzed using survival curves and Cox regression. A total of 5237 patients were included in this study, 767 (14.4%) of them had complications, including 383 cases of postoperative pneumonia (7.2%). The 5-year overall and disease-specific survival of patients with postoperative pneumonia were both lower than those without this complication (P pneumonia were independent risk factors for disease-specific survival. Postoperative pneumonia after radical gastrectomy is an independent risk factor for prognosis of gastric cancer patients, especially in stage III. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

An analysis of postoperative thigh symptoms after minimally invasive transpsoas lumbar interbody fusion.

Science.gov (United States)

Cummock, Matthew D; Vanni, Steven; Levi, Allan D; Yu, Yong; Wang, Michael Y

2011-07-01

The minimally invasive transpsoas interbody fusion technique requires dissection through the psoas muscle, which contains the nerves of the lumbosacral plexus posteriorly and genitofemoral nerve anteriorly. Retraction of the psoas is becoming recognized as a cause of transient postoperative thigh pain, numbness, paresthesias, and weakness. However, few reports have described the nature of thigh symptoms after this procedure. The authors performed a review of patients who underwent the transpsoas technique for lumbar spondylotic disease, disc degeneration, and spondylolisthesis treated at a single academic medical center. A review of patient charts, including the use of detailed patient-driven pain diagrams performed at equal preoperative and follow-up intervals, investigated the survival of postoperative thigh pain, numbness, paresthesias, and weakness of the iliopsoas and quadriceps muscles in the follow-up period on the ipsilateral side of the surgical approach. Over a 3.2-year period, 59 patients underwent transpsoas interbody fusion surgery. Of these, 62.7% had thigh symptoms postoperatively. New thigh symptoms at first follow-up visit included the following: burning, aching, stabbing, or other pain (39.0%); numbness (42.4%); paresthesias (11.9%); and weakness (23.7%). At 3 months postoperatively, these percentages decreased to 15.5%, 24.1%, 5.6%, and 11.3%, respectively. Within the patient sample, 44% underwent a 1-level, 41% a 2-level, and 15% a 3-level transpsoas operation. While not statistically significant, thigh pain, numbness, and weakness were most prevalent after L4-5 transpsoas interbody fusion at the first postoperative follow-up. The number of lumbar levels that were surgically treated had no clear association with thigh symptoms but did correlate directly with surgical time, intraoperative blood loss, and length of hospital stay. Transpsoas interbody fusion is associated with high rates of immediate postoperative thigh symptoms. While larger

Basis for new strategies in postoperative radiotherapy of bronchogenic carcinoma

International Nuclear Information System (INIS)

Choi, N.C.H.; Grillo, H.C.; Gardiello, M.; Scannel, J.G.; Wilkins, E.W. Jr.

1980-01-01

In order to improve our understanding of the role of postoperative radiotherapy and to search for new strategies in the management of N 1 , N 2 , T 3 stage carcinoma of the lung, we analyzed results of treatment in 148 of 166 patients who were registered at the Massachusetts General Hospital Tumor Registry from 1971 to 1977 with a pathological diagnosis of N 1 , N 2 , T 3 carcinoma of the lung after pulmonary resection. Ninety-three patients received postoperative radiotherapy and another 55 were followed without further treatment. Patients with adenocarcinoma showed significant improvement of survival by postoperative radiotherapy; actuarial NED (no evidence of disease) survival rates were 85% and 51% at 1 year, and 43% and 8% at 5 years for S + RT (patients treated with surgery plus postoperative radiotherapy) and S (patients treated with surgery only) groups, respectively, (P 2 , T 3 stages. Regional recurrence was the most common failure in squamous cell carcinoma; 76% (13/17) and 45% (10/22) of all failures were in the regional area in S and S + RT groups. Regional failure in S + RT group was noted with radiation dose up to 5000 rad (TDF 82) which suggests radiation dose higher than 5000 rad in future trial

Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

International Nuclear Information System (INIS)

Bièche, Ivan; Girault, Igor; Urbain, Estelle; Tozlu, Sengül; Lidereau, Rosette

2004-01-01

Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability. To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. Relevant genes were further investigated in a well-defined cohort of 97 ERα-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. Seven of the 27 genes showed very weak or undetectable expression in both normal and tumoral breast tissues. Among the 20 remaining genes, seven genes (CYP2A6, CYP2B6, FMO5, NAT1, SULT2B1, GSTM3 and ABCC11) showed significantly higher mRNA levels in ERα-positive breast tumors than in normal breast tissue, or showed higher mRNA levels in ERα-positive breast tumors than in ERα-negative breast tumors. In the 97 ERα-positive breast tumor series, most alterations of these seven genes corresponded to upregulations as compared with normal breast tissue, with an incidence ranging from 25% (CYP2A6) to 79% (NAT1). Downregulation was rare. CYP2A6, CYP2B6, FMO5 and NAT1 emerged as new putative ERα-responsive genes in human breast cancer. Relapse-free survival was longer among patients with FMO5-overexpressing tumors or NAT1-overexpressing tumors (P = 0.0066 and P = 0.000052, respectively), but only NAT1 status retained prognostic significance in Cox multivariate regression analysis (P = 0.0013). Taken together, these data point to a role of genes coding for xenobiotic-metabolizing enzymes in breast tumorigenesis, NAT1 being an

Postoperative opioid analgesia: time for a reconsideration?

DEFF Research Database (Denmark)

Kehlet, H; Rung, G W; Callesen, T

1996-01-01

Postoperative pain relief has improved in recent years with the development of new analgesics, additional routes of administration and the appearance of the hypothesis of preemptive as well as balanced analgesia (Kehlet H; Postoperative pain relief-what is the issue? Br J Anaesth 1994;72:375-8). ......Postoperative pain relief has improved in recent years with the development of new analgesics, additional routes of administration and the appearance of the hypothesis of preemptive as well as balanced analgesia (Kehlet H; Postoperative pain relief-what is the issue? Br J Anaesth 1994......;72:375-8). Many initial improvements simply involved the administration of opioid analgesics in new ways, such as continuous or on demand intravenous (i.v.) or epidural infusion. These methods allow lower total opioid dosages, provide a more stable concentration of opioid at the receptor and correspondingly...

Predictors of Post-operative Mycetoma Recurrence Using Machine-Learning Algorithms: The Mycetoma Research Center Experience.

Directory of Open Access Journals (Sweden)

Ali Wadal

2016-10-01

Full Text Available Post-operative recurrence in mycetoma after adequate medical and surgical treatment is common and a serious problem. It has health, socio-economic and psychological detrimental effects on patients and families. It is with this in mind, we set out to determine the predictors of post-operative recurrence in mycetoma. The study included 1013 patients with Madurella mycetomatis causing eumycetoma who underwent surgical excision at the Mycetoma Research Centre, Khartoum, Sudan in the period 1991-2015. The clinical records of these patients were reviewed and relevant information was collected using a pre-designed data collection sheet. The study showed, 276 patients (27.2% of the studied population developed post-operative recurrence, 217 were males (78.6% and 59 were females (21.4%. Their age ranged between 5 to 70 years with a mean of 32 years. The disease duration at presentation ranged between 2 months and 17 years. The majority of the patients 118 (42.8% had mycetoma of 1 year duration. In this study, students were the most affected; 105 (38% followed by workers 70 (25.4%, then farmers 48(17.3%. The majority of the patients were from the Central Sudan 207 (75%, Western Sudan 53 (19.2% while 11 patients (4% were from the Northern part. Past history of surgical intervention performed elsewhere was reported in 196 patients (71.1%. Family history of mycetoma was reported in 50 patients (18.1%. The foot was the most affected site, 245 (88.7%, followed by the hand seen in 19 (6.8% patients and 44 (4.5% had different sites involvement. Most of the patients 258 (93.5% had wide local surgical excisions while 18 had major amputation. The model predicted that the certain groups have a high risk of recurrence, and these include patients with disease duration greater than 10 years and extra-pedal mycetoma. Patients with disease duration between [5-10] years, with pedal mycetoma, who had previous surgery, with positive family history and underwent wide local

Post-Operative Infection Is an Independent Risk Factor for Worse Long-Term Survival after Colorectal Cancer Surgery.

Science.gov (United States)

Kerin Povšič, Milena; Ihan, Alojz; Beovič, Bojana

2016-12-01

Colorectal cancer surgery is associated with a high incidence of post-operative infections, the outcome of which may be improved if diagnosed and treated early enough. We compared white blood cell (WBC) count, C-reactive protein (CRP), and procalcitonin (PCT) as predictors of post-operative infections and analyzed their impact on long-term survival. This retrospective study included 186 patients undergoing colorectal surgery. Post-operative values of WBC, CRP, and PCT were analyzed by the receiver operating characteristic (ROC) analysis. We followed infections 30 d after the surgery. A five-year survival was analyzed by Kaplan-Meier method and prognostic factors by Cox regression model. Fifty-five patients (29.5%) developed post-operative infection, the most frequent of which was surgical site infection (SSI). C-reactive protein on post-operative day three and PCT on post-operative day two demonstrated the highest diagnostic accuracy for infection (area under the curve [AUC] 0.739 and 0.735). C-reactive protein on post-operative day three was an independent predictor of infection. Five-year survival was higher in the non-infected group (70.8%), compared with the infected group (52.1%). The worst survival (40.9%) was identified in patients with organ/space SSI. Post-operative infection and tumor stage III-IV were independent predictors of a worse five-year survival. C-reactive protein on post-operative day three and PCT on post-operative day two may be early predictors of infection after colorectal cancer surgery. Post-operative infections in particular organ/space SSI have a negative impact on long-term survival.

Long-term Changes in Pulmonary Function After Incidental Lung Irradiation for Breast Cancer: A Prospective Study With 7-Year Follow-up

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Jaen, Javier, E-mail: javier.jaen.sspa@juntadeandalucia.es [Unidad de Atencion Integral al Cancer, Hospital Universitario Puerta del Mar, Cadiz (Spain); Vazquez, Gonzalo [Servicio de Oncologia Radioterapica, Hospital Clinico San Carlos, Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC), Madrid (Spain); Alonso, Enrique; De Las Penas, Maria D.; Diaz, Laura [Unidad de Atencion Integral al Cancer, Hospital Universitario Puerta del Mar, Cadiz (Spain); De Las Heras, Manuel [Servicio de Oncologia Radioterapica, Hospital Clinico San Carlos, Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC), Madrid (Spain); Perez-Regadera, Jose F. [Servicio de Oncologia Radioterapica, Hospital Universitario Doce de Octubre, Madrid (Spain)

2012-12-01

Purpose: To evaluate late pulmonary function changes after incidental pulmonary irradiation for breast cancer. Methods and Materials: Forty-three consecutive female patients diagnosed with breast carcinoma and treated with postoperative radiation therapy (RT) at the same dose (50 Gy) and fractionation (2 Gy/fraction, 5 days/week) were enrolled. Pulmonary function tests (PFT) and ventilation/perfusion scans were performed before RT and 6, 12, 24, and 84 months afterward. Results: Forty-one patients, mean age 55 years, were eligible for the analysis. No differences were found in the baseline PFT values for age, smoking status and previous chemotherapy; women undergoing mastectomy showed baseline spirometric PFT values lower than did women treated with conservative surgery. The mean pulmonary dose was 10.9 Gy, being higher in women who also received lymph node RT (15.8 vs 8.6, P<.01). Only 1 patient experienced symptomatic pneumonitis. All PFT values showed a reduction at 6 months. From then on, the forced vital capacity and forced expiratory volume in 1 second began their recovery until reaching, and even exceeding, their baseline values at 7 years. Diffusing capacity of the lungs for carbon monoxide and ventilation/perfusion scans continued to reduce for 24 months and then partially recovered their baseline values (-3.5%, -3.8%, and -5.5%, respectively). Only the percentage difference at 7 years in the ventilation scan correlated with the dosimetric parameters studied. Other variables, such as age, smoking status, previous chemotherapy, and concomitant tamoxifen showed no significant relation with changes in PFT ({Delta}PFT) values at 7 years. Conclusions: The study of reproducible subclinical parameters, such as PFT values, shows how their figures decrease in the first 2 years but practically recover their baseline values in the long term. The extent of the reduction in PFT values was small, and there was no clear association with several dosimetric and clinical

Impact of exercise pulmonary hypertension on postoperative outcome in primary mitral regurgitation.

Science.gov (United States)

Magne, Julien; Donal, Erwan; Mahjoub, Haifa; Miltner, Beatrice; Dulgheru, Raluca; Thebault, Christophe; Pierard, Luc A; Pibarot, Philippe; Lancellotti, Patrizio

2015-03-01

The management of asymptomatic patients with mitral regurgitation (MR) remains controversial. Exercise-induced pulmonary hypertension (ExPHT) was recently reported as a strong predictor of rapid onset of symptoms. We hypothesised that ExPHT is a predictor of postoperative cardiovascular events in patients with primary MR. One hundred and two patients with primary MR, no or mild symptoms (New York heart association (NYHA) ≤2), and no LV dysfunction/dilatation, were prospectively recruited in 3 centres and underwent exercise-stress echocardiography. The presence of ExPHT was defined as an exercise systolic pulmonary arterial pressure >60 mm Hg. All patients were closely followed up and operated on when indication for surgery was reached. Postoperative events were defined as the occurrence of atrial fibrillation (AF), stroke, cardiac-related hospitalisation or death. Among the 102 patients included, 59 developed ExPHT (58%). These patients were significantly older than those without ExPHT (p=0.01). During a mean postoperative follow-up of 50±23 months, 28 patients (26%) experienced a predefined cardiovascular event. Patients with ExPHT had significantly higher rate of postoperative events (39% vs 12%, p=0.005); the rate of events was still higher in these patients (32% vs 9%, p=0.013), even when excluding early postoperative AF (ie, within 48 h). Event-free survival was significantly lower in the ExPHT group (all events: 5-year: 60±8% vs 88±5%, p=0.007, events without early AF: 5-year: 67±7% vs 90±4%, p=0.02). Using Cox multivariable analysis, ExPHT remained independently associated with higher risk of postoperative events in all models (all p≤0.04). ExPHT is associated with increased risk of adverse cardiac events following mitral valve surgery in patients with primary MR. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Prospective Evaluation of Two iStent® Trabecular Stents, One iStent Supra® Suprachoroidal Stent, and Postoperative Prostaglandin in Refractory Glaucoma: 4-year Outcomes.

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Myers, Jonathan S; Masood, Imran; Hornbeak, Dana M; Belda, Jose I; Auffarth, Gerd; Jünemann, Anselm; Giamporcaro, Jane Ellen; Martinez-de-la-Casa, Jose M; Ahmed, Iqbal Ike K; Voskanyan, Lilit; Katz, L Jay

2018-03-01

This study evaluates long-term outcomes of two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin in eyes with refractory open angle glaucoma (OAG). Prospective ongoing 5-year study of 80 eligible subjects (70 with 4-year follow-up) with OAG and IOP ≥ 18 mmHg after prior trabeculectomy and while taking 1-3 glaucoma medications. Subjects received two iStent ® trabecular micro-bypass stents, one iStent Supra ® suprachoroidal stent, and postoperative travoprost. Postoperative IOP was measured with medication and annually following medication washouts. Performance was measured by the proportion of eyes with ≥ 20% IOP reduction on one medication (the protocol-specified prostaglandin) versus preoperative medicated IOP (primary outcome); and the proportion of eyes with postoperative IOP ≤ 15 and ≤ 18 mmHg on one medication (secondary outcome). Additional clinical and safety data included medications, visual field, pachymetry, gonioscopy, adverse events, visual acuity, and slit-lamp and fundus examinations. Preoperatively, mean medicated IOP was 22.0 ± 3.1 mmHg on 1.2 ± 0.4 medications, and mean unmedicated IOP was 26.4 ± 2.4 mmHg. Postoperatively, among eyes without later cataract surgery, mean medicated IOP at all visits through 48 months was ≤ 13.7 mmHg (≥ 37% reduction), and annual unmedicated IOP was ≤ 18.4 mmHg (reductions of ≥ 30% vs. preoperative unmedicated IOP and ≥ 16% vs. preoperative medicated IOP). At all postoperative visits among eyes without additional surgery or medication, ≥ 91% of eyes had ≥ 20% IOP reduction on one medication versus preoperative medicated IOP. At month 48, 97 and 98% of eyes achieved IOP ≤ 15 and ≤ 18 mmHg, respectively, on one medication. Six eyes required additional medication, no eyes required additional glaucoma surgery, and safety measurements were favorable throughout follow-up. IOP control was achieved safely with two

Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer

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Dauchy, Robert T.; Xiang, Shulin; Mao, Lulu; Brimer, Samantha; Wren, Melissa A.; Yuan, Lin; Anbalagan, Muralidharan; Hauch, Adam; Frasch, Tripp; Rowan, Brian G.; Blask, David E.; Hill, Steven M.

2014-01-01

Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to anti-estrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of ERα+ MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speeds the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characters were not produced in animals where circadian rhythms were not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to re-establish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen. PMID:25062775

Postoperative nausea and vomiting in pediatric anesthesia.

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Höhne, Claudia

2014-06-01

Postoperative nausea and vomiting (PONV) has a high incidence in children and requires prophylactic and therapeutic strategies. PONV can be reduced by the avoidance of nitrous oxide, volatile anesthetics, and the reduction of postoperative opioids. The use of dexamethasone, 5-HT3 antagonists, or droperidol alone is potent, but combinations are even more effective to reduce PONV. Droperidol has a Food and Drug Administration warning. Hence, dexamethasone and 5-HT3 antagonists should be preferred as prophylactic drugs. It is further reasonable to adapt PONV prophylaxis to different risk levels. Prolonged surgery time, inpatients, types of surgery (e.g. strabismus and ear-nose-throat surgery), and patients with PONV in history should be treated as high risk, whereas short procedures and outpatients are to be treated as low risk. Concluding from the existing guidelines and data on the handling of PONV in children at least 3 years, the following recommendations are given: outpatients undergoing small procedures should receive a single prophylaxis, outpatients at high risk a double prophylaxis, inpatients with surgery time of more than 30 min and use of postoperative opioids should get double prophylaxis, and inpatients receiving a high-risk surgical procedure or with other risk factors a triple prophylaxis (two drugs and total intravenous anesthesia). Dimenhydrinate can be used as a second choice, whereas droperidol and metoclopramide can only be recommended as rescue therapy.

Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: their antioxidant effect and role of estrogen receptor alpha.

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Mosquera, Laurivette; Colón, Jennifer M; Santiago, José M; Torrado, Aranza I; Meléndez, Margarita; Segarra, Annabell C; Rodríguez-Orengo, José F; Miranda, Jorge D

2014-05-02

17β-Estradiol is a multi-active steroid that imparts neuroprotection via diverse mechanisms of action. However, its role as a neuroprotective agent after spinal cord injury (SCI), or the involvement of the estrogen receptor-alpha (ER-α) in locomotor recovery, is still a subject of much debate. In this study, we evaluated the effects of estradiol and of Tamoxifen (an estrogen receptor mixed agonist/antagonist) on locomotor recovery following SCI. To control estradiol cyclical variability, ovariectomized female rats received empty or estradiol filled implants, prior to a moderate contusion to the spinal cord. Estradiol improved locomotor function at 7, 14, 21, and 28 days post injury (DPI), when compared to control groups (measured with the BBB open field test). This effect was ER-α mediated, because functional recovery was blocked with an ER-α antagonist. We also observed that ER-α was up-regulated after SCI. Long-term treatment (28 DPI) with estradiol and Tamoxifen reduced the extent of the lesion cavity, an effect also mediated by ER-α. The antioxidant effects of estradiol were seen acutely at 2 DPI but not at 28 DPI, and this acute effect was not receptor mediated. Rats treated with Tamoxifen recovered some locomotor activity at 21 and 28 DPI, which could be related to the antioxidant protection seen at these time points. These results show that estradiol improves functional outcome, and these protective effects are mediated by the ER-α dependent and independent-mechanisms. Tamoxifen׳s effects during late stages of SCI support the use of this drug as a long-term alternative treatment for this condition. Copyright © 2014 Elsevier B.V. All rights reserved.

POSTOPERATIVE TREATMENT OF THYROID CANCER WITH RADIOACTIVE IODINE

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Blahd, William H.; Koplowitz, Jerry M.

1963-06-15

Experiences in the postoperative treatment of thyroid cancer with radioactive iodine since 1949 are reviewed. Forty-five patients received therapeutic amounts of I/sup 131/ and were followed for more than one year. Cancer metastases were localized by means of the mechanical scintiscanner after patients had received large tracer doses of I/sup 131/ preceded by injections of thyrotropic hormone. A consistent therapeutic regimen was followed involving four basic modalities of therapy: surgical thyroidectomy, thyrotropic hormone stimulation, cancerocidal doses of I/sup 131/ and thyroid extract administration. Twenty-nine patients in the series had proved metastatic lesions; 11 died, 18 are living, and 41% have lived 5 or more years. All patients who were free of metastases after initial thyroid surgery are alive. No complications from I/sup 131/ therapy were observed. This is attributed to the conservative dosage regimen employed. The results of the use of I/sup 131/ in the postoperative treatment of thyroid cancer in other reported series are also reviewed. (P.C.H.)

Postoperative analgesia in children when using clonidine in addition ...

African Journals Online (AJOL)

The aim of the study was to evaluate the efficacy of clonidine in association with fentanyl as an additive to bupivacaine 0.25% given via single shot caudal epidural in pediatric patients for postoperative pain relief. In the present prospective randomized double blind study, 40 children of ASA-I-II aged 1-5 years scheduled for ...

Internal fixation of mandibular angle fractures using one miniplate in Greek children: a 5-year retrospective study.

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Iatrou, Ioannis; Theologie-Lygidakis, Nadia; Tzermpos, Fotios; Kamperos, Georgios

2015-01-01

Treatment modalities of mandibular angle fractures (MAFs) have been analyzed in several studies mainly referring to adult populations. The aim of this study was to retrospectively present and discuss our experience and literature findings regarding the treatment of MAFs in children. Data were retrieved from the files of the Oral and Maxillofacial department, at the Children's Hospital ''P. & A. Kyriakou'' of Athens, during a 5 years period (2009-2013). Demographic features, treatment methods, outcome and follow-up of all patients with mandibular angle fractures were recorded. 6 boys, 5-14 years old (mean age 10 years), were included in the study. They were all treated intraorally with open reduction and fixation via one monocortical titanium plate osteosynthesis at the external oblique line of the mandible, followed by 1 week of intermaxillary fixation (IMF). Plates were removed 3-12 months post-operatively. Follow-up period ranged from 12 to 18 months (mean 14.7 months). All fractures healed uneventfully and the patients tolerated well both the operation and the post-operative period. Osteosynthesis via intraoral approach combined with short duration IMF is adequate in treating MAFs in children. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Minimal clinically important improvement (MCII) and patient-acceptable symptom state (PASS) in total hip arthroplasty (THA) patients 1 year postoperatively

DEFF Research Database (Denmark)

Paulsen, Aksel; Roos, Ewa M.; Pedersen, Alma Becic

2014-01-01

-55% improvement from mean baseline PRO score and PASSs corresponded to absolute follow-up scores of 57-91% of the maximum score in THA patients 1 year after surgery. Interpretation - This study improves the interpretability of PRO scores. The different estimation approaches presented may serve as a guide......Background and purpose - The increased use of patient-reported outcomes (PROs) in orthopedics requires data on estimated minimal clinically important improvements (MCIIs) and patient-acceptable symptom states (PASSs). We wanted to find cut-points corresponding to minimal clinically important PRO...... change score and the acceptable postoperative PRO score, by estimating MCII and PASS 1 year after total hip arthroplasty (THA) for the Hip Dysfunction and Osteoarthritis Outcome Score (HOOS) and the EQ-5D. Patients and methods - THA patients from 16 different departments received 2 PROs and additional...

The EPOS-CC Score: An Integration of Independent, Tumor- and Patient-Associated Risk Factors to Predict 5-years Overall Survival Following Colorectal Cancer Surgery.

Science.gov (United States)

Haga, Yoshio; Ikejiri, Koji; Wada, Yasuo; Ikenaga, Masakazu; Koike, Shoichiro; Nakamura, Seiji; Koseki, Masato

2015-06-01

Surgical audit is an essential task for the estimation of postoperative outcome and comparison of quality of care. Previous studies on surgical audits focused on short-term outcomes, such as postoperative mortality. We propose a surgical audit evaluating long-term outcome following colorectal cancer surgery. The predictive model for this audit is designated as 'Estimation of Postoperative Overall Survival for Colorectal Cancer (EPOS-CC)'. Thirty-one tumor-related and physiological variables were prospectively collected in 889 patients undergoing elective resection for colorectal cancer between April 2005 and April 2007 in 16 Japanese hospitals. Postoperative overall survival was assessed over a 5-years period. The EPOS-CC score was established by selecting significant variables in a uni- and multivariate analysis and allocating a risk-adjusted multiplication factor to each variable using Cox regression analysis. For validation, the EPOS-CC score was compared to the predictive power of UICC stage. Inter-hospital variability of the observed-to-estimated 5-years survival was assessed to estimate quality of care. Among the 889 patients, 804 (90%) completed the 5-years follow-up. Univariate analysis displayed a significant correlation with 5-years survival for 14 physiological and nine tumor-related variables (p model for the prediction of survival. Risk-adjusted multiplication factors between 1.5 (distant metastasis) and 0.16 (serum sodium level) were accorded to the different variables. The predictive power of EPOS-CC was superior to the one of UICC stage; area under the curve 0.87, 95% CI 0.85-0.90 for EPOS-CC, and 0.80, 0.76-0.83 for UICC stage, p < 0.001. Quality of care did not differ between hospitals. The EPOS-CC score including the independent variables age, performance status, serum sodium level, TNM stage, and lymphatic invasion is superior to the UICC stage in the prediction of 5-years overall survival. This higher accuracy might be explained by the

Avaliação da Atividade Proliferativa no Epitélio Mamário Adjacente a Fibroadenoma em Mulheres Tratadas com Tamoxifeno Evaluation of Proliferative Activity in the Mammary Epithelium Adjacent to Fibroadenoma in Women Treated with Tamoxifen

Directory of Open Access Journals (Sweden)

Juarez Antônio de Sousa

2000-08-01

Full Text Available Objetivo: estudar a atividade proliferativa do epitélio mamário normal adjacente a fibroadenoma em mulheres na fase lútea do ciclo menstrual, tratadas com tamoxifeno. Pacientes e Métodos: estudou-se por técnica imuno-histoquímica, com o uso do anticorpo monoclonal MIB-1, a atividade proliferativa no epitélio mamário adjacente a fibroadenoma. O estudo foi randomizado e duplo-cego. As 44 mulheres com fibroadenoma foram divididas em 3 grupos: A (n = 16; placebo, B (n = 15; tamoxifeno, 10 mg e C (n = 13; tamoxifeno, 20 mg. O tamoxifeno foi utilizado por 22 dias, a partir do 2º dia do ciclo menstrual, e a biópsia realizada no 23º dia. Resultados: a porcentagem média de núcleos corados por 1000 células no grupo A foi 9,2, no grupo B, 4,5, e no grupo C, 3,2. O teste de Fisher revelou que o tamoxifeno reduziu de forma significante a imunoexpressão do MIB-1 nas doses de 10 e 20 mg em comparação com o grupo placebo (pPurpose: to study the monoclonal antibody MIB-1 in the normal breast epithelium adjacent to a fibroadenoma in women in the luteal phase of the menstrual cycle treated with tamoxifen. Patients and methods: the proliferative activity of the mammary epithelium adjacent to the fibroadenoma was studied by immunohistochemistry based on immunoexpression of the monoclonal antibody MIB-1. The study was randomized and double blind and was conducted on 44 women with fibroadenomas, divided into 3 groups: A (n = 16; placebo, B (n = 15; tamoxifen, 10 mg, and C (n = 13; tamoxifen, 20 mg. Tamoxifen was administered for 22 days starting on the 2nd day of the menstrual cycle and a biopsy was taken on the 23rd day. Results: the mean percentage of stained nuclei per 1000 cells was 9.2 in group A, 4.5 in group B, and 3.2 in group C. Fisher's test revealed that tamoxifen significantly reduced the immunoexpression of MIB-1 at the doses of 10 and 20 mg compared to the placebo group (p<0.0001, with no significant differences between doses in terms of

Risk factors for postoperative complications in robotic general surgery.

Science.gov (United States)

Fantola, Giovanni; Brunaud, Laurent; Nguyen-Thi, Phi-Linh; Germain, Adeline; Ayav, Ahmet; Bresler, Laurent

2017-03-01

The feasibility and safety of robotically assisted procedures in general surgery have been reported from various groups worldwide. Because postoperative complications may lead to longer hospital stays and higher costs overall, analysis of risk factors for postoperative surgical complications in this subset of patients is clinically relevant. The goal of this study was to identify risk factors for postoperative morbidity after robotic surgical procedures in general surgery. We performed an observational monocentric retrospective study. All consecutive robotic surgical procedures from November 2001 to December 2013 were included. One thousand consecutive general surgery patients met the inclusion criteria. The mean overall postoperative morbidity and major postoperative morbidity (Clavien >III) rates were 20.4 and 6 %, respectively. This included a conversion rate of 4.4 %, reoperation rate of 4.5 %, and mortality rate of 0.2 %. Multivariate analysis showed that ASA score >3 [OR 1.7; 95 % CI (1.2-2.4)], hematocrit value surgery [OR 1.5; 95 % CI (1-2)], advanced dissection [OR 5.8; 95 % CI (3.1-10.6)], and multiquadrant surgery [OR 2.5; 95 % CI (1.7-3.8)] remained independent risk factors for overall postoperative morbidity. It also showed that advanced dissection [OR 4.4; 95 % CI (1.9-9.6)] and multiquadrant surgery [OR 4.4; 95 % CI (2.3-8.5)] remained independent risk factors for major postoperative morbidity (Clavien >III). This study identifies independent risk factors for postoperative overall and major morbidity in robotic general surgery. Because these factors independently impacted postoperative complications, we believe they could be taken into account in future studies comparing conventional versus robot-assisted laparoscopic procedures in general surgery.

Postoperative pain

DEFF Research Database (Denmark)

Kehlet, H; Dahl, J B

1993-01-01

also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree......Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...

Krüppel-like factor 5 is essential for proliferation and survival of mouse intestinal epithelial stem cells

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Mandayam O. Nandan

2015-01-01

Full Text Available Krüppel-like factor 5 (KLF5 is a pro-proliferative transcription factor that is expressed in dividing epithelial cells of the intestinal crypt. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5 has been identified as a stem cell marker in both small intestinal and colonic epithelial cells. To determine whether KLF5 regulates proliferation of intestinal stem cells, we investigated the effects of Klf5 deletion specifically from the intestinal stem cells in adult mice. Mice with inducible intestinal stem cell-specific deletion of Klf5 (Lgr5-Klf5fl/fl were injected with tamoxifen for 5 consecutive days to induce Lgr5-driven Cre expression. Intestinal and colonic tissues were examined by immunohistochemistry at various time points up to 112 days following start of tamoxifen treatment. Klf5 is co-localized in the crypt-based columnar (CBC cells that express Lgr5. By 11 days following the start of tamoxifen treatment, Lgr5-positive crypts from which Klf5 was deleted exhibited a loss of proliferation that was accompanied by an increase in apoptosis. Beginning at 14 days following the start of tamoxifen treatment, both Klf5 expression and proliferation were re-established in the transit-amplifying epithelial cells but not in the Lgr5-positive CBC cells. By 112 days post-treatment, up to 90% of the Lgr5-positive cells from which Klf5 was deleted were lost from the intestinal crypts. These results indicate a critical role for KLF5 in the survival and maintenance of intestinal stem cells.

The role of postoperative external irradiation for the incompletely resected meningiomas

International Nuclear Information System (INIS)

Kim, Tae Hyun; Yang, Dae Sik; Kim, Chul Young; Choi, Myung Sun

2000-01-01

The aim of this study is to look for the possible efficacy of postoperative external irradiation for incompletely resected meningiomas. From August 1981 to January 1997, forty-four patients with intracranial meningioma were treated by postoperative external irradiation. Of the 44 meningiomas, 18 transitional, 13 meningotheliomatous, 6 hemangiopericytic, 4 atypical, 2 fibroblastic and 1 malignant meningioma were identified. We classified all patients into two groups by the histology. The benign group was consisted of the meningotheliomatous, transitional and fibroblastic types. The malignant group was consisted of the atypical, hemangiopericytic and malignant types.In the means of surgery, 37 patients were resected incompletely and 7 patients were managed by biopsy only. After surgery, all patients were received postoperative external irradiation. Radiotherapy was delivered using Co-60 or 4 MV photon beam to a total dose of 50 to 66 Gy (mean dose:57.4 Gy) with a 1.8 to 2 Gy per fraction. The median follow-up was 48 months (range:21-101 months). Multivariate analysis of the influence by age, sex, location, histology and radiation dose on local control has been done using Cox's proportional hazard model. 5-year local control rate was 93.8% for the benign histology and 51.8% for the malignant histology (p=0.0110) and overall local control rate at 5 years was 87.4%. The analysis of the prognostic factors, such as age, sex, location, and radiation dose were not significant except for the histology. Adjuvant postoperative external irradiation appears to be significantly improved local control in the patients with incompletely resected meningiomas

Postoperative radiotherapy in salivary ductal carcinoma: a single institution experience

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Kim, Tae Hyung; Kim, Mi Sun; Choi, Seo Hee; Suh, Yang Gun; Koh, Yoon Woo; Kim, Se Hun; Choi, Eun Chang; Keum, Ki Chang [Yonsei University College of Medicine, Seoul (Korea, Republic of)

2014-09-15

We reviewed treatment outcomes and prognostic factors for patients with salivary ductal carcinoma (SDC) treated with surgery and postoperative radiotherapy from 2005 to 2012. A total of 16 patients were identified and 15 eligible patients were included in analysis. Median age was 61 years (range, 40 to 71 years) and 12 patients (80%) were men. Twelve patients (80%) had a tumor in the parotid gland, 9 (60%) had T3 or T4 disease, and 9 (60%) had positive nodal disease. All patients underwent surgery and postoperative radiotherapy. Postoperative radiotherapy was delivered using 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Locoregional failure-free survival (LRFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Differences in survival based on risk factors were tested using a log-rank test. Median total radiotherapy dose was 60 Gy (range, 52.5 to 63.6 Gy). Four patients received concurrent weekly chemotherapy with cisplatin. Among 10 patients who underwent surgery with neck dissection, 7 received modified radical neck dissection. With a median follow-up time of 38 months (range, 24 to 105 months), 4-year rates were 86% for LRFFS, 51% for DFFS, 46% for PFS, and 93% for OS. Local failure was observed in 2 patients (13%), and distant failure was observed in 7 (47%). The lung was the most common involved site of distant metastasis. Surgery and postoperative radiotherapy in SDC patients resulted in good local control, but high distant metastasis remained a major challenge.

Apolipoprotein D expression does not predict breast cancer recurrence among tamoxifen-treated patients

DEFF Research Database (Denmark)

Klebaner, Daniella; Hamilton-Dutoit, Stephen; Ahern, Thomas P

2017-01-01

confounding using logistic regression. RESULTS: Cytoplasmic ApoD expression was seen in 68% of ER+ tumors, in 66% of ER- tumors, and in 66% of controls across both groups. In women with ER+ tumors, the associations of cytoplasmic ApoD expression with recurrence (OR = 1.0; 95% CI = 0.7 to 1.4) and increasing...... cytoplasmic expression with recurrence (OR = 1.0; 95% CI = 0.996 to 1.003) were null, as were those for women with ER- tumors. Associations for nuclear ApoD expression and combined nuclear and cytoplasmic expression were similarly near-null. CONCLUSION: ApoD expression is likely not a predictor of recurrence......BACKGROUND: Apolipoprotein D (ApoD) has been proposed as a predictor of breast cancer recurrence among estrogen receptor-positive (ER+), tamoxifen-treated patients. METHODS: We conducted a population-based case-control study nested in a population of 11,251 women aged 35-69 years at diagnosis...

Classical prognostic factors in patients with non-advanced endometrial cancer treated with postoperative radiotherapy

International Nuclear Information System (INIS)

Karolewski, K.; Kojs, Z.; Jakubowicz, J.; Urbanski, K.; Michalak, A.

2006-01-01

Aim: Analysis of classical prognostic factors in patients with non-advanced endometrial cancer treated with postoperative radiotherapy. Materials/Methods: In the years 1985 - 1999, 705 patients underwent postoperative radiotherapy due to endometrial cancer: 529 patients with FIGO stage I and 176 with FIGO stage II cancer. Mean age was 58 years. In 96% of patients endometrioid adenocarcinoma was found. In 49.9% the cancer had a high, in 27.9% a medium, and in 22.2% a low degree of differentiation. Results: 82% of patients had 5-year disease-free survival. In univariate analysis a significantly higher rate of disease-free survival was observed in: patients younger than 60, with moderately and well differentiated cancers, with stage I endometrioid adenocarcinoma with less than 50% myometrial invasion. In multivariate analysis degree of cancer differentiation was the only independent prognostic factor. Conclusions: In a group of patients with non-advanced endometrial cancer treated with postoperative radiotherapy, degree of cancer differentiation is the primary prognostic factor. (authors)

Postoperative radiotherapy for adenocarcinoma of the ethmoid sinuses: treatment results for 47 patients

International Nuclear Information System (INIS)

Claus, Filip; Boterberg, Tom; Ost, Piet; Huys, John; Vermeersch, Hubert; Braems, Sabine; Bonte, Katrien; Moerman, Mieke; Verhoye, Christoph; Neve, Wilfried de

2002-01-01

Purpose: Ethmoid sinus cancer is a rare malignancy. Treatment results are mostly reported together with other sinonasal tumors, grouping a wide range of different histologies and treatment approaches. This study reports on the treatment outcome of 47 patients diagnosed with adenocarcinoma of the ethmoid sinuses and treated with surgery and high-dose postoperative radiation therapy. Methods and Materials: Between September 1985 and October 2001, 51 patients with adenocarcinoma of the ethmoid sinuses were referred to the Ghent University Hospital. Four patients were treated with low-dose palliative radiation because of very extended inoperable disease or distant metastasis at the time of diagnosis. They were not included in this analysis. The other 47 patients, all staged as N0M0, were treated with surgery and postoperative high-dose radiation therapy. The median follow-up was 32 months. The T-stages were T1 for 2, T2 for 17, T3 for 11, and T4 for 17 patients. All 47 patients were staged as N0M0. Results: The 3-year, 5-year, and 7-year overall survival are respectively 71%, 60%, and 38%. The 3-year and 5-year disease-free survival are respectively 62% and 36%. The 3-year and 5-year disease-free survival for T1-T2 stages are respectively 87% and 55%, for T3 stages 57% and 28%, and for T4 stages 41% and 25%. The locoregional tumor control was 70% and 59% at respectively 3 and 5 years. Patients presenting with intracranial tumor invasion at the time of diagnosis relapsed within 7 months after the end of radiotherapy. Radiation-induced severe dry eye syndrome and optic neuropathy was observed in respectively 7 and 2 of the 47 cases. Conclusion: Postoperative radiotherapy for adenocarcinoma of the ethmoid sinuses is associated with good local control rates. Crucial for a favorable prognosis is the absence of intracranial invasion. The rarity of these tumors makes it difficult to evaluate new therapeutic advances

Does Histologic Subtype Influence the Post-Operative Outcome in Spinal Meningioma?

Science.gov (United States)

Zham, Hanieh; Moradi, Afshin; Rakhshan, Azadeh; Zali, Alireza; Rahbari, Ali; Raee, Mohammadreza; Ashrafi, Farzad; Ahadi, Mahsa; Larijani, Leila; Baikpour, Masoud; Khayamzadeh, Maryam

2016-04-01

Postoperative outcome of spinal meningiomas is an important issue in surgery decision-making. There are limited and conflicting data in the literature about the prognostic factors influencing recovery, especially about the histopathologic subtypes. This study was carried out to evaluate the effect of some of these factors on postoperative outcome. This study was performed on 39 patients operated for spinal meningioma between October 1998 and January 2012; their histopathologic subtype was determined according to WHO criteria. The follow up period ranged between 8 - 120 months. The influence of histopathologic subtype, grade, age, sex, surgical approach, local adhesion and anatomical location was assessed according to Frankel classification of neurologic deficit. From a total number of 39 spinal meningiomas, 34 cases were WHO grade I, from which 15 cases were psammomatous, 7 cases were meningothelial, 9 cases were transitional and 3 cases were fibroblastic. Five cases were grade II, 3 of which had clear cell appearance and the remaining 2 had chordoid appearance. The mean age was 51.6 (22 to 76) years; 25 cases were female and 14 cases were male. This study revealed that grade II meningioma cases had poor prognosis in all 5 cases and psammomatous subtype had poor postoperative outcome in 40% of cases while the other subtypes had good outcome in all cases (P = 0.026). Cervical location of the tumor was also related with poor outcome in 37.5% of the cases, while 22.5% had poor outcome in other locations (P = 0.029). Age below and above 45 years and sex had no significant influence on the outcome. Spinal meningiomas of psammomatous type and grade II spinal meningiomas are associated with less favorable postoperative neurologic outcome. Cervical location has also a negative correlation with a good outcome.

Post-operative delirium is an independent predictor of 30-day hospital readmission after spine surgery in the elderly (≥65years old): A study of 453 consecutive elderly spine surgery patients.

Science.gov (United States)

Elsamadicy, Aladine A; Wang, Timothy Y; Back, Adam G; Lydon, Emily; Reddy, Gireesh B; Karikari, Isaac O; Gottfried, Oren N

2017-07-01

In the last decade, costs of U.S. healthcare expenditures have been soaring, with billions of dollars spent on hospital readmissions. Identifying causes and risk factors can reduce soaring readmission rates and help lower healthcare costs. The aim of this is to determine if post-operative delirium in the elderly is an independent risk factor for 30-day hospital readmission after spine surgery. The medical records of 453 consecutive elderly (≥65years old) patients undergoing spine surgery at Duke University Medical Center from 2008 to 2010 were reviewed. We identified 17 (3.75%) patients who experienced post-operative delirium according to DSM-V criteria. Patient demographics, comorbidities, and post-operative complication rates were collected for each patient. Elderly patients experiencing post-operative delirium had an increased length of hospital stay (10.47days vs. 5.70days, p=0.009). Complication rates were similar between the cohorts with the post-operative delirium patients having increased UTI and superficial surgical site infections. In total, 12.14% of patients were re-admitted within 30-days of discharge, with post-operative delirium patients experiencing approximately a 4-fold increase in 30-day readmission rates (Delirium: 41.18% vs. No Delirium: 11.01%, p=0.002). In a multivariate logistic regression analysis, post-operative delirium is an independent predictor of 30-day readmission after spine surgery in the elderly (p=0.03). Elderly patients experiencing post-operative delirium after spine surgery is an independent risk factor for unplanned readmission within 30-days of discharge. Preventable measures and early awareness of post-operative delirium in the elderly may help reduce readmission rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immediate Postoperative Alignment Following Bimedial Rectus Recession for Esotropia in Children Compared to Adults.

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Hassan, Mohamed B; Diehl, Nancy N; Mohney, Brian G

2018-06-18

To determine whether the immediate postoperative alignment among patients undergoing successful bilateral weakening surgery for esotropia is different in children compared to adults. The medical records of all patients undergoing surgery for esotropia by a single surgeon at a major academic referral center between January 1, 2002, and July 1, 2014 (n = 544), were retrospectively reviewed. Exclusion criteria included those with prior strabismus surgery, unilateral surgery, strengthening procedures, vertical or superior oblique surgery, and those wearing hyperopic spectacles for accommodative esotropia. Additionally, all patients had to have a 1- and 6-week postoperative examination and 8 prism diopters (PD) or less of deviation at their 6-week examination. Ninety-five (17.5%) of the 544 patients met the inclusion criteria. Surgery was performed at a median age of 3.7 years (range: 7 months to 86 years) for a median esodeviation of 35 PD (range: 12 to 70 PD). Among the 73 patients younger than 11 years, the immediate mean postoperative alignment was 9 PD of exotropia (range: 14 PD esotropia to 30 PD exotropia) compared to 2 PD of exotropia (range: 9 PD esotropia to 30 PD exotropia) in the 22 patients 11 years or older (P = .001). Seventy-one percent of successfully aligned patients younger than 11 years were exotropic in the immediate postoperative week compared to 23% of those 11 years or older (P XXXX.]. Copyright 2018, SLACK Incorporated.

Haloperidol prophylaxis for preventing aggravation of postoperative delirium in elderly patients: a randomized, open-label prospective trial.

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Fukata, Shinji; Kawabata, Yasuji; Fujishiro, Ken; Kitagawa, Yuichi; Kuroiwa, Kojiro; Akiyama, Hirotoshi; Takemura, Marie; Ando, Masahiko; Hattori, Hideyuki

2017-07-01

The aim of this study was to evaluate the safety and efficacy of the early administration haloperidol in preventing the aggravation of postoperative delirium in elderly patients. A total of 201 patients (age ≥75 years) who underwent elective surgery were enrolled. The patients were divided into two groups: the intervention group (n = 101) received prophylactic haloperidol (5 mg); the control group (n = 100) did not. Haloperidol was administered daily during postoperative days 0-5 to the patients who presented with NEECHAM scores of 20-24 when measured at 18:00. The primary endpoint was the incidence of severe postoperative delirium. The incidence of severe postoperative delirium in all patients was 25.1%. The incidence of severe postoperative delirium in the intervention group (18.2%) was significantly lower than that in the control group (32.0%) (p = 0.02). The difference between the two groups was larger when the analysis was limited to the 70 patients who had NEECHAM scores of 20-24 for at least one day during postoperative days 0-5. No adverse effects of the haloperidol were observed. The prophylactic administration of haloperidol at the early stage of delirium significantly reduced the incidence of severe postoperative delirium in elderly patients. Clinical Trial Registration UMIN000007204.

Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

African Journals Online (AJOL)

2017-12-05

Dec 5, 2017 ... systemic diseases (hypertension, type 2 diabetes mellitus),. Original Article. INTRODUCTION. Postoperative ... vertigo, etc.) have been shown.[3-15]. In this study, we aimed to investigate possible relationship between preoperative NLR and postoperative pain (which was evaluated by analgesic demand at.

The Auckland Cataract Study: 2 year postoperative assessment of aspects of clinical, visual, corneal topographic and satisfaction outcomes

Science.gov (United States)

Thompson, A M; Sachdev, N; Wong, T; Riley, A F; Grupcheva, C N; McGhee, C N

2004-01-01

Aim: To assess clinical, visual, computerised corneal topographic, and subjective satisfaction with visual acuity, in a cohort of subjects 2 years after phacoemulsification surgery in a public hospital in New Zealand. Methods: Prospective study of a representative sample of 97 subjects (20%) randomly selected from 480 subjects in the original Auckland Cataract Study (ACS) cohort. The clinical assessment protocol was identical to the ACS and included an extensive questionnaire to enable direct comparisons to be made between the two groups. Results: The study population was predominantly female (66%) with a mean age of 76.3 (SD 9.9) years. New systemic and ocular disease affected 18.4% and 10.3% of subjects respectively, and 10.3% required referral to either a general practitioner (2.1%) or ophthalmologist (8.2%). Mean best spectacle corrected visual acuity (BSCVA) was 0.2 (0.2) logMAR units (6/9 Snellen equivalent), with mean spherical equivalent −0.37 (1.01) dioptres (D) and astigmatism −1.07 (0.70) D 2 years postoperatively, compared to mean BSCVA 0.1 (0.2) logMAR units (6/7.5 Snellen equivalent), spherical equivalent −0.59 (1.07) D, and astigmatism −1.14 (0.77) D 4 weeks after surgery. 94.9% of subjects retained a BSCVA of 6/12 or better, irrespective of pre-existing ocular disease. The overall posterior capsule opacification (PCO) rate was 20.4% and this was visually insignificant in all but 3.1% of eyes that had already undergone Nd:YAG posterior capsulotomy. Orbscan II elevation technology demonstrated corneal stability 2 years after uncomplicated phacoemulsification. Although corneal astigmatism was eliminated in approximately half of the subjects 1 month postoperatively, astigmatism showed a tendency to regress towards the preoperative level with local corneal thickening at the site of incision 2 years after cataract surgery. Of fellow eyes, 61.2% had undergone cataract surgery. Overall, 75.3% of subjects were moderately to very satisfied with their

Results of proximal gastric vagotomy over 1-5 years in a district general hospital.

Science.gov (United States)

Makey, D A; Tovey, F I; Heald, R J

1979-01-01

One hundred and seventy-three underwent proximal gastric vagotomy for duodenal ulceration over a 6-year period. One hundred and fifteen of these have been followed up for 1-5 years. The operative mortality was nil and the result was satisfactory in 91 per cent. The incidence of side effects was small, notably that of dumping being 2.4 per cent and of diarrhoea, 3.6 per cent. Incidence of postoperative heartburn was reduced from 13 per cent to 4 per cent by the introduction of hepatic interposition. The incidence of recurrent ulceration was 5.1 per cent after an average interval of 2 years and that of new gastric ulceration 2.6 per cent after an average of 4 years. There were no recurrent ulcers in those who had peroperative Burge tests, although secretory studies showed no difference between those tested and those not tested. Most recurrences occurred in the earliest cases operated on before Burge testing was introduced and when only 2 cm of the lower oesophagus were exposed.

Epidural morphine for postoperative pain relief in children

DEFF Research Database (Denmark)

Henneberg, S W; Hole, P; Haas, Inge Madsen De

1993-01-01

Epidural morphine for postoperative pain relief is in general use, and has proved to be very efficient in adults. The epidural technique and the use of epidural morphine are much less frequent in children. For 2 years we have prospectively followed 76 children who had epidural morphine...... for postoperative pain relief after major abdominal surgery. The age distribution was from newborn to 13 years, with a median age of 12 months. It was estimated that 94% of the patients had good analgesia for the first 24 postoperative hours and no other opioids were given. The side effects were few, but one case...... the investigation. We observed a change in the sleeping pattern with an increased number of sleep-induced myoclonia during the administration of epidural morphine. In conclusion, the use of epidural morphine in children for postoperative pain relief is very efficient. The minimal effective dose has not been...

Postoperative pyoderma gangrenosum: A rare complication after appendectomy

Directory of Open Access Journals (Sweden)

G Faghihi

2015-01-01

Full Text Available Pyoderma gangrenosum (PG is an uncommon inflammatory ulcerative skin disease. It is characterized by painful progressive necrosis of the wound margins. Rarely, postoperative pyoderma gangrenosum (PPG manifests as a severe disturbance of wound healing following surgical interventions. Only rare cases of this complication have been reported after appendectomy. We report a case of PPG in a 29-year-old female after appendectomy. She was successfully treated with oral prednisolone. Postoperative pyoderma gangrenosum should be kept in mind in the differential diagnosis of any postoperative delayed wound healing, because this disease is simply distinguished from a postoperative wound.

Postoperative pyoderma gangrenosum: A rare complication after appendectomy

Science.gov (United States)

Faghihi, G; Abtahi-Naeini, B; Nikyar, Z; Jamshidi, K; Bahrami, A

2015-01-01

Pyoderma gangrenosum (PG) is an uncommon inflammatory ulcerative skin disease. It is characterized by painful progressive necrosis of the wound margins. Rarely, postoperative pyoderma gangrenosum (PPG) manifests as a severe disturbance of wound healing following surgical interventions. Only rare cases of this complication have been reported after appendectomy. We report a case of PPG in a 29-year-old female after appendectomy. She was successfully treated with oral prednisolone. Postoperative pyoderma gangrenosum should be kept in mind in the differential diagnosis of any postoperative delayed wound healing, because this disease is simply distinguished from a postoperative wound. PMID:25511218

Significance of postoperative irradiation for breast cancer

International Nuclear Information System (INIS)

Murai, Nobuko; Ogami, Koji; Nishikawa, Kiyoshi; Koga, Kenji; Waki, Norio; Higashi, Hidefumi; Hayashi, Asami; Shibata, Koichiro; Watanabe, Katsuji

1986-01-01

From 1978 through 1983, 27 patients were treated with surgery followed by irradiation (irradiated group) and 29 with surery alone (non-irradiated group). In the irradiated group, 10 had stage II and 17 stage III; in the non-irradiated group, 25 had stage II and 4 stage III. The most common histology was medullary tubular carcinoma (MTC). There was no significant difference in survivals at 3 years and 5 years between the groups. Similarly, no significant difference was seen among stage II patients. Patients with MTC tended to have worse survivals in the irradiated group than in the non-irradiated group, with no statistically significant difference. Among stage II patients, no major differences in local recurrence were seen between the groups; the incidence of distant metastases tended to be high in the irradiated group. The incidence of both local recurrence and distant metastases for stage III patients showed a tendency to be higher in the irradiated group than in the non-irradiated group. The results indicated no apparent benifit of postoperative irradiation for breast cancer. A randomized clinical trial is needed for the evaluation of postoperative irradiation for breast cancer. (Namekawa, K.)

Comparison of Laparoscopic and Microscopic Subinguinal Varicocelectomy in terms of Postoperative Scrotal Pain

Science.gov (United States)

Penbegül, Necmettin; Atar, Murat; Bozkurt, Yaşar; Sancaktutar, Ahmet Ali; Altunoluk, Bülent

2012-01-01

Background and Objectives: In this study, 2 different varicocelectomy methods were compared with regard to postoperative scrotal pain, length of operation, and complications. Methods: Forty varicocele patients, who visited our clinic because of infertility or scrotal pain between 2008 and 2009, were enrolled in this clinical study. Microscopic subinguinal varicocelectomy was performed on 20 patients in Group I, and laparoscopic varicocelectomy was performed on 20 patients in Group II. Following surgery, the patients were assessed for postoperative requirements for analgesia; return to normal activity; varicocele recurrence; hydrocele formation; scrotal pain at postoperative days 1, 3, and 7; and other complications. Results: Mean age was 24.2±3.4 years in Group I and 25.1±2.1 years in Group II. Mean pain scores at postoperative 1, 3, and 7 days in Group I were (5.20±1.14, 4.60±0.97, and 3.50±0.97, respectively) significantly higher than those of Group II (0.70±0.82, 0.60±0.84, and 0.10±0.32, respectively). Time to return to normal activity was significantly shorter in Group II (3.7±2.1 days) compared with Group I (6.8±3.4 days) (p=0.028). However, the number of recurrences and hydroceles, as a complication of varicocelectomy, was 2 times higher in Group II (10%) than in Group I (5%). Conclusions: We believe that laparoscopic varicocelectomy is a safe, effective, and minimally invasive procedure. Furthermore, reduced postoperative discomfort and earlier return to normal activity are additional advantages of this method. PMID:23477168

Genital tuberculosis in a tamoxifen-treated postmenopausal woman with breast cancer and bloody vaginal discharge

Directory of Open Access Journals (Sweden)

Maraki Sofia

2006-09-01

Full Text Available Abstract Background Female genital tuberculosis is an uncommon disease that is rarely diagnosed in developed countries. Case presentation A 61-year-old postmenopausal woman who had undergone surgery and treated with adjuvant chemotherapy for infiltrating ductal carcinoma of the breast five years ago, presented with bloody vaginal discharge, fatigue, weight loss, and low grade fevers at night for two months. Histological examination of the endometrium, done based on the suspicion of a second primary cancer due to the tamoxifen therapy, revealed a granulomatous reaction. Liquid and solid mycobacterial cultures of the tissues were performed. Although the acid fast staining was negative, the liquid culture was positive for Mycobacterium tuberculosis. Involvement of other systems was not detected. The patient was treated with a three-drug antituberculosis regimen for 9 months and recovered fully. Conclusion Female genital tuberculosis is a rare but curable disease that should be included in the differential diagnosis of women with menstrual problems. Early diagnosis is important and may prevent unnecessary invasive procedures for the patient.

Predictors of Post-Operative Pain Relief in Patients with Chronic Pancreatitis Undergoing the Frey or Whipple Procedure.

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Sinha, Amitasha; Patel, Yuval A; Cruise, Michael; Matsukuma, Karen; Zaheer, Atif; Afghani, Elham; Yadav, Dhiraj; Makary, Martin A; Hirose, Kenzo; Andersen, Dana K; Singh, Vikesh K

2016-04-01

Post-operative pain relief in chronic pancreatitis (CP) is variable. Our objective was to determine clinical imaging or histopathologic predictor(s) of post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. All patients who underwent a Whipple (n = 30) or Frey procedure (n = 30) for painful CP between January 2003 and September 2013 were evaluated. A toxic etiology was defined as a history of alcohol use and/or smoking. The pre-operative abdominal CT was evaluated for calcification(s) and main pancreatic duct (MPD) dilation (≥5 mm). The post-operative histopathology was evaluated for severe fibrosis. Clinical imaging and histopathologic features were evaluated as predictors of post-operative pain relief using univariable and multivariable regression analysis. A total of 60 patients (age 51.6 years, 53% males) were included in our study, of whom 42 (70%) reported post-operative pain relief over a mean follow-up of 1.1 years. There were 37 (62%) patients with toxic etiology, 36 (60%) each with calcification(s) and MPD dilation. A toxic etiology, calcifications, and severe fibrosis were associated with post-operative pain relief on univariable analysis (all p Whipple or Frey procedure.

Facility-level association of preoperative stress testing and postoperative adverse cardiac events.

Science.gov (United States)

Valle, Javier A; Graham, Laura; Thiruvoipati, Thejasvi; Grunwald, Gary; Armstrong, Ehrin J; Maddox, Thomas M; Hawn, Mary T; Bradley, Steven M

2018-06-22

Despite limited indications, preoperative stress testing is often used prior to non-cardiac surgery. Patient-level analyses of stress testing and outcomes are limited by case mix and selection bias. Therefore, we sought to describe facility-level rates of preoperative stress testing for non-cardiac surgery, and to determine the association between facility-level preoperative stress testing and postoperative major adverse cardiac events (MACE). We identified patients undergoing non-cardiac surgery within 2 years of percutaneous coronary intervention in the Veterans Affairs (VA) Health Care System, from 2004 to 2011, facility-level rates of preoperative stress testing and postoperative MACE (death, myocardial infarction (MI) or revascularisation within 30 days). We determined risk-standardised facility-level rates of stress testing and postoperative MACE, and the relationship between facility-level preoperative stress testing and postoperative MACE. Among 29 937 patients undergoing non-cardiac surgery at 131 VA facilities, the median facility rate of preoperative stress testing was 13.2% (IQR 9.7%-15.9%; range 6.0%-21.5%), and 30-day postoperative MACE was 4.0% (IQR 2.4%-5.4%). After risk standardisation, the median facility-level rate of stress testing was 12.7% (IQR 8.4%-17.4%) and postoperative MACE was 3.8% (IQR 2.3%-5.6%). There was no correlation between risk-standardised stress testing and composite MACE at the facility level (r=0.022, p=0.81), or with individual outcomes of death, MI or revascularisation. In a national cohort of veterans undergoing non-cardiac surgery, we observed substantial variation in facility-level rates of preoperative stress testing. Facilities with higher rates of preoperative stress testing were not associated with better postoperative outcomes. These findings suggest an opportunity to reduce variation in preoperative stress testing without sacrificing patient outcomes. © Article author(s) (or their employer(s) unless otherwise

Causes and management of postoperative enterocutaneous fistulas

International Nuclear Information System (INIS)

Memon, A.S.; Siddiqui, F.G

2004-01-01

Objective: To identify the causes of postoperative enterocutaneous fistulas and to evaluate the results of conservative and operative treatment including the effectiveness of octreotide in the management of these fistulas. Subjects and Methods: Forty patients with postoperative fistula were studied. Demographic variables, causes and management outcome was observed and recorded. Results: There were 25 males and 15 females with 50% of the patients being in age group of 21-30 years. Emergency surgery for typhoid perforation(45%) and intestinal tuberculosis (30%) were the commonest causes. Ileum and jejunum were the commonest sites of fistulation found in 85% cases. Twenty-one patients were started on conservative treatment with spontaneous closure occurring in 15 (71.4%) patients. Nineteen patients were operated within three days of admission due to generalized peritonitis (73.7%) and local intra-abdominal collections (26.3%). Wound infection was the commonest complication in the operative group. The mortality rate in this series was 7.5%. All the deaths occurred following surgery. Conclusion: Postoperative enterocutaneous fistula has a high morbidity and a significant mortality. Sepsis in the peritoneal cavity is the major cause of mortality. Conservative treatment has a good outcome for these fistulas. The use of octreotide is highly recommended as it definitely converts high output fistulas to low output fistulas. (author)

Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

International Nuclear Information System (INIS)

King, Christopher R.; Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

2008-01-01

Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity ≤1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level ≤1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = ∼0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates

Study on effectiveness and tolerance of pre-and postoperative radiochemotherapy for patients with stomach cancer

International Nuclear Information System (INIS)

Wydmanski, J.

2008-01-01

Postoperative radiochemotherapy was included to the therapeutic scheme of stomach cancer. The effectiveness and tolerance of pre- and postoperative radiochemotherapy were studied. A Range Scale Risk reflecting the risk of treatment failure , selecting patients with bad prognosis to intensive therapy was established on the base of identified predictive and prognostic factors. 426 patients with stomach cancer were undergone radiochemotherapy between 1999 and 2005. The therapeutic schemes with operation followed by adjuvant radiochemotherapy or pre-and postoperative radiochemotherapy were arranged.The overall survival was better in the second group. Body weight loss, age and performance status of patients, location of tumor, cancer stage evaluation, resected lymph nodes, operation radicality were identified as the independent prognostic factors. In conclusions, combined modality approaches in treatment of stomach cancer were shown as more effective than surgery alone. Neoadjuvant chemotherapy may be more effective than postoperative one. Postoperative radiochemotherapy started and completed within 5 weeks positively influenced all prognostic factors. 5-year overall survival rate was 66% and risk of local recurrence less than 15%. 4 prognostics groups of patients selected in 10 points scale of range scale risk by careful evaluation using hazard model were established and detailed results have been presented. (author)

[Application of the xenogenic acellular dermal matrix membrane application used in the postoperative tissue shortage repair].

Science.gov (United States)

Bai, Yanxia; Yan, Liying; Zhang, Shaoqiang; Shao, Yuan; Yao, Xiaobao; Li, Honghui; Zhao, Ruimin; Zhao, Qian; Zhang, Pengfei; Yang, Qi

2014-09-01

To observe the short-term and long-term curative effect of the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer) application used in the 82 cases postoperative tissue shortage repair that after the head neck carcinoma resection. To held the 82 cases head neck carcinoma postoperative mucosa shortage repaired after resection by the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer), 65 cases mucosa shortage wound be directly covered by the repair membrane and the other 17 cases mucosa shortage wound be repaired by the tranfered muscle tissue flap with the repair membrane covered; 53 cases underwent additional postoperative radiotherapy between 2-4 weeks and follow-up in 1, 3, 6, 12, 18, 24, 30, 36, 48, 60 months and observed the operation site repair process through the electronic laryngoscope, observed the patients respiration, swallow, phonation function. Seventy-seven cases patients operation incision reached I phase healing standard, another 5 cases patients operation incision reached II phase healing standard because of the wound infection and fully-recovered through the local wound drainage,dressing process. All the patients tracheal cannula,the stomach tube be extubated successfully and without the local cicatricial constriction occurred. Seventy-eight cases follow up period reached 1 year including 53 cases who underwent postoperative radiotherapy, 49 cases follow up period reached 3 years including 32 cases who underwent postoperative radiotherapy, 14 cases follow up period reached 5 years including 12 cases who underwent postoperative radiotherapy. The patients with static local lesions discovered no reaction such as exclusion, allergy. The application of xenogenic acellular dermal matrix membrane (or joint muscle flap transfer used in in the postoperative tissue shortage repair that after the head neck carcinoma resection have several advantage such as comparatively easily implementation, operation safety

Bilateral postoperative maxillary cysts after orthognathic surgery: A case report

International Nuclear Information System (INIS)

Lee, Jung Hye; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul

2014-01-01

Postoperative maxillary cysts are locally aggressive lesions, usually developing as delayed complications many years after radical antral surgery. This report describes a case of bilateral postoperative maxillary cysts following orthognathic surgery performed approximately 21 years previously. The patient complained of stinging pain on her right cheek. Radiographic examination revealed low-attenuation lesions on both maxillary sinuses with discontinuously corticated margins without distinct expansion or bone destruction. The cysts were enucleated with the removal of metal plates and screws for pain relief. Histopathological examination confirmed the diagnosis of postoperative maxillary cysts lined by ciliated, pseudostratified columnar cells. The patient has remained asymptomatic thus far, and there was no evidence of local recurrence at 21 months of postoperative follow-up.

Bilateral postoperative maxillary cysts after orthognathic surgery: A case report

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Lee, Jung Hye; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Dept. of Oral and Maxillofacial Radiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of)

2014-12-15

Postoperative maxillary cysts are locally aggressive lesions, usually developing as delayed complications many years after radical antral surgery. This report describes a case of bilateral postoperative maxillary cysts following orthognathic surgery performed approximately 21 years previously. The patient complained of stinging pain on her right cheek. Radiographic examination revealed low-attenuation lesions on both maxillary sinuses with discontinuously corticated margins without distinct expansion or bone destruction. The cysts were enucleated with the removal of metal plates and screws for pain relief. Histopathological examination confirmed the diagnosis of postoperative maxillary cysts lined by ciliated, pseudostratified columnar cells. The patient has remained asymptomatic thus far, and there was no evidence of local recurrence at 21 months of postoperative follow-up.

National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial: advancing the science of recruitment and breast cancer risk assessment in minority communities.

Science.gov (United States)

McCaskill-Stevens, Worta; Wilson, John W; Cook, Elise D; Edwards, Cora L; Gibson, Regina V; McElwain, Diane L; Figueroa-Moseley, Colmar D; Paskett, Electra D; Roberson, Noma L; Wickerham, D Lawrence; Wolmark, Norman

2013-04-01

One of the first chemoprevention trials conducted in the western hemisphere, the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women. The purpose of this report is to review various patient recruitment efforts the NSABP developed to enhance the participation of racial and ethnic minority women in the Study of Tamoxifen and Raloxifene (STAR) trial and to describe the role that the recruitment process played in the implementation and understanding of breast cancer risk assessment in minority communities. The NSABP STAR trial was a randomized, double-blinded study comparing the use of tamoxifen 20 mg/day to raloxifene 60 mg/day, for a 5-year period, to reduce the risk of developing invasive breast cancer. Eligible postmenopausal women were required to have a 5-year predicted breast cancer risk of 1.66% based on the modified Gail Model. For the current report, eligibility and enrollment data were tabulated by race/ethnicity for women who submitted STAR risk assessment forms (RAFs). A total of 184,460 RAFs were received, 145,550 (78.9%) from white women and 38,910 (21.1%) from minority women. Of the latter group, 21,444 (11.6%) were from African Americans/blacks, 7913 (4.5%) from Hispanics/Latinas, and 9553 (5.2%) from other racial or ethnic groups. The percentages of risk-eligible women among African Americans, Hispanics/Latinas, others, and whites were 14.2%, 23.3%, 13.7%, and 57.4%, respectively. Programs targeting minority enrollment submitted large numbers of RAFs, but the eligibility rates of the women referred from those groups tended to be lower than the rates among women referred outside of those programs. The average number of completed risk assessments increased among minority women over the course of the recruitment period compared to those from whites. We have not

Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

Science.gov (United States)

Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

2015-12-01

For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can

Reducing Postoperative Pain from Tonsillectomy Using Monopolar Electrocautery by Cooling the Oropharynx

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Vieira, Lucas

2014-01-01

Full Text Available Objective Evaluate intraoperative cooling of the oropharynx to reduce postoperative pain in tonsillectomy using monopolar electrocautery. Methods Sixty-six patients, age 1 to 12 years, were selected for the study, 33 in the control group and 33 in the experimental group. After randomization, patients underwent subcapsular dissection and hemostasis with monopolar electrocautery. Patients in the experimental group had the oropharynx cooled after tonsil dissection and hemostasis for 10 minutes. The procedure was done through the oral cavity by irrigation with 500 mL of 0.9% saline, in temperatures between 5°C and 10°C, for 5 minutes. The evaluation of postoperative pain was made with the pain visual analog scale (VAS for 10 days. As complementary data on the evaluation of pain, we recorded daily use of ketoprofen for pain relief. Results Pain after tonsillectomy assessed by VAS was significantly lower in the experimental group at days 0, 5, and 6 (p < 0.05. There were no differences in the use of ketoprofen between the groups. Conclusion Cooling of the oropharynx after tonsillectomy promotes clinically significant reduction in postoperative pain, without additional complications.

Efficacy of postoperative prophylactic antibiotics in reducing permanent pacemaker infections.

Science.gov (United States)

Lee, Wen-Huang; Huang, Ting-Chun; Lin, Li-Jen; Lee, Po-Tseng; Lin, Chih-Chan; Lee, Cheng-Han; Chao, Ting-Hsing; Li, Yi-Heng; Chen, Ju-Yi

2017-08-01

Despite limited evidence, postoperative prophylactic antibiotics are often used in the setting of permanent pacemaker implantation or replacement. The aim of this study is to investigate the efficacy of postoperative antibiotics. Postoperative prophylactic antibiotics may be not clinically useful. We recruited 367 consecutive patients undergoing permanent pacemaker implantation or generator replacement at a tertiary referral center. Baseline demographics, clinical characteristics, and procedure information were collected, and all patients received preoperative prophylactic antibiotics. Postoperative prophylactic antibiotics were administered at the discretion of the treating physician, and all patients were seen in follow-up every 3 to 6 months for an average follow-up period of 16 months. The primary endpoint was device-related infection. A total of 110 patients were treated with preoperative antibiotics only (group 1), whereas 257 patients received both preoperative and postoperative antibiotics (group 2). After a mean follow-up period of 16 months, 1 patient in group 1 (0.9%) and 4 patients in group 2 (1.5%) experienced a device-related infection. There was no significant difference in the rate of infection between the 2 groups (P = 0.624). In the univariate analysis, only the age (60 ± 11 vs 75 ± 12 years, P antibiotics had a similar rate of infection as those treated with preoperative antibiotics alone. Further studies are needed to confirm these preliminary findings. © 2017 Wiley Periodicals, Inc.

Pre- and post-operative evaluation of ventricular function, muscle mass and valve morphology by MR tomography in Ebstein's anomaly

International Nuclear Information System (INIS)

Gutberlet, M.; Oellinger, H.; Amthauer, H.; Hoffmann, T.; Felix, R.; Ewert, P.; Nagdyman, N.; Lange, P.; Hetzer, R.

2000-01-01

Purpose: To evaluate the value of MRT with spin echo (SE) and CINE gradient echo (GE) sequences for the pre- and postoperative assessment of patients with Ebstein's anomaly. Methods: Twelve patients within the ages of four to 49 years (mean 22±12 years) were examined pre- (n=5) or postoperatively (n=7) after tricuspid valve reconstruction with a 1.5 T scanner. For the anatomical assessment, an ECG-gated transverse SE-sequence, for the assessment of valve morphology and function as well as for volumetry a CINE GE-sequence with retrospective gating was used. With the use of the multislice-multiphase technique, after summing up the manually outlined epi- and endocardial areas, endsystolic (ESV) and enddiastolic volumes (EDV), ejection fraction (EF), stroke volume (SV), and muscle mass (MM) were calculated for both ventricles. Results: The differentiation of the displaced parts of the tricuspid valve (TV) was insufficient with static SE, but was possible in all patients with CINE-MRT. Like in Doppler echocardiography, a qualitative assessment of tricuspid insufficiency was possible in CINE-MRT, the mean incompetence grade preoperative was 1.8 (±0.8), postoperative 0.7 (±0.5). The mean RV-EF in the preoperative group was 41.8% (±6.4), in the postoperative group 47.9% (±10.6), the mean LV-EF preoperative 47.4% (±8.5%), postoperative 63,0% (±9.4). Conclusion: CINE-MRT should rather be used than SE for the assessment of valve morphology. EF, muscle mass and tricuspid incompetence can also be calculated pre- and postoperative with CINE-MRT. (orig.) [de

Aspheric photorefractive keratectomy for myopia and myopic astigmatism with the SCHWIND AMARIS laser: 2 years postoperative outcomes

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Aslanides, Ioannis M.; Padroni, Sara; Arba-Mosquera, Samuel

2012-01-01

Purpose To evaluate mid-term refractive outcomes and higher order aberrations of aspheric PRK for low, moderate and high myopia and myopic astigmatism with the AMARIS excimer laser system (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). Methods This prospective longitudinal study evaluated 80 eyes of 40 subjects who underwent aspheric PRK. Manifest refractive spherical equivalent (MRSE) of up to −10.00 diopters (D) at the spectacle plane with cylinder up to 3.25 was treated. Refractive outcomes and corneal wavefront data (6 mm pupil to the 7th Zernike order) were evaluated out to 2 years postoperatively. Statistical significance was indicated by P  0.05, both cases). There was a statistical increase in postoperative coma (+0.12 μm) and spherical aberration (+0.14 μm) compared to preoperatively (P < 0.001, both cases). Conclusion Aspheric PRK provides excellent visual and refractive outcomes with induction in individual corneal aberrations but not overall corneal aberrations.

Levonorgestrel Intrauterine Device Placement in a Premenopausal Breast Cancer Patient with a Bicornuate Uterus.

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Eskew, Ashley M; Crane, Erin K

2016-01-01

Young women with breast cancer face contraceptive challenges. Data are limited and conflicting on the use of the levonorgestrel intrauterine device (LNG-IUD) in this patient population. A 32-year-old nulligravid woman with a history of breast cancer on tamoxifen presented with new-onset vaginal bleeding. Further workup revealed a previously undiagnosed bicornuate uterus. She underwent hysteroscopy, dilation and curettage, and LNG-IUD placement in each uterine horn. Postoperative follow-up confirmed retention and proper placement of both IUDs. Pathology from the dilation and curettage was benign, and the abnormal uterine bleeding abated. LNG-IUD placement in a young patient with a personal history of breast cancer on tamoxifen and a bicornuate uterus is a safe and feasible alternative for contraception. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Safety and efficacy of immediate postoperative feeding and bowel stimulation to prevent ileus after major gynecologic surgical procedures.

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Fanning, James; Hojat, Rod

2011-08-01

Postoperative ileus is a major complication of abdominal surgical procedures To evaluate the incidence of ileus and gastrointestinal morbidity in patients who received immediate postoperative feeding and bowel stimulation after undergoing major gynecologic surgical procedures. During a 5-year period, the authors tracked demographic, surgical outcome, and follow-up information for 707 patients who underwent major gynecologic operations. All patients received the same postoperative orders, including immediate feeding of a diet of choice and bowel stimulation with 30 mL of magnesium hydroxide (milk of magnesia) twice daily until bowel movements occurred. Of 707 patients, 6 (<1%) had postoperative ileus. No patients experienced postoperative bowel obstruction and 2 patients (0.3%) had postoperative intestinal leak. No serious adverse effects associated with bowel stimulation were reported. Immediate postoperative feeding and bowel stimulation is a safe and effective approach to preventing ileus in patients who undergo major gynecologic surgical procedures.

Estrogen receptor testing and 10-year mortality from breast cancer: A model for determining testing strategy

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Christopher Naugler

2012-01-01

Full Text Available Background: The use of adjuvant tamoxifen therapy in the treatment of estrogen receptor (ER expressing breast carcinomas represents a major advance in personalized cancer treatment. Because there is no benefit (and indeed there is increased morbidity and mortality associated with the use of tamoxifen therapy in ER-negative breast cancer, its use is restricted to women with ER expressing cancers. However, correctly classifying cancers as ER positive or negative has been challenging given the high reported false negative test rates for ER expression in surgical specimens. In this paper I model practice recommendations using published information from clinical trials to address the question of whether there is a false negative test rate above which it is more efficacious to forgo ER testing and instead treat all patients with tamoxifen regardless of ER test results. Methods: I used data from randomized clinical trials to model two different hypothetical treatment strategies: (1 the current strategy of treating only ER positive women with tamoxifen and (2 an alternative strategy where all women are treated with tamoxifen regardless of ER test results. The variables used in the model are literature-derived survival rates of the different combinations of ER positivity and treatment with tamoxifen, varying true ER positivity rates and varying false negative ER testing rates. The outcome variable was hypothetical 10-year survival. Results: The model predicted that there will be a range of true ER rates and false negative test rates above which it would be more efficacious to treat all women with breast cancer with tamoxifen and forgo ER testing. This situation occurred with high true positive ER rates and false negative ER test rates in the range of 20-30%. Conclusions: It is hoped that this model will provide an example of the potential importance of diagnostic error on clinical outcomes and furthermore will give an example of how the effect of that

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

DEFF Research Database (Denmark)

Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S

2016-01-01

PURPOSE: To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. METHODS: The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor......-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards......). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age...

Postoperative CT findings of aortic aneurysm and dissection

International Nuclear Information System (INIS)

Seong, Su Ok; Lee, Ghi Jai; Kim, Mi Young; Moon, Hi Eun; Shim, Jae Chan; Lee, Hong Sup; Kim, Ho Kyun; Han, Chang Yul

1995-01-01

To assess the postoperative CT findings of aortic aneurysms or dissections treared by resection-and graft replacement or continuous-suture graft-inclusion technique. We reviewed postoperative follow-up CT findings of 14 patients, 19 cases. There were 8 patients (10 cases) of aortic aneurysm and 6 patients (9 cases) of aortic dissection which involved the thoracic aorta in 9 patients (13 cases) and abdominal aorta in 5 patients (6 cases). The interval of follow-up after operation was from 9 days to 2 year 9 months. On CT scans, we analyzed the appearance of graft materials, differences of CT findings between two surgical techniques, and normal or abnormal postoperative CT findings. Most of grafts appeared as hyperdense ring on precontrast scan, and all of them were not separated from aortic lumen on postcontrast scan. On CT findings of patients who were operated by continuous-suture graft-inclusion technique, perigraft thrombus was concentrically located with sharp demarcation by native aortic wall and its density was homogeneous, but in cases of those operated by resection-and graft replacement, perigraft hematoma was eccentrically located with indistinct margin and its density was heterogeneous and native aortic wall could not be delineated. In patients without complication, perigraft thrombus or hematoma (15 cases), perigraft calcification (11 cases), residual intimal flap (6 cases), graft deformity (4 cases), perigraft air (2 cases) and reconstructed vessels (1 cases) were noted. And in one patient with complication, perigraft flow was noted with more increased perigraft hematoma. Precise knowledge of the differences of CT findings between two surgical techniques and normal postoperative CT findings is crucial to evaluated the postoperative CT findings in aortic aneurysm and dissection

Retrospective analysis of treatment outcomes after postoperative chemoradiotherapy in advanced gastric cancer

International Nuclear Information System (INIS)

Kim, Sup; Kim, Jun Sang; Jeong, Hyun Yong; Noh, Seung Moo; Kim, Ki Whan; Cho, Moon June

2011-01-01

To evaluate retrospectively the survival outcome, patterns of failure, and complications in patients treated with postoperative chemoradiotherapy (CRT) in advanced gastric cancer. Between January 2000 and December 2006, 80 patients with advanced gastric cancer who received postoperative concurrent CRT were included. Pathological staging was IB-II in 9%, IIIA in 38%, IIIB in 33%, and IV in 21%. Radiotherapy consisted of 45 Gy of radiation. Concurrent chemotherapy consisted of a continuous intravenous infusion of 5-fluorouracil and leucovorin on the first 4 days and last 3 days of radiotherapy. The median follow-up period was 48 months (range, 3 to 83 months). The 5-year overall survival, disease-free survival, and locoregional recurrence-free survivals were 62%, 59%, and 80%, respectively. In the multivariate analysis, significant factors for disease-free survival were T stage (hazard ratio [HR], 0.278; p = 0.038), lymph node dissection extent (HR, 0.201; p = 0.002), and maintenance oral chemotherapy (HR, 2.964; p = 0.004). Locoregional recurrence and distant metastasis occurred in 5 (6%) and 18 (23%) patients, respectively. Mixed failure occurred in 10 (16%) patients. Grade 3 leukopenia and thrombocytopenia were observed in 4 (5%) and one (1%) patient, respectively. Grade 3 nausea and vomiting developed in 8 (10%) patients. Intestinal obstruction developed in one (1%). The survival outcome of the postoperative CRT in advanced gastric cancer was similar to those reported previously. Our postoperative CRT regimen seems to be a safe and effective method, reducing locoregional failure without severe treatment toxicity in advanced gastric cancer patients.

Postoperative radiation therapy after hip replacement in high-risk patients for development of heterotopic bone formation

International Nuclear Information System (INIS)

Hashem, R.; Rene, N.; Souhami, L.; Tanzer, M.; Evans, M.

2011-01-01

Purpose. - To report the results of postoperative radiation therapy in preventing the development of heterotopic bone formation after hip replacement surgery in high-risk patients. Patients and methods. - Between 1991 and 2007, 44 patients were preventively treated with postoperative RT after total hip replacement. In total, 47 hips were treated. All patients were considered at high risk for developing heterotopic bone formation. Most patients (63.5%) were treated because of a history of severe osteoarthritis or ankylosing spondylitis. All patients were treated with shaped parallel-opposed fields with a single fraction of 7 Gy using 6 or 18 MV photons. Most patients (94%) received radiation therapy within 72 hours postoperative and in only three patients radiation therapy was delivered after 72 hours post-surgery (5-8 days). Results. - Minimum follow-up was 1 year. There were 18 females and 26 males. Median age was 63 years (range: 18-80). Treatments were well tolerated and no acute toxicity was seen post-radiation therapy. Only one of the 47 hips (2%) developed heterotopic bone formation. This patient received postoperative radiation therapy to both hips but only developed heterotopic bone formation in one of them. None of the three patients treated beyond 72 hours failed. To date no late toxicity has been observed. Conclusion. - The use of postoperative radiation therapy was an effective and safe treatment in the prevention of heterotopic bone formation in a high-risk group of patients undergoing total hip replacement. (authors)

Iodine-125-labelled tamoxifen is differentially cytoxic to cells containing oestrogen receptors

International Nuclear Information System (INIS)

Bloomer, W.D.; McLaughlin, W.H.; Weichselbaum, R.R.

1980-01-01

Tamoxifen, a non-steroidal anti-oestrogen competes with 17 - oestradiol for oestrogen receptor protein and is translocated to the nucleus. Carrier-free 125 I-TAM was tested for cytotoxicity in oestrogen receptor rich (human breast cancer MCF-7) and poor (V-79 Chinese hamster) cells. 125 I-TAM was differentially cytotoxic to MCF-7 cells. The D 37 values for MCF-7 and V-79 cells were 0.5 and 1.5 pCi/cell respectively. No radiotoxicity was observed with Na 125 I at doses equal to 125 I-TAM; iodide was effectively excluded from both cell lines and remained in the extracellular space. Also, nonradioactive 127 I-TAM and TAM were both non-toxic when tested at levels comparable to 125 I-TAM. It is suggested that the marked cytotoxicity in MCF-7 cells results from close approximation of 125 I with the genetic apparatus as a result of direct charging of specific nuclear receptors and/or translocation of 125 I-TAM receptor complexes from the cytoplasm to the nucleus, and that the minimal toxicity in V-79 cells reflects transmitted cytoplasmic radiation effects, limited direct nuclear charging and/or limited nuclear translocation resulting from the relative paucity of oestrogen in the cells. (U.K.)

Postoperative craniospinal radiotherapy of medulloblastoma in children and young adults

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Golubičić Ivana V.

2003-01-01

Full Text Available PURPOSE The aim of this study was: 1. to evaluate treatment results of combined therapy (surgery, postoperative craniospinal radiotherapy with or without chemotherapy and 2. to assess factors affecting prognosis (extend of tumor removal, involvement of the brain stem, extent of disease postoperative meningitis, shunt placement, age, sex and time interval from surgery to start of postoperative radiotherapy. PATIENTS AND METHODS During the period 1986-1996, 78 patients with medulloblastoma, aged 1-22 years (median 8.6 years, were treated with combined modality therapy and 72 of them were evaluable for the study end-points. Entry criteria were histologically proven diagnosis, age under 22 years, and no history of previous malignant disease. The main characteristics of the group are shown in Table 1. Twenty-nine patients (37.2% have total, 8 (10.3% near total and 41 (52.5% partial removal. Seventy-two of 78 patients were treated with curative intent and received postoperative craniospinal irradiation. Radiotherapy started 13-285 days after surgery (median 36 days. Only 13 patients started radiotherapy after 60 days following surgery. Adjuvant chemotherapy was applied in 63 (80.7% patients. The majority of them (46 73% received chemotherapy with CCNU and Vincristine. The survival rates were calculated with the Kaplan-Meier method and the differences in survival were analyzed using the Wilcoxon test and log-rank test. RESULTS The follow-up period ranged from 1-12 years (median 3 years. Five-year overall survival (OS was 51% and disease-free survival (DFS 47% (Graph 1. During follow-up 32 relapses occurred. Patients having no brain stem infiltration had significantly better survival (p=0.0023 (Graph 2. Patients with positive myelographic findings had significantly poorer survival compared to dose with negative myelographic findings (p=0.0116. Significantly poorer survival was found in patients with meningitis developing in the postoperative period

Ankylosing Spondylitis Increases Perioperative and Postoperative Complications After Total Hip Arthroplasty.

Science.gov (United States)

Blizzard, Daniel J; Penrose, Colin T; Sheets, Charles Z; Seyler, Thorsten M; Bolognesi, Michael P; Brown, Christopher R

2017-08-01

Ankylosing spondylitis (AS) is a chronic autoimmune spondyloarthropathy that primarily affects the axial spine and hips. Progressive disease leads to pronounced spinal kyphosis, positive sagittal balance, and altered biomechanics. The purpose of this study is to determine the complication profile of patients with AS undergoing total hip arthroplasty (THA). The Medicare sample was searched from 2005 to 2012 yielding 1006 patients with AS who subsequently underwent THA. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for 90-day, 2-year, and the final postoperative follow-up for complications including hip dislocation, periprosthetic fracture, wound complication, revision THA, and postoperative infection. Compared to controls, AS patients had an RR of 2.50 (CI, 1.04-5.99) of THA component breakage at 90-days post-operatively and 1.99 (CI, 1.10-3.59) at 2-years. The RR of periprosthetic hip dislocation was elevated at 90 days (1.44; CI, 0.93-2.22) and significantly increased at 2-years (1.67; CI, 1.25-2.23) and overall follow-up (1.49; CI, 1.14-1.93). Similarly, the RR for THA revision was elevated at 90-days (1.46; CI, 0.97-2.18) and significantly increased at 2-years (1.69; CI, 1.33-2.14) and overall follow-up (1.51; CI, 1.23-1.85). Patients with AS are at increased risk for complications after THA. Altered biomechanics from a rigid, kyphotic spine place increased demand on the hip joints. The elevated perioperative and postoperative risks should be discussed preoperatively, and these patients may require increased preoperative medical optimization as well as possible changes in component selection and position to compensate for altered spinopelvic biomechanics. Copyright © 2017 Elsevier Inc. All rights reserved.

Osteosarcoma in the anterior chest wall that developed 20 years after postoperative radiotherapy for breast cancer

International Nuclear Information System (INIS)

Murata, Mariko; Shoji, Tsuyoshi; Nakayama, Ei; Bando, Toru

2008-01-01

Sarcomas are a rare complication of radiotherapy for breast cancer and such patients have a poor prognosis. We report resection of an osteosarcoma in the chest wall that developed 20 years after postoperative radiotherapy for breast cancer. A 57-year-old woman was referred to our department for examination and treatment of an anterior chest wall tumor in April 2007. In September 1986, she had undergone a radical mastectomy and postoperative irradiation and chemotherapy for right breast cancer. In December 2003, she underwent chemotherapy for recurrence of breast cancer which was pointed out on computed tomography involving the pleura and left superior clavicular lymph nodes. In March 2006, follow-up computed tomography of the chest demonstrated the destruction of the sternum, which was diagnosed as recurrence and she was followed with chemotherapy for breast cancer continuously thereafter. In April 2007, because of the developing sternal tumor, excisional biopsy was performed and histopathology indicated sarcoma. In May 2007, resection of the chest wall tumor with the sternum, bilateral clavicles, bilateral first and second ribs, and right partial lung (upper and middle lobe) were performed, and the chest wall defect was reconstructed with a rectus abdominis musculocutaneous free flap. Histopathologically, the tumor was osteosarcoma with margin free. Adjuvant radiotherapy to the breast plays a significant role in preventing local disease recurrence in women treated for breast cancer. However, radiotherapy can induce malignant sarcoma after a latency period of several years. The risk is extremely low for the individual patient, but this disease is aggressive and associated with a poor overall prognosis. Therefore, early detection is necessary for optimal treatment and incisional biopsy is necessary for accurate diagnosis. (author)

Comparison of 2% chlorhexidine and 5.25% sodium hypochlorite irrigating solutions on postoperative pain: A randomized clinical trial

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Bashetty Kusum

2010-01-01

Full Text Available Aim: To compare the levels of postoperative pain after cleaning and shaping of root canals using two different root canal irrigants for debridement. Materials and Methods: Forty patients with irreversible pulpitis, pulp necrosis and non-vital teeth exhibiting acute apical periodontitis requiring root canal treatment were included. At random, canals were cleaned and shaped with the following protocols. 2% chlorhexidine solution in group I and 5.25% sodium hypochlorite solution in group II were used as an irrigants. Access cavities were closed with a sterile cotton pellet and cavit. The patients recorded degree of pain at various time intervals after cleaning and shaping on a visual analogue scale for 1 week. Results: The mean pain score for group I was between 0.65 and 3.35 and for group II was between 0.95 and 4.50. There was significant difference in the pain level between the two groups only at 6 th hour postoperatively (P<0.05 and the pain was more in sodium hypochlorite group. Conclusions: More pain was present in teeth irrigated using 5.25% sodium hypochlorite when compared to that in teeth irrigated using 2% chlorhexidine solution. Significant difference in pain level was present only at 6th hour postoperatively, and at all other periods (24 th hour, 4 th and 7 th days there was no significant difference in pain level between the two groups.

Postoperative spinal column; Postoperative Wirbelsaeule

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Kaefer, W. [Westpfalzklinikum GmbH, Standort II, Abteilung fuer Wirbelsaeulenchirurgie, Kusel (Germany); Heumueller, I. [Westpfalzklinikum GmbH, Standort II, Institut fuer Radiologie II, Kusel (Germany); Harsch, N.; Kraus, C.; Reith, W. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

2016-08-15

As a rule, postoperative imaging is carried out after spinal interventions to document the exact position of the implant material. Imaging is absolutely necessary when new clinical symptoms occur postoperatively. In this case a rebleeding or an incorrect implant position abutting a root or the spinal cord must be proven. In addition to these immediately occurring postoperative clinical symptoms, there are a number of complications that can occur several days, weeks or even months later. These include the failed back surgery syndrome, implant loosening or breakage of the material and relapse of a disc herniation and spondylodiscitis. In addition to knowledge of the original clinical symptoms, it is also important to know the operation details, such as the access route and the material used. In almost all postoperative cases, imaging with contrast medium administration and corresponding correction of artefacts by the implant material, such as the dual energy technique, correction algorithms and the use of special magnetic resonance (MR) sequences are necessary. In order to correctly assess the postoperative imaging, knowledge of the surgical procedure and the previous clinical symptoms are mandatory besides special computed tomography (CT) techniques and MR sequences. (orig.) [German] In der Regel erfolgt bei spinalen Eingriffen eine postoperative Bildgebung, um die exakte Lage des Implantatmaterials zu dokumentieren. Unbedingt notwendig ist die Bildgebung, wenn postoperativ neue klinische Symptome aufgetreten sind. Hier muessen eine Nachblutung bzw. inkorrekte, eine Wurzel oder das Myelon tangierende Implantatlage nachgewiesen werden. Neben diesen direkt postoperativ auftretenden klinischen Symptomen gibt es eine Reihe von Komplikationen, die erst nach mehreren Tagen, Wochen oder sogar nach Monaten auftreten koennen. Hierzu zaehlen das Failed-back-surgery-Syndrom, die Implantatlockerung oder -bruch, aber auch ein Rezidivvorfall und die Spondylodiszitis. Neben der

[A Case of Noninvasive Ductal Carcinoma of the Breast in a Male].

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Yamashita, Yamato; Ishiba, Toshiyuki; Oda, Goshi; Nakagawa, Tsuyoshi; Aburatani, Tomoki; Ogo, Taiichi; Nakashima, Yutaka; Baba, Hironobu; Hoshino, Naoaki; Nishioka, Yoshinobu; Kawano, Tatsuyuki; Itoh, Takashi; Kirimura, Susumu; Kobayashi, Hirotoshi

2017-11-01

Breast cancer in male is rare, accounting for 1%of all breast cancers.Among male breast cancers, noninvasive carcinoma is extremely rare.We experienced a case of noninvasive carcinoma of the breast in a male.A 72-year-old male was referred to our hospital with a chief complaint of the tumor and blood secretion from the left nipple.Mammography revealed a highdensity mass.Ultrasound examination revealed low echoic mass at the E area, and it measured 1.5 cm.Core needle biopsy failed to provide a definitive diagnosis, and we performed an excisional biopsy of the tumor.The pathological diagnosis was noninvasive ductal carcinoma.He underwent a mastectomy without sentinel lymph node biopsy because the resection margin was positive.The patient received no adjuvant therapy and the patient's postoperative course was uneventful for 1 year.As there have been few reports on male noninvasive ductal carcinoma, we do not have evidence for indication of the sentinel lymph nodes and postoperative adjuvant therapy such as tamoxifen.We may confuse the treatment policy.

Postoperative Conversion Disorder in Elderly Oral Cancer Patient.

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Yakushiji, Takashi; Hayashi, Kamichika; Morikawa, Takamichi; Migita, Masashi; Ogane, Satoru; Muramatsu, Kyotaro; Kamio, Takashi; Shibahara, Takahiko; Takano, Nobuo

2016-01-01

Conversion disorder is a condition in which psychological stress in response to difficult situations manifests as physical symptoms. Here, we report a case of postoperative coma due to conversion disorder in an elderly oral cancer patient. An 82-year-old woman was referred to Tokyo Dental College Chiba Hospital with a mass lesion on the tongue. A biopsy revealed a well-differentiated squamous cell carcinoma. Surgical treatment was performed for the tongue carcinoma and tracheotomy for management of the airway. On postoperative day 5, the patient exhibited loss of consciousness (Glasgow Coma Scale: E1, VT, M1; Japan Coma Scale: III-300). The patient's vital signs were all normal, as were the results of a full blood count, brain-CT, MRI, and MRA. Only the arm dropping test was positive. Therefore, the cause of the coma was diagnosed as conversion disorder. Seven hours later, the patient showed a complete recovery.

Postoperative Respiratory Function and Survival After Pneumonectomy in Dogs and Cats.

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Majeski, Stephanie A; Steffey, Michele A; Mayhew, Philipp D; Hunt, Geraldine B; Holt, David E; Runge, Jeffrey J; Kass, Philip H; Mellema, Matthew

2016-08-01

To describe indications for, and outcomes after, pneumonectomy in dogs and cats, including assessment of immediate postoperative respiratory function in comparison to dogs undergoing single lung lobectomy. Retrospective case series. Dogs (n=16) and cats (n=7) with naturally occurring pulmonary disease. Medical records (1990-2014) of dogs and cats undergoing right or left pneumonectomy were reviewed. Data retrieved included signalment, history, preoperative diagnostics, operative descriptions, postoperative data including respiratory function, and postdischarge outcomes. For respiratory function comparisons, medical records of dogs having undergone a single lung lobectomy via median sternotomy (n=15) or intercostal thoracotomy (n=15) were reviewed. Twenty-three cases (16 dogs, 7 cats) were included. Pneumonectomy was performed for congenital (1 dog, 1 cat), neoplastic (8 dogs, 1 cat), and infectious (7 dogs, 5 cats) disease. Postoperative aspiration pneumonia occurred in 2 dogs; 15 of 16 dogs (94%) and 6/7 cats (86%) survived to hospital discharge. After pneumonectomy, dogs had a significantly higher postoperative PaO2 on 21% oxygen (P=.033) and lower postoperative A-a gradient (P=.004) compared to dogs undergoing single lung lobectomy. Survival times (right-censored at last follow-up) for dogs ranged from 2 days to 7 years (estimated median=1,868 days) and for cats from 1-585 days. Dogs and cats have acceptable respiratory function immediately postoperatively and most have protracted long-term survival after pneumonectomy for a variety of pulmonary diseases. © Copyright 2016 by The American College of Veterinary Surgeons.

Postoperative radiotherapy of supratentorial anaplastic gliomas

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Wendt, T.G.; Bacherler, B.; Baumer, K.; Rohloff, R.; Willich, N.

1986-01-01

Between 1970 and 1983, 149 patients with high grade anaplastic supratentorial gliomas received a postoperative irradiation during primary treatment. 118 out of these patients had an anaplastic astrocytoma, 18 an anaplastic oligodendroglioma, and 13 an anaplastic ependymoma. Most of these patients were treated by irradiation of a great volume with 50 Gy within five weeks, the others by irradiation of the total brain with 50 Gy within five weeks and saturation with 10 Gy within one week. The one-year survival of the total group was 35.5% and the two-year survival 10.6%. Patients at an age of less than 40 years show a significantly longer survival than older patients (one-year survival rates 40% and 30.7%, respectively). Patients suffering from anaplastic tumors with astrocytic and oligodendrocytic differentiation have a comparable prognosis. Patients suffering from anaplastic tumors with ependymal differentiation, however, have prolonged survival times. The therapy results of different treatment methods are discussed using the communications of literature. (orig.) [de

COMPARATIVE STUDY OF NALBUPHINE VS. PENTAZOCINE FOR POSTOPERATIVE ANALGESIA

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Naresh Ganpatrao Tirpude

2016-10-01

Full Text Available BACKGROUND To provide postoperative pain relief is a prime duty of health care providers. Failure to relieve pain is morally and ethically unacceptable. Post-operative pain may results in adverse effects such as: a Physiological Changes: Reduced pulmonary functions, e.g. vital capacity, tidal volume, functional residual capacity; sympathetic stimulation; reduced the physical activity of patients; thereby increasing the risk of venous thrombosis. b Psychological disturbances: Anger, Resentment, Depression, Adversarial Relationship with Doctors, Insomnia. Aim of this study was 1. To investigate whether “Postoperative analgesia with Nalbuphine is longer than Pentazocine”. 2. To investigate whether “Side effects/complications are less with Nalbuphine as compared to Pentazocine”. MATERIALS AND METHODS It was a prospective randomized double blind observational study. Eighty patients of hydrocoele & inguinal hernia were operated under spinal anaesthesia of age group 20-70 years, ASA grade I & II & patients with controlled co-morbid conditions. In postoperative period, Group N- Inj. Nalbuphine (0.3 mg/kg IM or Group P- Inj. Pentazocine (0.5 mg/kg IM was administered to provide postoperative pain relief & to know the duration of pain relief & its side effects. RESULTS On statistical analysis, demographic data i.e. age, sex had no influence on outcome of study. Mean VAS score in group N was highly significant (p-value in Inj. Pentazocine group. 2. Side Effects - Incidence of sedation was more in Nalbuphine group as compared to Pentazocine group. Nausea & Vomiting were more so in Pentazocine group as compared to Nalbuphine group. Limitation of the present study was that sample size was very small.

Three-year postoperative outcomes between MIS and conventional TLIF in1-segment lumbar disc herniation.

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Lv, You; Chen, Jingyang; Chen, Jinchuan; Wu, Yuling; Chen, Xiangyang; Liu, Yi; Chu, Zhaoming; Sheng, Luxin; Qin, Rujie; Chen, Ming

2017-06-01

The aim of this study is to assess the long-term clinical and radiological outcomes between minimally invasive (MIS) and conventional transforaminal lumbar interbody fusion (TLIF) in treating one-segment lumbar disc herniation (LDH). One-hundred and six patients treated by MIS-TLIF (50 cases) or conventional TLIF (56 cases) were included. Perioperative results were evaluated. Clinical outcomes were compared preoperatively and postoperatively. Radiologic parameters were based on a comparison of preoperative and three-year postoperative lumbar lordosis, segmental lordosis, sacral slope, the cross-sectional area of the paraspinal muscle and fusion rates. MIS TILF had significantly less blood, shorter operation time, mean return to work time and lower intramuscular pressure compared with the conventional group during the operation. VAS scores for lower back pain and ODI in MIS-TLIF were significantly decreased. The mean cross-sectional area of the paraspinal muscle was significantly decreased after surgery in the conventional TLIF group and no significant intragroup differences were established in the MIS-TLIF group. No significant differences were found in fusion rate, lumbar lordosis, segmental lordosis and sacral slope. Both MIS and conventional TLIF were beneficial for patients with LDH. However, MIS-TLIF manifests a great improvement in perioperative outcomes, low back pain, disability and preventing paraspinal muscle atrophy during the follow-up period observation.

Cleft maxillary distraction versus orthognathic surgery--which one is more stable in 5 years?

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Chua, Hannah Daile P; Hägg, Margareta Bendeus; Cheung, Lim Kwong

2010-06-01

The objective of this study was to compare the long-term stability of distraction osteogenesis (DO) and conventional orthognathic surgery (CO) in patients with cleft lip and palate (CLP). CLP patients requiring maxillary advancement of 4 to 10 mm were randomized and assigned to either CO or DO. In the CO group, the maxilla was fully mobilized to the preplanned position and fixed using titanium miniplates. In the DO group, the maxilla was mobilized to a limited extent and distractors were fixed on each side of the maxilla. Serial lateral cephalographs were taken for the assessment of stability at different postoperative periods up to 5 years. In the CO group, the maxilla relapsed backward and upward, whereas in the DO group, it advanced more forward and downward over 5 years. Distraction of the cleft maxilla can achieve better long-term skeletal stability in maintaining its advanced position than CO. Copyright 2010 Mosby, Inc. All rights reserved.

Pre- and postoperative MR imaging of craniopharyngiomas

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Hald, J.K. [Rijkshospitalet, Oslo (Norway). Dept. of Radiology; Eldevik, O.P. [Rijkshospitalet, Oslo (Norway). Dept. of Neurosurgery; Quint, D.J. [Rijkshospitalet, Oslo (Norway). Dept. of Neurosurgery; Chandler, W.F. [Univ. of Michigan Hospital, Ann Arbor, MI (United States). Dept. of Radiology; Kollevold, T. [Univ. of Michigan Hospital, Ann Arbor, MI (United States). Dept. of Neurosurgery

1996-09-01

Purpose: To compare the pre- and postoperative MR appearance of craniopharyngiomas with respect to lesion size, tumour morphology and identification of surrounding normal structures. Material and Methods: MR images obtained prior to and following craniopharyngioma resection were evaluated retrospectively in 10 patients. Tumour signal charcteristics, size and extension with particular reference to the optic chiasm, the pituitary gland, the pituitary stalk and the third ventricle were evaluated. Results: Following surgery, tumour volume was reduced in all patients. In 6 patients there was further tumour volume reduction between the first and second postoperative images. Two of these patients received radiation therapy between the 2 postoperative studies, while 4 had no adjuvant treatment to the surgical intervention. There was improved visualization of the optic chiasm, in 3, the pituitary stalk in one, and the third ventricle in 9 of the 10 patients. The pituitary gland was identified preoperatively only in one patient, postoperatively only in another, pre- and postoperatively in 5, and neither pre- nor postoperatively in 3 patients. In 3 patients MR imaging 0-7 days postoperatively identified tumour remnants not seen at the end of the surgical procedure. The signal intensities of solid and cystic tumour components were stable from pre- to the first postoperative MR images. Optic tract increased signal prior to surgery was gone 28 days postoperatively in one patient, but persisted on the left side for 197 days after surgery in another. Conclusion: Postoperative MR imaging of craniopharyngiomas demonstrated tumour volume reduction and tumour remnants not seen at surgery. Early postoperative MR imaging of craniopharyngiomas may overestimate the size of residual tumour. Improved visualization of peritumoral structures may be achieved. (orig.).

The outcome of the postoperative radiotherapy of autonomic nerve preserving operation for lower rectal cancer

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Takahashi, Keiichi; Mori, Takeo; Yasuno, Masamichi

1997-01-01

It is unclear whether adjuvant radiotherapy before or after surgery is effective for locally advanced, resectable lower rectal cancer. This study consists of a prospective randomized trial of postoperative radiotherapy for locally advanced curatively resected lower rectal carcinoma. We divided patients into two groups, one with postoperative 50 Gy radiation therapy to pelvic wall (N=64), and the other with no radiation therapy (N=46). The 5 year disease-free rate was 61.8% in the radiation group and 70.6% in the no radiation group. There was statistically no significant difference between these two groups. The local recurrence rate was 2.7% (radiation therapy group: 1.6%, no radiation therapy group: 4.3%). This local recurrence rate was very low. These results made us suspect that postoperative radiation therapy was not always necessary to prevent local recurrence. Postoperative complications had a higher incidence in the radiation therapy group than in the no-radiation therapy group. In the radiation therapy group, 35.5% of the patients suffered from diarrhea or frequent defecation, and 10.8% from severe abdominal pain. We operated on 4 cases of radiation-induced ileal stenosis and ileus. Postoperative radiation therapy did not help prevent local recurrence even though many complications resulted. (author)

Postoperative course of chronic subdural hematoma

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Takahashi, Toshiaki; Tsubone, Kyoji; Kyuma, Yoshikazu; Kuwabara, Takeo

1983-01-01

1) Fourty cases of chronic subdural hematoma were operated on by trephination, irrigation and external drainage. Postoperative neurological recovery and decrease of hematoma cavity on CT scan were followed. 2) Operation were effective for recovery of neurological grade in 28 cases, moderately effective in 7 cases and not effective in 5 cases. 3) Withinthe tenth postoperative day, more than half residual hematoma cavity existed in 53% of examined cases. After that, more than half residual cavity existed in only 17%. 4) Preoperative feature of neurologically unimproved cases were no definite history of head trauma and water like low density of hematoma cavity. Postoperative feature was persistence of more than three fourth of residual hematoma cavity on CT scan. 5) A group of unimproved cases described above are thought to have a feature of subdural hygroma rather than subdural hematoma. When possibility of subdural hygroma is high in preoperative differential diagnosis, indication of operation should be different from chronic subdural hematoma. (author)

Postoperative Chemotherapy for Medulloblastoma

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J Gordon Millichap

2005-03-01

Full Text Available The survival rate and cognitive function of 43 children, age <3 years, with medulloblastoma treated with intensive postoperative chemotherapy alone, without radiotherapy, were determined at the University of Wurzburg and other centers in Germany Chemotherapy consisted of three two-month cycles of cyclophosphamide, methotrexate, vincristine, carboplatin, and etoposide.

Comparative Analysis between preoperative Radiotherapy and postoperative Radiotherapy in Clinical Stage I and II Endometrial Carcinoma

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Keum, Ki Chang; Lee, Chang Geol; Chung, Eun Ji; Lee, Sang Wook; Kim, Woo Cheol; Chang, Sei Kyung; Oh, Young Taek; Suh, Chang Ok; Kim, Gwi Eon

1995-01-01

Purpose : To obtain the optical treatment method in patients with endometrial carcinoma(clinical stage FIGO I, II) by comparative analysis between preoperative radiotherapy(pre-op R) and postoperative radiotherapy(post-op RT). Materials and Methods : A retrospective review of 62 endometrial carcinoma patients referred to the Yonsei Cancer Center for radiotherapy between 1985 and 1991 was undertaken. Of 62 patients, 19 patients(Stage I; 12 patients, Stage II; 7 patients) received pre-op RT before TAH(Total Abdominal Hysterectomy) and BSO(Bilateral Salphingoophorectomy) (Group 1) and 43 patients( Stage 1; 32 patients, Stage 2; 11 patients) received post-op RT after TAH and BSO (Group 2). Pre-op irradiation was given 4-6 weeks prior to surgery and post-op RT was administered on 4-5 weeks following surgery. All patients exept 1 patient(Group2; ICR alone) received external irradiation. Seventy percent(13/19) of pre-op RT group and 54 percent(23/42) of post-op RT group received external pelvic irradiation and intracavitary radiation therapy(ICR). External radiation dose was 39.6-55Gy(median 45Gy) in 5-6 week through opposed AP/PA fields or 4-field box technique treating daily, five days per week, 180cGy per fraction. ICR doses were prescribed to point A(20-39.6 Gy, median 39Gy) in Group 1 and 0.5cm depth from vaginal surface (18-30 Gy, median 21Gy) in Group2. Results : The overall 5 year survival rate was 95%. No survival difference between pre-op and post-op RT group.(89.3% vs 97.7%, p>0.1) There was no survival difference by stage, grade and histology between two groups. The survival rate was not affected by presence of residual tumor of surgical specimen after pre-op RT in Group 1(p>0.1), but affected by presence of lymph node metastasis in post-op RT group(p<0.5). The complication rate of pre-op RT group was higher than post-op RT.(16% vs 5%) Conclusion : Post-op radiotherapy offers the advantages of accurate surgical-pathological staging and low complication rate

Residual urine output and postoperative mortality in maintenance hemodialysis patients.

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Lin, Yu-Feng; Wu, Vin-Cent; Ko, Wen-Je; Chen, Yih-Sharng; Chen, Yung-Ming; Li, Wen-Yi; Chou, Nai-Kuan; Chao, Anne; Huang, Tao-Min; Chang, Fan-Chi; Chen, Shih-I; Shiao, Chih-Chung; Wang, Wei-Jie; Tsai, Hung-Bin; Tsai, Pi-Ru; Hu, Fu-Chang; Wu, Kwan-Dun

2009-09-01

The relationship between residual urine output and postoperative survival in maintenance hemodialysis patients is unknown. To explore the relationship between amount of urine before surgery and postoperative mortality and differences between postoperative nonanuria and anuria in maintenance hemodialysis patients. A total of 109 maintenance hemodialysis patients underwent major operations. Anuria was defined as urine output <30 mL in the 8 hours before the first session of postoperative dialysis. Propensity scores for postoperative anuria were developed. Postoperative residual urine output was 159.2 mL/8 h (SD, 115.1) in 33 patients; 76 patients were anuric. Preoperative residual urine output and adequate perioperative blood transfusion were positively related to postoperative urine output. Propensity-adjusted 30-day mortality was associated with postoperative anuria (odds ratio [OR], 4.56; 95% confidence interval [CI], 1.16-17.96; P = .03), prior stroke (OR, 4.46; 95% CI, 1.43-13.89; P = .01) and higher disease severity (OR, 1.10; 95% CI, 1.00-1.21; P = .049) at the first postoperative dialysis. OR of 30-day mortality was 5.38 for nonanuria to anuria vs nonanuria to nonanuria (P = .03) and 5.13 for preoperative anuria vs nonanuria to nonanuria (P = .01). By Kaplan-Meier analysis, 30-day mortality differed significantly among patients for nonanuria to nonanuria, anuria, and nonanuria to anuria (log rank, P = .045). Patients with preoperative nonanuria and postoperative anuria had higher mortality than did patients with no anuria before and after surgery and patients with anuria before surgery. Postoperative residual urine output is an important surrogate marker for disease severity.

Using the Chinese version of Memorial Delirium Assessment Scale to describe postoperative delirium after hip surgery

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Zhongyong eShi

2014-11-01

Full Text Available Objective: Memorial Delirium Assessment Scale (MDAS assesses severity of delirium. However, whether the MDAS can be used in a Chinese population is unknown. Moreover, the optimal postoperative MDAS cutoff point for describing postoperative delirium in Chinese remains largely to be determined. We therefore performed a pilot study to validate MDAS in the Chinese language and to determine the optimal postoperative MDAS cutoff point for delirium. Methods: Eighty-two patients (80 ± 6 years, 18% male who had hip surgery under general anesthesia were enrolled. The Confusion Assessment Method (CAM and Mini-mental state examination (MMSE were administered in the patients before surgery. The CAM and MDAS were performed in the patients on the first, second, and fourth postoperative day. The reliability and validity of the MDAS were determined. Receiver operating characteristic (ROC curve was used to determine the optimal Chinese version MDAS cutoff point for the identification of delirium. Results: The Chinese version of the MDAS had satisfactory internal consistency (α = 0.910. ROC analysis obtained an average optimal MDAS cutoff point of 7.5 in describing the CAM-defined postoperative delirium with an area under the ROC of 0.990 (95% CI 0.977-1.000, P < 0.001. Conclusions: The Chinese version of MDAS had good reliability and validity. The patients whose postoperative Chinese version of MDAS cutoff point was 7.5 would likely have postoperative delirium. These results have established a system for a future larger scale study.

Risk Factors for the Postoperative Recurrence of Instability After Arthroscopic Bankart Repair in Athletes.

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Nakagawa, Shigeto; Mae, Tatsuo; Sato, Seira; Okimura, Shinichiro; Kuroda, Miki

2017-09-01

Several risk factors for the postoperative recurrence of instability after arthroscopic Bankart repair have been reported, but there have been few detailed investigations of the specific risk factors in relation to the type of sport. This study investigated the postoperative recurrence of instability after arthroscopic Bankart repair without additional reinforcement procedures in competitive athletes, including athletes with a large glenoid defect. The purpose of this study was to investigate risk factors related to the postoperative recurrence of instability in athletes. Case-control study; Level of evidence, 3. A total of 115 athletes (123 shoulders) were classified into 5 groups according to type of sport: rugby (41 shoulders), American football (32 shoulders), other collision sports (18 shoulders), contact sports (15 shoulders), and overhead sports (17 shoulders). First, the recurrence rate in each sporting category was investigated, with 113 shoulders followed up for a minimum of 2 years. Then, factors related to postoperative recurrence were investigated in relation to the type of sport. Postoperative recurrence of instability was noted in 23 of 113 shoulders (20.4%). The recurrence rate was 33.3% in rugby, 17.2% in American football, 11.1% in other collision sports, 14.3% in contact sports, and 12.5% in overhead sports. The most frequent cause of recurrence was tackling, and recurrence occurred with tackling in 12 of 16 athletes playing rugby or American football. Reoperation was completed in 11 shoulders. By univariate analysis, significant risk factors for postoperative recurrence of instability included playing rugby, age between 10 and 19 years at surgery, preoperative glenoid defect, small bone fragment of bony Bankart lesion, and capsular tear. However, by multivariate analysis, the most significant factor was not the type of sport but younger age at operation and a preoperative glenoid defect with small or no bone fragment. Compared with the other

Experience with early postoperative feeding after abdominal aortic surgery.

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Ko, Po-Jen; Hsieh, Hung-Chang; Liu, Yun-Hen; Liu, Hui-Ping

2004-03-01

Abdominal aortic surgery is a form of major vascular surgery, which traditionally involves long hospital stays and significant postoperative morbidity. Experiences with transit ileus are often encountered after the aortic surgery. Thus traditional postoperative care involves delayed oral feeding until the patients regain their normal bowel activities. This report examines the feasibility of early postoperative feeding after abdominal aortic aneurysm (AAA) open-repair. From May 2002 through May 2003, 10 consecutive patients with infrarenal AAA who underwent elective surgical open-repair by the same surgeon in our department were reviewed. All of them had been operated upon and cared for according to the early feeding postoperative care protocol, which comprised of adjuvant epidural anesthesia, postoperative patient controlled analgesia, early postoperative feeding and early rehabilitation. The postoperative recovery and length of hospital stay were reviewed and analyzed. All patients were able to sip water within 1 day postoperatively without trouble (Average; 12.4 hours postoperatively). All but one patient was put on regular diet within 3 days postoperatively (Average; 2.2 days postoperatively). The average postoperative length of stay in hospital was 5.8 days. No patient died or had major morbidity. Early postoperative feeding after open repair of abdominal aorta is safe and feasible. The postoperative recovery could be improved and the length of stay reduced by simply using adjuvant epidural anesthesia during surgery, postoperative epidural patient-controlled analgesia, early feeding, early ambulation, and early rehabilitation. The initial success of our postoperative recovery program of aortic repair was demonstrated.

Does hybrid fixation prevent junctional disease after posterior fusion for degenerative lumbar disorders? A minimum 5-year follow-up study.

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Baioni, Andrea; Di Silvestre, Mario; Greggi, Tiziana; Vommaro, Francesco; Lolli, Francesco; Scarale, Antonio

2015-11-01

Medium- to long-term retrospective evaluation of clinical and radiographic outcome in the treatment of degenerative lumbar diseases with hybrid posterior fixation. Thirty patients were included with the mean age of 47.8 years (range 35 to 60 years). All patients underwent posterior lumbar instrumentation using hybrid fixation for lumbar stenosis with instability (13 cases), degenerative spondylolisthesis Meyerding grade I (6 cases), degenerative disc disease of one or more adjacent levels in six cases and mild lumbar degenerative scoliosis in five patients. Clinical outcomes were evaluated using Oswestry disability index (ODI), Roland and Morris disability questionnaire (RMDQ), and the visual analog scale (VAS) pain scores. All patients were assessed by preoperative, postoperative and follow-up standing plain radiographs and lateral X-rays with flexion and extension. Adjacent disc degeneration was also evaluated by magnetic resonance imaging (MRI) at follow-up. At a mean follow-up of 6.1 years, we observed on X-rays and/or MRI 3 cases of adjacent segment disease (10.0 %): two of them (6.6 %) presented symptoms and recurred a new surgery. The last patient (3.3 %) developed asymptomatic retrolisthesis of L3 not requiring revision surgery. The mean preoperative ODI score was 67.6, RMDQ score was 15.1, VAS back pain score was 9.5, and VAS leg pain score was 8.6. Postoperatively, these values improved to 28.1, 5.4, 3.1, and 2.9, respectively, and remained substantially unchanged at the final follow-up: (27.7, 5.2, 2.9, and 2.7, respectively). After 5-year follow-up, hybrid posterior lumbar fixation presented satisfying clinical outcomes in the treatment of degenerative disease.

Fourteen-Year Long-Term Results after Gastric Banding

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Christine Stroh

2011-01-01

Full Text Available Background. Gastric banding (GB is a common bariatric procedure that is performed worldwide. Weight loss can be substantial after this procedure, but it is not sufficient in a significant portion of patients. Long-term rates for associated complications increase with every year of follow up, and only a few long-term studies have been published that examine these rates. We present our results after 14 years of postoperative follow up. Methods. Two hundred patients were operated upon form 01.02.1995 to 31.01.2009. Data collection was performed prospectively. In retrospective analysis, we analyzed weight loss, short- and long-term complications, amelioration of comorbidities and long-term outcome. Results. The mean postoperative follow up time was 94.4 months (range 2–144. The follow up rate was 83.5%. The incidence of postoperative complications for slippage was 2.5%, for pouch dilatation was 9.5%, for band migration was 5.5% and 12.0% for overall band removal. After 14 years, the reoperation rate was 30.5% with a reoperation rate of 2.2% for every year of follow up. Excess weight loss was 40.2% after 1 year, 46.3% after 2 years, 45.9% after 3 years, 41.9% after five years, 33.3% after 8 years, 30.8% after 10 years, 33.3% after 12 years and 15.6% after 14 years of follow up. Conclusion. The complication and reoperation rate after GB is high. Nevertheless, GB is still a therapeutic option in morbid obese patients, but the criteria for patient selection should be carefully evaluated.

Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

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Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsuneyama, Koichi [Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Sugitani, Toyama 930‐0194 (Japan); Endo, Shinya [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsukui, Tohru [Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka 350‐1241 (Japan); Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@p.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan)

2012-10-01

Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

International Nuclear Information System (INIS)

Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

2012-01-01

Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

Postoperative dental morbidity in children following dental treatment under general anesthesia.

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Hu, Yu-Hsuan; Tsai, Aileen; Ou-Yang, Li-Wei; Chuang, Li-Chuan; Chang, Pei-Ching

2018-05-10

General anesthesia has been widely used in pediatric dentistry in recent years. However, there remain concerns about potential postoperative dental morbidity. The goal of this study was to identify the frequency of postoperative dental morbidity and factors associated with such morbidity in children. From March 2012 to February 2013, physically and mentally healthy children receiving dental treatment under general anesthesia at the Department of Pediatric Dentistry of the Chang Gung Memorial Hospital in Taiwan were recruited. This was a prospective and observational study with different time evaluations based on structured questionnaires and interviews. Information on the patient demographics, anesthesia and dental treatment performed, and postoperative dental morbidity was collected and analyzed. Correlations between the study variables and postoperative morbidity were analyzed based on the Pearson's chi-square test. Correlations between the study variables and the scale of postoperative dental pain were analyzed using the Mann-Whitney U test. Fifty-six pediatric patients participated in this study, with an average age of 3.34 ± 1.66 years (ranging from 1 to 8 years). Eighty-two percent of study participants reported postoperative dental pain, and 23% experienced postoperative dental bleeding. Both dental pain and bleeding subsided 3 days after the surgery. Dental pain was significantly associated with the total number of teeth treated, while dental bleeding, with the presence of teeth extracted. Patients' gender, age, preoperative dental pain, ASA classification, anesthesia time, and duration of the operation were not associated with postoperative dental morbidity. Dental pain was a more common postoperative dental morbidity than bleeding. The periods when parents reported more pain in their children were the day of the operation (immediately after the procedure) followed by 1 day and 3 days after the treatment.

Detection of a negative correlation between prescription of Chinese herbal products containing coumestrol, genistein or daidzein and risk of subsequent endometrial cancer among tamoxifen-treated female breast cancer survivors in Taiwan between 1998 and 2008: A population-based study.

Science.gov (United States)

Hu, Yi-Cheng; Wu, Chien-Tung; Lai, Jung-Nien; Tsai, Yueh-Ting

2015-07-01

Tamoxifen users sometimes seek complementary and alternative medicine advice for treatment of a variety of illness and co-administer with phytoestrogen-containing herbs, resulting in an increasing concern of its influence in subsequent endometrial cancer risk. Our study aims to determine the prevalence of Chinese herbal products containing coumestrol, genistein, or daidzein and their association with subsequent endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. We selected all patients who were newly diagnosed with invasive breast cancer and received tamoxifen treatment between January 1, 1998, and December 31, 2008, from the National Health Insurance Research Database. Among the 26,656 tamoxifen-treated breast cancer survivors, we evaluated the usage, frequency of service, and prescription of Chinese herbal products containing coumestrol, genistein, or daidzein. The logistic regression method was employed to calculate the odds ratios for utilization of those herbal products. Cox proportional hazard regression was set to calculate the hazard ratios of endometrial cancer associated with such usage. Of the patients surveyed, 36.2% (n=9652) of the tamoxifen-treated breast cancer survivors examined in the study had consumed Chinese herbal products containing coumestrol, genistein, or daidzein during the study period. Exposure to Ge Gen(Puerariae Radix) specifically was the most extensive. For it, the population consumed an average cumulative dose of above 180g. Compared to those who had never used Chinese herbal products, breast cancer survivors who had taken Chinese herbal products containing coumestrol, genistein, or daidzein concurrently with tamoxifen treatment did not have a higher hazard ratio for subsequent development of endometrial cancer. Among those tamoxifen-treated female breast cancer survivors in Taiwan, consumption of Chinese herbal products containing coumestrol, genistein, or daidzein is negatively correlated with

Therapeutic options and postoperative wound complications after extremity soft tissue sarcoma resection and postoperative external beam radiotherapy.

Science.gov (United States)

Abouarab, Mohamed H; Salem, Iman L; Degheidy, Magdy M; Henn, Dominic; Hirche, Christoph; Eweida, Ahmad; Uhl, Matthias; Kneser, Ulrich; Kremer, Thomas

2018-02-01

Soft tissue sarcomas occur most commonly in the lower and upper extremities. The standard treatment is limb salvage surgery combined with radiotherapy. Postoperative radiotherapy is associated with wound complications. This systematic review aims to summarise the available evidence and review the literature of the last 10 years regarding postoperative wound complications in patients who had limb salvage surgical excision followed by direct closure vs flap coverage together with postoperative radiotherapy and to define the optimal timeframe for adjuvant radiotherapy after soft tissue sarcomas resection and flap reconstruction. A literature search was performed using PubMed. The following keywords were searched: limb salvage, limb-sparing, flaps, radiation therapy, radiation, irradiation, adjuvant radiotherapy, postoperative radiotherapy, radiation effects, wound healing, surgical wound infection, surgical wound dehiscence, wound healing, soft tissue sarcoma and neoplasms. In total, 1045 papers were retrieved. Thirty-seven articles were finally selected after screening of abstracts and applying dates and language filters and inclusion and exclusion criteria. Plastic surgery provides a vast number of reconstructive flap procedures that are directly linked to decreasing wound complications, especially with the expectant postoperative radiotherapy. This adjuvant radiotherapy is better administered in the first 3-6 weeks after reconstruction to allow timely wound healing and avoid local recurrence. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Outcome of postoperative radiotherapy following radical prostatectomy: a single institutional experience

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Lee, Sea Won; Chung, Mi Joo; Jeong, Song Mi; Kim, Sung Hwan; Lee, Jong Hoon [Dept.of Radiation Oncology, St. Vincent' s Hospital, The Catholic University of Korea College of Medicine, Suwon (Korea, Republic of); Hwang, Tae Kon; Hong, Sung Hoo; Lee, Ji Youl; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Yoon, Sei Chul [Dept.of Radiation Oncology, Bucheon St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Bucheon (Korea, Republic of)

2014-09-15

This single institutional study is aimed to observe the outcome of patients who received postoperative radiotherapy after radical prostatectomy. A total of 59 men with histologically identified prostate adenocarcinoma who had received postoperative radiation after radical prostatectomy from August 2005 to July 2011 in Seoul St. Mary's Hospital of the Catholic University of Korea, was included. They received 45-50 Gy to the pelvis and boost on the prostate bed was given up to total dose of 63-72 Gy (median, 64.8 Gy) in conventional fractionation. The proportion of patients given hormonal therapy and the pattern in which it was given were analyzed. Primary endpoint was biochemical relapse-free survival (bRFS) after radiotherapy completion. Secondary endpoint was overall survival (OS). Biochemical relapse was defined as a prostate-specific antigen level above 0.2 ng/mL. After median follow-up of 53 months (range, 0 to 104 months), the 5-year bRFS of all patients was estimated 80.4%. The 5-year OS was estimated 96.6%. Patients who were given androgen deprivation therapy had a 5-year bRFS of 95.1% while the ones who were not given any had that of 40.0% (p < 0.01). However, the statistical significance in survival difference did not persist in multivariate analysis. The 3-year actuarial grade 3 chronic toxicity was 1.7% and no grade 3 acute toxicity was observed. The biochemical and toxicity outcome of post-radical prostatectomy radiotherapy in our institution is favorable and comparable to those of other studies.

Comparing the Effectiveness of Sagittal Balance, Foraminal Stenosis, and Preoperative Cord Rotation in Predicting Postoperative C5 Palsy.

Science.gov (United States)

Chugh, Arunit J S; Weinberg, Douglas S; Alonso, Fernando; Eubanks, Jason D

2017-11-01

Retrospective cohort review. To determine whether preoperative cord rotation is independently correlated with C5 palsy when analyzed alongside measures of sagittal balance and foraminal stenosis. Postoperative C5 palsy is a well-documented complication of cervical procedures with a prevalence of 4%-8%. Recent studies have shown a correlation with preoperative spinal cord rotation. There have been few studies, however, that have examined the role of sagittal balance and foraminal stenosis in the development of C5 palsy. A total of 77 patients who underwent cervical decompression-10 of whom developed C5 palsy-were reviewed. Sagittal balance was assessed using curvature angle and curvature index on radiographs and magnetic resonance image (MRI). Cord rotation was assessed on axial MRI. C4-C5 foraminal stenosis was assessed on sagittal MRI using area measurements and a grading scale. Demographics and information on surgical approach were gathered from chart review. Correlation with C5 palsy was performed by point-biserial, χ, and regression analyses. Point-biserial analysis indicated that only cord rotation showed significance (Pbalance did not correlate with presence of C5 palsy. Logistic regression model yielded cord rotation as the only significant independent predictor of C5 palsy. For every degree of axial cord rotation, the likelihood ratio for suffering a C5 palsy was 3.93 (95% confidence interval, 2.01-8.66; Ppoints to mechanisms other than direct compression as the etiology. In addition, the lack of correlation with postoperative changes in sagittal balance hints that measures of curvature angle and curvature index may not be appropriate to accurately predict this complication. Level 3.

An analysis of postoperative hemoglobin levels in patients with a fractured neck of femur.

Science.gov (United States)

Nagra, Navraj S; van Popta, Dmitri; Whiteside, Sigrid; Holt, Edward M

2016-10-01

The aim of this study was to analyze the changes in hemoglobin level and to determine a suitable timeline for post-operative hemoglobin monitoring in patients undergoing fixation of femoral neck fracture. Patients who underwent either dynamic hip screw (DHS) fixation (n = 74, mean age: 80 years) or hip hemiarthroplasty (n = 104, mean age: 84 years) for femoral neck fracture were included into the study. The hemoglobin level of the patients was monitored perioperatively. Analysis found a statistically and clinically significant mean drop in hemoglobin of 31.1 g/L over time from pre-operatively (D0) to day-5 post-operatively (p hemoglobin values over hemiarthroplasty patients (p = 0.046). The decrease in hemoglobin in the first 24-h post-operative period (D0 to day-1) is an underestimation of the ultimate lowest value in hemoglobin found at day-2. Relying on the day-1 hemoglobin could be detrimental to patient care. We propose a method of predicting patients likely to be transfused, and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring. Level IV Prognostic study. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

Efeito do tamoxifeno no perfil das proteínas plasmáticas em condição de diabetes mellitus tipo 1 Effect of tamoxifen on plasma proteins in diabetes mellitus type 1

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Teresa Cristina P. Silva

2005-01-01

Full Text Available OBJETIVO: Considerando-se que importantes avanços científicos têm sido obtidos através de estudos com Diabetes mellitus experimental, e que a ação do tamoxifeno em humanos permanece obscura, o presente trabalho objetiva acompanhar as modificações promovidas pelo diabetes e tamoxifeno no perfil eletroforético das proteínas plasmáticas. MÉTODOS: Foram utilizados 27 ratos fêmeas Wistar (180-220g peso corporal, divididos randomicamente em 5 grupos: C1 (n=3, receberam veículo, C2 (n=3, sem tratamento, T (n=5, tratados com tamoxifeno, 0,3mg/kg/dia, D (n=8, diabéticos experimentais por estreptozotocina, 45mg/Kg e DT (n=8, diabéticos tratados com tamoxifeno. A eletroforese foi realizada em acetato de celulose, pH 8,6-8,8, cuba TECNOW, e as fitas foram coradas em Ponceau S. As proteínas totais foram determinadas pelo método do Biureto (Kit Labtest. Os proteinogramas foram obtidos em densitômetro BioSystems BTS-235. RESULTADOS: Albumina diminuiu progressivamente nos grupos T, D e DT; a fração a1 aumentou nos grupos T e DT; a fração a2 aumentou nos grupos T e D, havendo efeito aditivo no grupo DT; a fração b aumentou nos grupos T e D; a fração g aumentou nos grupos T, D e DT. CONCLUSÃO: Os resultados indicam uma resposta de fase aguda, com efeito aditivo do tamoxifeno e diabetes, sugerindo uma provável lesão hepática.PURPOSE: Considering that important scientific advances have been obtained through studies based on experimental Diabetes mellitus, and that tamoxifen action in humans remains unknown, the aim of the present work is to follow the modifications promoted by diabetes and tamoxifen in the electrophoretic profile of plasmatic proteins. METHODS: It was used 27 Wistar female rats (180-250 body weight, randomicaly divided into five groups: C1 (n=3, received vehicle, C2 (n=3, no treatment, T (n=5, treated with tamoxifen, 0.3mg/Kg/day, D (n=8, experimental diabetes by estreptozotocin, 45mg/Kg and DT (n=8, diabetic treated

Association between baseline cognitive impairment and postoperative delirium in elderly patients undergoing surgery for adult spinal deformity.

Science.gov (United States)

Adogwa, Owoicho; Elsamadicy, Aladine A; Vuong, Victoria D; Fialkoff, Jared; Cheng, Joseph; Karikari, Isaac O; Bagley, Carlos A

2018-01-01

OBJECTIVE Postoperative delirium is common in elderly patients undergoing spine surgery and is associated with a longer and more costly hospital course, functional decline, postoperative institutionalization, and higher likelihood of death within 6 months of discharge. Preoperative cognitive impairment may be a risk factor for the development of postoperative delirium. The aim of this study was to investigate the relationship between baseline cognitive impairment and postoperative delirium in geriatric patients undergoing surgery for degenerative scoliosis. METHODS Elderly patients 65 years and older undergoing a planned elective spinal surgery for correction of adult degenerative scoliosis were enrolled in this study. Preoperative cognition was assessed using the validated Saint Louis University Mental Status (SLUMS) examination. SLUMS comprises 11 questions, with a maximum score of 30 points. Mild cognitive impairment was defined as a SLUMS score between 21 and 26 points, while severe cognitive impairment was defined as a SLUMS score of ≤ 20 points. Normal cognition was defined as a SLUMS score of ≥ 27 points. Delirium was assessed daily using the Confusion Assessment Method (CAM) and rated as absent or present on the basis of CAM. The incidence of delirium was compared in patients with and without baseline cognitive impairment. RESULTS Twenty-two patients (18%) developed delirium postoperatively. Baseline demographics, including age, sex, comorbidities, and perioperative variables, were similar in patients with and without delirium. The length of in-hospital stay (mean 5.33 days vs 5.48 days) and 30-day hospital readmission rates (12.28% vs 12%) were similar between patients with and without delirium, respectively. Patients with preoperative cognitive impairment (i.e., a lower SLUMS score) had a higher incidence of postoperative delirium. One- and 2-year patient reported outcomes scores were similar in patients with and without delirium. CONCLUSIONS