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Sample records for long-term progression-free survival

  1. Foreign Ownership and Long-term Survival

    DEFF Research Database (Denmark)

    Kronborg, Dorte; Thomsen, Steen

    2006-01-01

    probability. On average exit risk for domestic companies is 2.3 times higher than for foreign companies. First movers like Siemens, Philips, Kodak, Ford, GM or Goodyear have been active in the country for almost a century. Relative foreign survival increases with company age. However, the foreign survival...

  2. Long-term patient survival in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Flossmann, Oliver; Berden, Annelies; de Groot, Kirsten

    2011-01-01

    Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain.......Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain....

  3. Long-term survival in small-cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U; Osterlind, K; Hansen, M

    1995-01-01

    PURPOSE: To describe in patients with small-cell lung cancer (SCLC) the characteristics of those who survive for > or = 5 years, to identify long-term prognostic factors, to analyze survival data of 5-year survivors, and to study 10-year survival in patients entered before 1981. PATIENTS......, especially tobacco-related cancers and other tobacco-related diseases....

  4. Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

    Science.gov (United States)

    Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

    2009-01-01

    In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

  5. Long-term survival and causes of death after stroke

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik; Davidsen, M; Thorvaldsen, P

    2001-01-01

    As part of the Danish contribution to the World Health Organization (WHO) MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Project, a register of patients with stroke was established in 1982. The purpose of the present study was to analyze long-term survival and causes of death...

  6. Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

    DEFF Research Database (Denmark)

    Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle

    2010-01-01

    To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer...

  7. Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

    DEFF Research Database (Denmark)

    Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle

    2010-01-01

    To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-a trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, ß-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer...

  8. Long-term Survival after Metastatic Childhood Melanoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; Bybjerg Jensen, Mette; Krag, Christen

    2014-01-01

    SUMMARY: Malignant melanoma in children is very rare and accounts for only 1-3% of all melanomas. A congenital melanocytic nevus depending on the size of the lesion is one of the risk factors for developing childhood melanoma because of the possible malignant transformation. Childhood malignant...... of malign melanoma must be in mind when evaluating a pigmented lesion in a pediatric patient. We present a case of a patient born with a congenital nevus diagnosed with metastatic childhood malignant scalp melanoma at the age of 6 years. The patient underwent surgical ablation and reconstruction and has...... survived 26 years without recurrence, thus representing an uplifting case of long-term survival of childhood melanoma....

  9. Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Beauchemin C

    2014-06-01

    Full Text Available Catherine Beauchemin,1 Dan Cooper,2 Marie-Ève Lapierre,1 Louise Yelle,3 Jean Lachaine11Université de Montréal, Faculté de pharmacie, Montreal, 2Institut national d'excellence en santé et en services sociaux (INESSS, 3Centre Hospitalier de l'Université de Montréal – Hôpital Notre-Dame, Département de médecine, Université de Montréal, Montreal, QC, CanadaBackground: Progression-free survival (PFS and time to progression (TTP are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS remains a matter of uncertainty in metastatic breast cancer (mBC. This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach.Methods: We conducted a systematic literature review according to the PICO method: 'Population' consisted of women with mBC; 'Interventions' and 'Comparators' were standard treatments for mBC or best supportive care; 'Outcomes' of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP.Results: A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01. Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01. The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172 + 1.753 (95% CI 1.307–2.198 × ΔPFS (R2=0.86.Conclusion: Results of

  10. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival.

    LENUS (Irish Health Repository)

    2012-02-01

    Aims: Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.

  11. Long-term survival of methotrexate in psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    N. Battafarano

    2011-06-01

    Full Text Available Objective. The purpose of this study was to evaluate the long-term survival rate of Methotrexate (MTX in the peripheral joint involvement of psoriatic arthritis (PsA in a setting of everyday clinical practice. Methods. This was an observational restrospective study performed using the data from a dermatological-rheumatological PsA clinic. All of the patients evaluated at this clinic from March 1997 to December 2007 who were started on MTX alone, had a three-year follow-up time or had discontinued the therapy were included into the survey. Results. Of the 174 evaluable patients, 104 (59.8% were still taking MTX after three years of treament. The reasons of therapy discontinuation in the remaining 70 (40.2% patients were: 34 (19.5% lost-to-follow-up, 18 (10.3% adverse events, 14 (8% inefficacies, and 4 (2.3% deaths (none related to the therapy. MTX was effective in controlling joint inflammation but not in preventing their deterioration. Overall, adverse events were recorded in 43 patients (36.4% of the 114 patients with a three-year follow-up. No serious side effect occurred in the study population. Conclusions. The results of this study showed that, in a setting of clinical pratice, MTX had a good three-year performance in patients with peripheral PsA. Almost 60% of them were still taking this drug at the end of the study period and the toxicity was more than acceptable. In our opinion, MTX might be considered the non-biological DMARD of choice for the treatment of this condition. However it should be used earlier and at higher doses.

  12. Missing data and censoring in the analysis of progression-free survival in oncology clinical trials.

    Science.gov (United States)

    Denne, J S; Stone, A M; Bailey-Iacona, R; Chen, T-T

    2013-01-01

    Progression-free survival (PFS) is increasingly used as a primary endpoint in oncology clinical trials. However, trial conduct is often such that PFS data on some patients may be partially missing either due to incomplete follow-up for progression, or due to data that may be collected but confounded by patients stopping randomized therapy or starting alternative therapy prior to progression. Regulatory guidance on how to handle these patients in the analysis and whether to censor these patients differs between agencies. We present results of a reanalysis of 28 Phase III trials from 12 companies or institutions performed by the Pharmaceutical Research and Manufacturers Association-sponsored PFS Expert Team. We show that analyses not adhering to the intention-to-treat principle tend to give hazard ratio estimates further from unity and describe several factors associated with this shift. We present illustrative simulations to support these findings and provide recommendations for the analysis of PFS.

  13. Long-Term Survival of Enteric Microorganisms in Frozen Wastewater

    Science.gov (United States)

    2002-10-01

    sewage.............31 Table 12. Percentage of cysts of Giardia muris recovered after one and three cycles of freezing and thawing...of Giardia muris and Giardia lamblia that had been subjected to one to three cycles of freezing at –16°C and thawing at 20°C. Examination Long-Term... Giardia muris recovered after one and three cycles of freezing and thawing. (From Erlandsen et al. 1990.)a Number of freeze–thaw cycles Initial

  14. Long-term survival of adult trauma patients.

    Science.gov (United States)

    Davidson, Giana H; Hamlat, Christian A; Rivara, Frederick P; Koepsell, Thomas D; Jurkovich, Gregory J; Arbabi, Saman

    2011-03-09

    Inpatient trauma case fatality rates may provide an incomplete assessment for overall trauma care effectiveness. To date, there have been few large studies evaluating long-term mortality in trauma patients and identifying predictors that increase risk for death following hospital discharge. To determine the long-term mortality of patients following trauma admission and to evaluate survivorship in relationship with discharge disposition. Retrospective cohort study of 124,421 injured adult patients during January 1995 to December 2008 using the Washington State Trauma Registry linked to death certificate data. Kaplan-Meier and Cox proportional hazards models were used to evaluate long-term mortality following hospital admission for trauma. Of the 124,421 trauma patients, 7243 died before hospital discharge and 21,045 died following hospital discharge. Cumulative mortality at 3 years postinjury was 16% (95% confidence interval [CI], 15.8%-16.2%) compared with the expected population cumulative mortality of 5.9% (95% CI, 5.9%-5.9%). In-hospital mortality improved during the 14-year study period from 8% (n = 362) to 4.9% (n = 600), whereas long-term cumulative mortality increased from 4.7% (95% CI, 4.1%-5.4%) to 7.4% (95% CI, 6.8%-8.1%). After adjustments for confounders, patients who were older and those who were discharged to a skilled nursing facility had the highest risk of death. The adjusted hazard ratios (HRs) for death after discharge to a skilled nursing facility compared with that after discharge home were 1.41 (95% CI, 0.72-2.76) for patients aged 18 to 30 years, 1.92 (95% CI, 1.36-2.73) for patients aged 31 to 45 years, 2.02 (95% CI, 1.39-2.93) for patients aged 46 to 55 years, 1.93 (95% CI, 1.40-2.64) for patients aged 56 to 65 years, 1.49 (95% CI, 1.14-1.94) for patients aged 66 to 75 years, 1.54 (95% CI, 1.27-1.87) for patients aged 76 to 80 years, and 1.38 (95% CI, 1.09-1.74) for patients older than 80 years. Other significant predictors of mortality

  15. Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL

    DEFF Research Database (Denmark)

    Geisler, Christian H; van T' Veer, Mars B; Jurlander, Jesper

    2014-01-01

    .3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529....

  16. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

    Science.gov (United States)

    Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

    2016-09-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

  17. Foraminiferal survival after long term experimentally induced anoxia

    Science.gov (United States)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-06-01

    Anoxia has been successfully induced in four benthic chambers installed on the Northern Adriatic seafloor from 1 week to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerGreen method has been applied. Numerous individuals have been found living at all sampling times and at all sampling depths, showing that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulphides. However, foraminiferal standing stocks decrease with sampling time in an irregular way. A large difference in standing stock between two cores samples in initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after 1 month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in a core sampled after 2 months of anoxia, to attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulphides, but rather due to a continuous diminution of labile organic matter.

  18. Prognostic Factors and Decision Tree for Long-term Survival in Metastatic Uveal Melanoma.

    Science.gov (United States)

    Lorenzo, Daniel; Ochoa, María; Piulats, Josep Maria; Gutiérrez, Cristina; Arias, Luis; Català, Jaum; Grau, María; Peñafiel, Judith; Cobos, Estefanía; Garcia-Bru, Pere; Rubio, Marcos Javier; Padrón-Pérez, Noel; Dias, Bruno; Pera, Joan; Caminal, Josep Maria

    2017-12-04

    The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree. The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion. Ophthalmic and oncological characteristics were assessed in both groups. Of the 99 patients, 62 (62.6%) were classified as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate analysis identified the following predictors of long-term survival: age ≤ 65 years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018); additionally, the size (smaller vs. larger) of the largest liver metastasis showed a trend towards significance (p=0.063). Based on the variables significantly associated with long-term survival, we developed a decision tree to facilitate clinical decision-making. The findings of this study demonstrate the existence of a bimodal survival pattern in patients with metastatic uveal melanoma. The presence of certain clinical characteristics at diagnosis of distant disease is associated with long-term survival. A decision tree was developed to facilitate clinical decision-making and to counsel patients about the expected course of disease.

  19. Intrathoracic Anastomotic Leakage after Gastroesophageal Cancer Resection Is Associated with Reduced Long-term Survival

    DEFF Research Database (Denmark)

    Kofoed, Steen Christian; Calatayud, Dan; Jensen, Lone Susanne

    2014-01-01

    BACKGROUND: Most likely because of low statistical power, no previous studies have shown any significant association between long-term survival and anastomotic leakage in patients who have undergone gastroesophageal cancer resection. MATERIAL AND METHODS: The present study included, prospectively...

  20. Impact of tumour volume on prediction of progression-free survival in sinonasal cancer

    International Nuclear Information System (INIS)

    Hennersdorf, Florian; Mauz, Paul-Stefan; Adam, Patrick; Welz, Stefan; Sievert, Anne; Ernemann, Ulrike; Bisdas, Sotirios

    2015-01-01

    The present study aimed to analyse potential prognostic factors, with emphasis on tumour volume, in determining progression free survival (PFS) for malignancies of the nasal cavity and the paranasal sinuses. Retrospective analysis of 106 patients with primary sinonasal malignancies treated and followed-up between March 2006 and October 2012. Possible predictive parameters for PFS were entered into univariate and multivariate Cox regression analysis. Kaplan-Meier curve analysis included age, sex, baseline tumour volume (based on MR imaging), histology type, TNM stage and prognostic groups according to the American Joint Committee on Cancer (AJCC) classification. Receiver operating characteristic (ROC) curve analysis concerning the predictive value of tumour volume for recurrence was also conducted. The main histological subgroup consisted of epithelial tumours (77%). The majority of the patients (68%) showed advanced tumour burden (AJCC stage III–IV). Lymph node involvement was present in 18 cases. The mean tumour volume was 26.6 ± 21.2 cm 3 . The median PFS for all patients was 24.9 months (range: 2.5–84.5 months). The ROC curve analysis for the tumour volume showed 58.1% sensitivity and 75.4% specificity for predicting recurrence. Tumour volume, AJCC staging, T- and N- stage were significant predictors in the univariate analysis. Positive lymph node status and tumour volume remained significant and independent predictors in the multivariate analysis. Radiological tumour volume proofed to be a statistically reliable predictor of PFS. In the multivariate analysis, T-, N- and overall AJCC staging did not show significant prognostic value

  1. Acute and long-term survival in chronically critically ill surgical patients: a retrospective observational study.

    Science.gov (United States)

    Hartl, Wolfgang H; Wolf, Hilde; Schneider, Christian P; Küchenhoff, Helmut; Jauch, Karl-Walter

    2007-01-01

    Various cohort studies have shown that acute (short-term) mortality rates in unselected critically ill patients may have improved during the past 15 years. Whether these benefits also affect acute and long-term prognosis in chronically critically ill patients is unclear, as are determinants relevant to prognosis. We conducted a retrospective analysis of data collected from March 1993 to February 2005. A cohort of 390 consecutive surgical patients requiring intensive care therapy for more than 28 days was analyzed. The intensive care unit (ICU) survival rate was 53.6%. Survival rates at one, three and five years were 61.8%, 44.7% and 37.0% among ICU survivors. After adjustment for relevant covariates, acute and long-term survival rates did not differ significantly between 1993 to 1999 and 1999 to 2005 intervals. Acute prognosis was determined by disease severity during ICU stay and by primary diagnosis. However, only the latter was independently associated with long-term prognosis. Advanced age was an independent prognostic determinant of poor short-term and long-term survival. Acute and long-term prognosis in chronically critically ill surgical patients has remained unchanged throughout the past 12 years. After successful surgical intervention and intensive care, long-term outcome is reasonably good and is mainly determined by age and underlying disease.

  2. Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes.

    Science.gov (United States)

    Sterkenburg, Anthe S; Hoffmann, Anika; Gebhardt, Ursel; Warmuth-Metz, Monika; Daubenbüchel, Anna M M; Müller, Hermann L

    2015-07-01

    Quality of life (QoL) and long-term prognosis are frequently, and often severely, impaired in craniopharyngioma (CP) patients. Knowledge of risk factors for long-term outcome is important for optimization of treatment. Overall survival (OS) and progression-free survival (PFS), body mass index (BMI), neuropsychological status (EORTCQLQ-C30, MFI-20), and psychosocial status were analyzed in 261 patients with childhood-onset CP diagnosed before 2000 and longitudinally observed in HIT-Endo. Twenty-year OS was lower (P = .006) in CP with hypothalamic involvement (HI) (n = 132; 0.84 ± 0.04) when compared with CP without HI (n = 82; 0.95 ± 0.04). OS was not related to degree of resection, sex, age at diagnosis, or year of diagnosis (before/after 1990). PFS (n = 168; 0.58 ± 0.05) was lower in younger patients (12 years of follow-up, patients with HI presented no further increase in BMI. QoL in CP patients with HI was impaired by obesity, physical fatigue, reduced motivation, dyspnea, diarrhea, and nonoptimal psychosocial development. OS and QoL are impaired by HI in long-term survivors of CP. HI is associated with severe obesity, which plateaus after 12 years. OS/PFS are not related to degree of resection, but gross-total resection should be avoided in cases of HI to prevent further hypothalamic damage, which exacerbates sequelae. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Predicting long-term graft survival in adult kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Brett W Pinsky

    2012-01-01

    Full Text Available The ability to accurately predict a population′s long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population′s long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS projections were calculated and com-pared with the population′s actual graft survival. The projection curves were created using a two-part estimation model that (1 fits a Kaplan-Meier survival curve immediately after transplant (Part A and (2 uses truncated observational data to model a survival function for long-term projection (Part B. Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted sur-vival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%. Excellent predictability (41.3% can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population′s long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

  4. Long-term survival results of a randomized trial comparing gemcitabine/cisplatin and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally advanced and metastatic bladder cancer

    DEFF Research Database (Denmark)

    Roberts, J. T.; Maase, Hans von der; Sengeløv, Lisa

    2006-01-01

    Purpose: To compare long-term survival in patients with locally advanced       and metastatic transitional cell carcinoma (TCC) of the urothelium treated       with gemcitabine plus cisplatin (GC) or       methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND       METHODS: Efficacy.......       CONCLUSIONS: Long-term overall and progression-free survival following       treatment with GC or MVAC are similar. These results strengthen the role       of GC as a standard of care in patients with locally advanced and       metastatic transitional-cell carcinoma (TCC)....

  5. Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and meta-analysis.

    Science.gov (United States)

    Lee, Eun-Ha; Park, Sue K; Park, Boyoung; Kim, Sung-Won; Lee, Min Hyuk; Ahn, Sei Hyun; Son, Byung Ho; Yoo, Keun-Young; Kang, Daehee

    2010-07-01

    Reports of BRCA genetic mutations and risk of death or recurrence are inconsistent. This study aimed to compare overall and disease-free breast cancer survival rates between BRCA1/2 mutation carriers and non-carriers for short-term and long-term outcomes separately. We searched the PUBMED and EMBASE databases and retrieved 452 articles using keywords that included breast cancer, BRCA mutation, and survival. Seventeen articles were selected for systematic review and among them 11 were included in our meta-analysis. We used the random-effects model to calculate the summary hazard ratio and corresponding 95% confidence interval. BRCA1 mutation carriers had significantly lower short-term and long-term overall survival rates (OSR) relative to non-carriers (HR = 1.92 [95% CI = 1.45-2.53]; 1.33 [1.12-1.58], respectively), while both short-term and long-term OSR of BRCA2 carriers did not differ from non-carriers (HR = 1.30 [95% CI = 0.95-1.76]; 1.12 [95% CI = 0.86-1.45], respectively). For short-term progression-free survival rate (PFSR), BRCA1 mutation carriers had a significantly lower rate than non-carriers (HR = 1.54 [95% CI = 1.12-2.12]), while BRCA2 mutation carriers had a similar PFSR (HR = 1.23 [95% CI = 0.96-1.58]). For long-term PFSRs, we found no significant results. Our results suggest that BRCA1 mutation decreases short-term and long-term OSRs and short-term PFSR, however, BRCA2 mutation does not affect either short-term or long-term survival rate, which is attributed to the different carcinogenic pathways for BRCA1 and BRCA2.

  6. Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

    International Nuclear Information System (INIS)

    Chen, James X.; Rose, Steven; White, Sarah B.; El-Haddad, Ghassan; Fidelman, Nicholas; Yarmohammadi, Hooman; Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita; Stashek, Kristen; Wileyto, E. Paul; Salem, Riad; Metz, David C.; Soulen, Michael C.

    2017-01-01

    PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p  50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

  7. Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

    Energy Technology Data Exchange (ETDEWEB)

    Chen, James X. [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Rose, Steven [University of San Diego Medical Center, Division of Interventional Radiology, Department of Radiology (United States); White, Sarah B. [Medical College of Wisconsin, Division of Interventional Radiology, Department of Radiology (United States); El-Haddad, Ghassan [Moffitt Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Fidelman, Nicholas [University of San Francisco Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Yarmohammadi, Hooman [Memorial Sloan Kettering Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita [Stanford University Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Stashek, Kristen [Hospital of the University of Pennsylvania, Department of Pathology (United States); Wileyto, E. Paul [University of Pennsylvania, Department of Biostatistics and Epidemiology (United States); Salem, Riad [Northwestern Memorial Hospital, Division of Interventional Radiology, Department of Radiology (United States); Metz, David C. [Hospital of the University of Pennsylvania, Division of Gastroenterology, Department of Medicine (United States); Soulen, Michael C., E-mail: michael.soulen@uphs.upenn.edu [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States)

    2017-01-15

    PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

  8. Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

    Directory of Open Access Journals (Sweden)

    Verduyn S

    2012-09-01

    Full Text Available Abstract Background Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC patients with an activating mutation in the epidermal growth factor receptor (EGFR. Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+. From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis; pemetrexed/cisplatin (Pem/Cis; paclitaxel/carboplatin (Pac/Carb in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. Methods Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS. Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. Results The Quality Adjusted progression free survival (PFS (mean, (95% credibility interval was 5.2 months (4.5; 5.8 for Gem/Cis, 5.3 months (4.6; 6.1 for Pem/Cis; 4.9 months (4.4; 5.5 for Pac/Carb and 8

  9. When palliative treatment achieves more than palliation: Instances of long-term survival after palliative radiotherapy

    Directory of Open Access Journals (Sweden)

    Madhup Rastogi

    2012-01-01

    Full Text Available Context: Palliative radiotherapy aims at symptom alleviation and improvement of quality of life. It may be effective in conferring a reasonable quantum of local control, as well as possibly prolonging survival on the short term. However, there can be rare instances where long-term survival, or even cure, results from palliative radiotherapy, which mostly uses sub-therapeutic doses. Aim: To categorize and characterize the patients with long-term survival and/or cure after palliative radiotherapy. Materials and Methods: This study is a retrospective analysis of hospital records of patients treated with palliative radiotherapy from 2001 to 2006 at the Regional Cancer Centre, Shimla. Results: Of the analyzed 963 patients who received palliative radiotherapy, 2.4% (n = 23 survived at least 5 years, with a large majority of these surviving patients (73.9%, n = 17 being free of disease. Conclusions: In addition to providing valuable symptom relief, palliative radiotherapy utilizing sub-therapeutic doses may, in a small proportion of patients, bestow long-term survival, and possibly cure. Rationally, such a favorable, but rare outcome cannot be expected with supportive care alone.

  10. Long-term survival and function after suspected gram-negative sepsis.

    Science.gov (United States)

    Perl, T M; Dvorak, L; Hwang, T; Wenzel, R P

    1995-07-26

    To determine the long-term (> 3 months) survival of septic patients, to develop mathematical models that predict patients likely to survive long-term, and to measure the health and functional status of surviving patients. A large tertiary care university hospital and an associated Veterans Affairs Medical Center. From December 1986 to December 1990, a total of 103 patients with suspected gram-negative sepsis entered a double-blind, placebo-controlled efficacy trial of monoclonal antiendotoxin antibody. Of these, we followed up 100 patients for 7667 patient-months. Beginning in May 1992, we reviewed hospital records and contacted all known survivors. We measured the health status of all surviving patients. The determinants of long-term survival (up to 6 years) were identified through two Cox proportional hazard regression models: one that included patient characteristics identified at the time of sepsis (bedside model) and another that included bedside, infection-related, and treatment characteristics (overall model). Of the 60 patients in the cohort who died at a median interval of 30.5 days after sepsis, 32 died within the first month of the septic episode, seven died within 3 months, and four more died within 6 months. In the bedside multivariate model constructed to predict long-term survival, large hazard ratios (HRs) were associated with severity of underlying illness as classified by McCabe and Jackson criteria (for rapidly fatal disease, HR = 30.4, P respiratory distress syndrome (HR = 2.3; P = .02) predicted patients most likely to die. The Acute Physiology and Chronic Health Evaluation II score was not a significant predictor of outcome when either model included the simpler McCabe and Jackson classification of underlying disease severity. We compared the health status scores with norms for the general population and found that patients with resolved sepsis reported more physical dysfunction (P bedridden), suggesting that the patients' physical function

  11. A hands-on approach for fitting long-term survival models under the GAMLSS framework.

    Science.gov (United States)

    de Castro, Mário; Cancho, Vicente G; Rodrigues, Josemar

    2010-02-01

    In many data sets from clinical studies there are patients insusceptible to the occurrence of the event of interest. Survival models which ignore this fact are generally inadequate. The main goal of this paper is to describe an application of the generalized additive models for location, scale, and shape (GAMLSS) framework to the fitting of long-term survival models. In this work the number of competing causes of the event of interest follows the negative binomial distribution. In this way, some well known models found in the literature are characterized as particular cases of our proposal. The model is conveniently parameterized in terms of the cured fraction, which is then linked to covariates. We explore the use of the gamlss package in R as a powerful tool for inference in long-term survival models. The procedure is illustrated with a numerical example. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  12. Long-term survival from gastrocolic fistula secondary to adenocarcinoma of the transverse colon

    Directory of Open Access Journals (Sweden)

    Murali Kothandaraman

    2005-02-01

    Full Text Available Abstract Background Gastrocolic fistula is a rare presentation of both benign and malignant diseases of the gastrointestinal tract. Malignant gastrocolic fistula is most commonly associated with adenocarcinoma of the transverse colon in the Western World. Despite radical approaches to treatment, long-term survival is rarely documented. Case presentation We report a case of a 24-year-old woman who presented with the classic triad of symptoms associated with gastrocolic fistula. Radical en-bloc surgery and adjuvant chemotherapy were performed. She is still alive ten years after treatment. Conclusions Gastrocolic fistula is an uncommon presentation of adenocarcinoma of the transverse colon. Radical en-bloc surgery with adjuvant chemotherapy may occasionally produce long-term survival.

  13. Long-term survival in nasopharyngeal carcinoma and late complications of irradiation

    International Nuclear Information System (INIS)

    Furukawa, Mitsuru; Komori, Takashi; Ishiguro, Hideyo; Takimoto, Toru; Umeda, Ryozo

    1983-01-01

    Irradiation remains the mainstay of treatment of nasopharyngeal carcinoma in the primary site and the neck. We studied the long-term effects of irradiation in five patients who have survived ten or more years after treatment without recurrence of disease, and we were impressed by the rarity of disabling complications of the treatment. Minor complications were common, and especially troublesome were xerostomia, dental caries, postnasal crusting and neck weakness. (author)

  14. Long-term effects of edaravone on survival of patients with amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Masamitsu Okada

    2018-06-01

    Full Text Available Background and purpose: Oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS. Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients. Methods: We retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016. Results: The differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients. Conclusion: Our retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS. Keywords: Amyotrophic lateral sclerosis, Oxidative stress, Edaravone, Long-term effect, Survival

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

    International Nuclear Information System (INIS)

    Malzoni, Carlos Eduardo

    1996-01-01

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

  16. Does tumour location influence postoperative long-term survival in patients with oesophageal squamous cell carcinoma?

    Science.gov (United States)

    Shi, Hui; Zhang, Kun; Niu, Zhong-Xi; Wang, Wen-Ping; Gao, Qiang; Chen, Long-Qi

    2015-08-01

    The seventh edition of the American Joint Committee on Cancer (AJCC) staging system introduced tumour location for the first time as an determinant of stage grouping in pathological T2N0M0 and T3N0M0 (pT2-3N0M0) oesophageal squamous cell carcinoma (OSCC). However, the new modification remains controversial. The objective of this study was to investigate the correlation between tumour location and postoperative long-term survival in patients with OSCC in China. The clinicopathological data and over 10 years of follow-up results from a large cohort of 988 patients with OSCC undergoing radical-intent oesophagectomy from 1984 to 1995 without preoperative and postoperative chemoradiotherapy were reviewed, in which 632 patients were staged as pT2-3N0M0. Tumour location was redefined according to the seventh edition of the AJCC staging system. Survival was calculated by the Kaplan-Meier method; univariate log-rank and multivariate Cox proportional hazard models were used to further determine the impact of tumour location on long-term survival. Univariate analysis showed that OSCC tumour location was closely associated with long-term survival for the entire cohort of 988 patients (odds ratio [OR]: 0.82; 95% confidence interval [95% CI]: 0.67-0.99; P = 0.049), and for pT2-3N0M0 patients (OR: 0.63; 95% CI: 0.48-0.84; P = 0.001). The median survival times for patients with pT2-3N0M0 OSCC in the upper, middle and lower third of the oesophagus were 38.1, 46.6 and 66.0 months, respectively, with corresponding 5-year survival rates of 40.0, 51.8 and 66.2%, respectively. Overall survival rates among three categories of patients according to tumour location in the pT2-3N0M0 patients were statistically different (P = 0.004). Multivariate analysis demonstrated that tumour location was a significant independent predictor of long-term survival for pT2-3N0M0 patients (OR: 0.53; 95% CI: 0.42-0.67; P = 0.0001), but not for the entire cohort of 988 patients (OR: 0.99; 95% CI: 0.79-1.23; P

  17. Long-term monitoring of Sacramento Shade program trees: tree survival, growth and energy-saving performance

    Science.gov (United States)

    Yekang Ko; Jun-Hak Lee; E. Gregory McPherson; Lara A. Roman

    2015-01-01

    Long-term survival and growth of urban forests are critical to achieve the targeted benefits of urban tree planting programs, such as building energy savings from tree shade. However, little is known about how trees perform in the long-term, especially in residential areas. Given this gap in the literature, we monitored 22-years of post-planting survival, growth, and...

  18. Biochemical Mechanisms and Energy Strategies of Geobacter sulfurreducens for Long- Term Survival

    Science.gov (United States)

    Helmus, R. A.; Liermann, L. J.; Brantley, S. L.; Tien, M.

    2008-12-01

    Numerous species of bacteria have been observed to exhibit a growth advantage in stationary phase (GASP) phenotype, indicating that microorganisms starved of an energy source may adapt to allow for long-term survival. Understanding how Geobacter sulfurreducens persists using various metal forms as energy sources and whether a GASP phenotype develops during long-term growth are important for efficient application of this bacterium to sites requiring engineered bioremediation of soluble metals. Thus, we investigated the growth kinetics and survival of G. sulfurreducens. The growth rate of G. sulfurreducens was highest when cultured with soluble iron and generally higher on iron oxide than manganese oxide, suggesting that soluble metal forms are more readily utilized as energy sources by G. sulfurreducens. By monitoring the abundance of G. sulfurreducens in batch cultures for >6 months, distinct growth, stationary, and prolonged starvation phases were observed and a cell density of 105- 106 cells/mL persisted under long-term starvation conditions. The outgrowth of an aged G. sulfurreducens strain co-cultured with a young strain was monitored as a measure of the existence of the GASP phenotype. As the strains aged, the rpoS gene was cloned and sequenced at different stages of growth to identify mutations corresponding to a growth advantage. The results of these studies provide insight into the use of various metal forms for growth by G. sulfurreducens and its ability to persist when starved of energy sources.

  19. Long-term graft and patient survival following renal transplantation in diabetic patients

    DEFF Research Database (Denmark)

    Rømming Sørensen, Vibeke; Schwartz Sørensen, Søren; Feldt-Rasmussen, Bo

    2006-01-01

    . The groups were similar with respect to age and sex. RESULTS: The patient survival rates (diabetic versus non-diabetic patients) were 88% vs 91% (p=NS) at 1 year, 68% vs 73% (p=NS) at 5 years and 31% vs 52% (pnon-diabetic patients) were 72% vs 72...... patients, 55% were smokers. Among the diabetic patients, graft and patient survival were independent of smoking habits, blood pressure, HbA1c and total cholesterol. CONCLUSIONS: Graft survival was similar in diabetic and non-diabetic patients. For the first 5 years following renal transplantation......OBJECTIVE: To study long-term graft and patient survival following renal transplantation in diabetic and non-diabetic patients. MATERIAL AND METHODS: Over the time period 1985-99, 498 transplantations in 399 non-diabetic patients and 68 transplantations in 62 diabetic patients were performed...

  20. Conditional long-term survival following minimally invasive robotic mitral valve repair: a health services perspective.

    Science.gov (United States)

    Efird, Jimmy T; Griffin, William F; Gudimella, Preeti; O'Neal, Wesley T; Davies, Stephen W; Crane, Patricia B; Anderson, Ethan J; Kindell, Linda C; Landrine, Hope; O'Neal, Jason B; Alwair, Hazaim; Kypson, Alan P; Nifong, Wiley L; Chitwood, W Randolph

    2015-09-01

    Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to compute conditional survival in patients who received a robotically assisted, minimally invasive mitral valve repair procedure (RMVP). Patients who received RMVP with annuloplasty band from May 2000 through April 2011 were included. A 5- and 10-year conditional survival model was computed using a multivariable product-limit method. Non-smoking men (≤65 years) who presented in sinus rhythm had a 96% probability of surviving at least 10 years if they survived their first year following surgery. In contrast, recent female smokers (>65 years) with preoperative atrial fibrillation only had an 11% probability of surviving beyond 10 years if alive after one year post-surgery. In the context of an increasingly managed healthcare environment, conditional survival provides useful information for patients needing to make important treatment decisions, physicians seeking to select patients most likely to benefit long-term following RMVP, and hospital administrators needing to comparatively assess the life-course economic value of high-tech surgical procedures.

  1. Prognostic Factors Affecting Long-Term Survival after Resection for Noncolorectal, Nonneuroendocrine, and Nonsarcoma Liver Metastases

    Directory of Open Access Journals (Sweden)

    Fabio Uggeri

    2017-01-01

    Full Text Available Aim. To evaluate feasibility and long-term outcome after hepatic resection for noncolorectal, nonneuroendocrine, and nonsarcoma (NCNNNS liver metastases in a single center. Methods. We retrospectively reviewed our experience on patients who underwent surgery for NCNNNS liver metastases from 1995 to 2015. Patient baseline characteristics, tumor features, treatment options, and postoperative outcome were retrieved. Results. We included 47 patients. The overall 5-year survival (OS rate after hepatectomy was 27.6%, with a median survival of 21 months. Overall survival was significantly longer for patients operated for nongastrointestinal liver metastases when compared with gastrointestinal (41 versus 10 months; p=0.027. OS was significantly worse in patients with synchronous metastases than in those with metachronous disease (10 versus 22 months; p=0.021. The occurrence of major postoperative complication negatively affected long-term prognosis (OS 23.5 versus 9.0 months; p=0.028. Preoperative tumor characteristics (number and size of the lesions, intraoperative features (extension of resection, need for transfusions, and Pringle’s maneuver, and R0 at pathology were not associated with differences in overall survival. Conclusion. Liver resection represents a possible curative option for patients with NCNNNS metastases. The origin of the primary tumor and the timing of metastases presentation may help clinicians to better select which patients could take advantages from surgical intervention.

  2. Impact of diabetes on treatment outcomes and long-term survival in multidrug-resistant tuberculosis.

    Science.gov (United States)

    Kang, Young Ae; Kim, Song Yee; Jo, Kyung-Wook; Kim, Hee Jin; Park, Seung-Kyu; Kim, Tae-Hyung; Kim, Eun Kyung; Lee, Ki Man; Lee, Sung Soon; Park, Jae Seuk; Koh, Won-Jung; Kim, Dae Yun; Shim, Tae Sun

    2013-01-01

    Few studies have investigated the impact of diabetes mellitus (DM), a globally increasing metabolic disease, on treatment outcomes and long-term survival in patients with multidrug-resistant forms of tuberculosis (MDR-TB). We analyzed outcomes in a large cohort to assess the impact of DM on treatment outcomes of patients with MDR-TB. MDR-TB patients newly diagnosed or retreated between 2000 and 2002 and followed for 8-11 years were retrospectively analyzed with respect to the effect of DM as a comorbidity on their treatment outcome and long-term survival. Of 1,407 patients with MDR-TB, 239 (17.0%) had coexisting DM. The mean age and body mass index were higher in MDR-TB patients with DM [MDR-TBDM(+)] than in those without DM [MDR-TBDM(-)]. Patients with MDR-TB and a comorbidity of DM had a significantly lower treatment success rate than those without a history of DM (36.0 vs. 47.2%, p = 0.002). In addition, DM was the negative predictor for MDR-TB treatment success in multivariate analyses [odds ratio 0.51, 95% confidence interval (CI) 0.26-0.99]. Mean survival times were also lower in MDR-TBDM(+) than in MDR-TBDM(-) patients (102 vs. 114 months, p = 0.001), with DM as a significant predictor of poor long-term survival in multivariate analyses (hazard ratio 1.59, 95% CI 1.01-2.50). Among MDR-TB patients, DM was a relatively common comorbidity. In patients undergoing treatment for MDR-TB and followed for 8-11 years, it was found to be independently associated with an increased risk of both treatment failure and death. Copyright © 2013 S. Karger AG, Basel.

  3. Preoperative White Matter Lesions Are Independent Predictors of Long-Term Survival after Internal Carotid Endarterectomy

    Directory of Open Access Journals (Sweden)

    Niku Oksala

    2014-06-01

    Full Text Available Background: Cerebral white matter lesions (WMLs predict long-term survival of conservatively treated acute stroke patients with etiology other than carotid stenosis. In carotid endarterectomy patients, WMLs are associated with severe carotid stenosis and unstable plaques, with the risk of perioperative complications and with increased 30-day perioperative risk of death. However, no data exist on their effect on postoperative long-term survival, a factor important when considering the net benefit from carotid endarterectomy. Whether this effect is independent of classical risk factors and indications for surgery is not known either. We hypothesized that WMLs could be evaluated from preoperative routine computed tomography (CT scans and are predictors of postoperative survival, independent of classical cardiovascular risk factors, indication category and degree of carotid stenosis. Methods: A total of 353 of 481 (73.4% consecutive patients subjected to carotid endarterectomy due to different indications, i.e. asymptomatic stenosis (n = 28, 7.9%, amaurosis fugax (n = 52, 14.7%, transient ischemic attack (n = 135, 38.2% or ischemic stroke (n = 138, 39.1%, from prospective vascular registries during the years 2001-2010 with digital preoperative CT scans, were included in the study. WMLs were rated by a radiologist (Wahlund criteria in a blinded fashion. Internal carotid artery (ICA stenoses were angiographically graded (Results: WML severity could be assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p Conclusions: WMLs in a preoperative CT scan provide a substantially reliable estimate of postoperative long-term survival of carotid endarterectomy patients independent of currently used criteria, i.e. cardiovascular risk factors, indication category and degree of ipsilateral ICA stenosis.

  4. Chemotherapy increases long-term survival in patients with adult medulloblastoma

    DEFF Research Database (Denmark)

    Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

    2016-01-01

    chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo...... parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. METHODS: We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification......)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. CONCLUSIONS: This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival...

  5. Prognostic factors for progression-free and overall survival in advanced biliary tract cancer

    DEFF Research Database (Denmark)

    Bridgewater, J; Lopes, A; Wasan, H

    2016-01-01

    independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression......BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable...... biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict...

  6. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.

    Science.gov (United States)

    Topalian, Suzanne L; Sznol, Mario; McDermott, David F; Kluger, Harriet M; Carvajal, Richard D; Sharfman, William H; Brahmer, Julie R; Lawrence, Donald P; Atkins, Michael B; Powderly, John D; Leming, Philip D; Lipson, Evan J; Puzanov, Igor; Smith, David C; Taube, Janis M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; Pardoll, Drew M; Sosman, Jeffrey A; Hodi, F Stephen

    2014-04-01

    Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

  7. Long-term survival in an adolescent with widely metastatic renal cell carcinoma with rhabdoid features.

    Science.gov (United States)

    Ettinger, L J; Goodell, L A; Javidian, P; Hsieh, Y; Amenta, P

    2000-01-01

    Renal cell carcinoma is rarely seen in children and adolescents. Patients with widespread disease at diagnosis have a particularly poor survival rate. Currently, all known chemotherapy has been ineffective in improving the median survival in patients with advanced disease. A 13-year-old black boy with stage IV renal cell carcinoma with rhabdoid features is a long-term disease-free survivor after aggressive multiagent chemotherapy. After the initial evaluation and histologic diagnosis of renal cell carcinoma, the patient received three courses of an aggressive chemotherapy regimen consisting of vincristine, doxorubicin, cyclophosphamide with mesna uroprotection, granulocyte colony-stimulating factor and erythropoietin (Epogen). After an almost complete response, a radical nephrectomy was performed and results demonstrated a solitary small nodule with viable tumor. After surgery, he received floxuridine infusion for 14 days by circadian schedule at 28-day intervals for a total of 1 year. The patient is well and free of disease 5 years after initial presentation. The dramatic response to treatment and long-term disease-free survival of this patient suggest this chemotherapeutic approach warrants additional investigation.

  8. Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hisao Imai

    2015-01-01

    Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

  9. Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT).

    Science.gov (United States)

    Wong, Anthony C; Watson, Sydeaka P; Pitroda, Sean P; Son, Christina H; Das, Lauren C; Stack, Melinda E; Uppal, Abhineet; Oshima, Go; Khodarev, Nikolai N; Salama, Joseph K; Weichselbaum, Ralph R; Chmura, Steven J

    2016-07-15

    The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases. Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS. Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available. A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242-50. © 2016 American Cancer Society. © 2016 American Cancer Society.

  10. Antioxidant defenses predict long-term survival in a passerine bird.

    Directory of Open Access Journals (Sweden)

    Nicola Saino

    2011-05-01

    Full Text Available Normal and pathological processes entail the production of oxidative substances that can damage biological molecules and harm physiological functions. Organisms have evolved complex mechanisms of antioxidant defense, and any imbalance between oxidative challenge and antioxidant protection can depress fitness components and accelerate senescence. While the role of oxidative stress in pathogenesis and aging has been studied intensively in humans and model animal species under laboratory conditions, there is a dearth of knowledge on its role in shaping life-histories of animals under natural selection regimes. Yet, given the pervasive nature and likely fitness consequences of oxidative damage, it can be expected that the need to secure efficient antioxidant protection is powerful in molding the evolutionary ecology of animals. Here, we test whether overall antioxidant defense varies with age and predicts long-term survival, using a wild population of a migratory passerine bird, the barn swallow (Hirundo rustica, as a model.Plasma antioxidant capacity (AOC of breeding individuals was measured using standard protocols and annual survival was monitored over five years (2006-2010 on a large sample of selection episodes. AOC did not covary with age in longitudinal analyses after discounting the effect of selection. AOC positively predicted annual survival independently of sex. Individuals were highly consistent in their relative levels of AOC, implying the existence of additive genetic variance and/or environmental (including early maternal components consistently acting through their lives.Using longitudinal data we showed that high levels of antioxidant protection positively predict long-term survival in a wild animal population. Present results are therefore novel in disclosing a role for antioxidant protection in determining survival under natural conditions, strongly demanding for more longitudinal eco-physiological studies of life-histories in

  11. Long-Term Survival in Young Women: Hazards and Competing Risks after Thyroid Cancer

    International Nuclear Information System (INIS)

    Stroup, A. M.; Harrell, C. J.; Herget, K. A.

    2012-01-01

    Differentiated thyroid cancers (DTCs) are one of the most common and survivable cancers diagnosed in women. We examine factors associated with long-term survival and competing risks of death in women diagnosed with DTC under the age of 40 (<40) and aged 40 and older (40+). Methods. SEER data was used to identify DTCs diagnosed in women from 1975 to 2009. We examined overall (OS), disease-specific (DSS), other cancer (OCS), and non-cancer-related (NCS) survival using multivariate Cox proportional hazards modeling. Results. Observed survival was 97.2% for <40 (n=14,540) and 82.5% for 40+ (n=20,513). Distant stage (HR=1.96, 95% CI 1.23-3.07), non-Hispanic Black (HR=2.04, 95% CI 1.45-2.87), being unmarried (HR=1.26, 95% 1.03-1.54), and subsequent primary cancers (HR=4.63, 95% CI 3.76-5.71) were significant for OS in women <40. Age was an effect modifier for all survival outcomes. Racial disparities in NCS were most pronounced for young non-Hispanic black women (HR=3.36, 95% CI 2.17-5.22). Women in both age groups were more likely to die from other causes. Conclusions. Age at diagnosis remains one of the strongest prognostic factors for thyroid cancer survival. More directed efforts to ensure effective care for co morbid conditions are needed to reduce mortality from other causes.

  12. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

    Science.gov (United States)

    Yardley, Denise A; Noguchi, Shinzaburo; Pritchard, Kathleen I; Burris, Howard A; Baselga, José; Gnant, Michael; Hortobagyi, Gabriel N; Campone, Mario; Pistilli, Barbara; Piccart, Martine; Melichar, Bohuslav; Petrakova, Katarina; Arena, Francis P; Erdkamp, Frans; Harb, Wael A; Feng, Wentao; Cahana, Ayelet; Taran, Tetiana; Lebwohl, David; Rugo, Hope S

    2013-10-01

    Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

  13. Long-term effects of edaravone on survival of patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Okada, Masamitsu; Yamashita, Satoshi; Ueyama, Hidetsugu; Ishizaki, Masatoshi; Maeda, Yasushi; Ando, Yukio

    2018-06-01

    Oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients. We retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016. The differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients. Our retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS.

  14. Biologically-equivalent dose and long-term survival time in radiation treatments

    International Nuclear Information System (INIS)

    Zaider, Marco; Hanin, Leonid

    2007-01-01

    Within the linear-quadratic model the biologically-effective dose (BED)-taken to represent treatments with an equal tumor control probability (TCP)-is commonly (and plausibly) calculated according to BED(D) = -log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, T eff . By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between T eff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than T eff ) may result in a miscalculation (underestimation) of the initial number of clonogens

  15. Long-term survival of an urban fruit bat seropositive for Ebola and Lagos bat viruses.

    Directory of Open Access Journals (Sweden)

    David T S Hayman

    2010-08-01

    Full Text Available Ebolaviruses (EBOV (family Filoviridae cause viral hemorrhagic fevers in humans and non-human primates when they spill over from their wildlife reservoir hosts with case fatality rates of up to 90%. Fruit bats may act as reservoirs of the Filoviridae. The migratory fruit bat, Eidolon helvum, is common across sub-Saharan Africa and lives in large colonies, often situated in cities. We screened sera from 262 E. helvum using indirect fluorescent tests for antibodies against EBOV subtype Zaire. We detected a seropositive bat from Accra, Ghana, and confirmed this using western blot analysis. The bat was also seropositive for Lagos bat virus, a Lyssavirus, by virus neutralization test. The bat was fitted with a radio transmitter and was last detected in Accra 13 months after release post-sampling, demonstrating long-term survival. Antibodies to filoviruses have not been previously demonstrated in E. helvum. Radio-telemetry data demonstrates long-term survival of an individual bat following exposure to viruses of families that can be highly pathogenic to other mammal species. Because E. helvum typically lives in large urban colonies and is a source of bushmeat in some regions, further studies should determine if this species forms a reservoir for EBOV from which spillover infections into the human population may occur.

  16. Long-term kinetics of Salmonella Typhimurium ATCC 14028 survival on peanuts and peanut confectionery products.

    Directory of Open Access Journals (Sweden)

    Maristela S Nascimento

    Full Text Available Due to recent large outbreaks, peanuts have been considered a product of potential risk for Salmonella. Usually, peanut products show a low water activity (aw and high fat content, which contribute to increasing the thermal resistance and survival of Salmonella. This study evaluated the long-term kinetics of Salmonella survival on different peanut products under storage at 28°C for 420 days. Samples of raw in-shell peanuts (aw = 0.29, roasted peanuts (aw = 0.39, unblanched peanut kernel (aw = 0.54, peanut brittle (aw = 0.30, paçoca (aw = 0.40 and pé-de-moça (aw = 0.68 were inoculated with Salmonella Typhimurium ATCC 14028 at two inoculum levels (3 and 6 log cfu/ g. The Salmonella behavior was influenced (p420 days, especially in products with aw around 0.40.

  17. Conventional chemotherapy and long-term survival in multiple myeloma patients

    International Nuclear Information System (INIS)

    Kraj, M; Poglod, R.; Sokolowska, U.; Kruk, B.; Maj, S.

    2010-01-01

    Objectives. The study was especially focused on the estimation of real frequency of long-term survivals in patients with multiple myeloma and finding common clinical and laboratory features present in long-term surviving patients as possible good prognostic factors. Material and methods. The survey was carried out on 600 multiple myeloma patients diagnosed before the year 2000 and treated with conventional chemotherapy in the Institute of Hematology and Transfusion Medicine in Warsaw in the years 1962-2009. All patients who had fulfilled the requirement of more than seven years of survival from the diagnosis and beginning of treatment for myeloma were included into the study group. Results. Out of 600 studied patients with multiple myeloma 88 (14.7%) survived over 7 years including 45 (7.5%) over 10 years, 11 (1.8 %) over 15 years and 7 (1.1%) over 20 years from the disease diagnosis and beginning of antitumor treatment. Patients with long survival were younger (median age 55 years) at the time of diagnosis than the whole studied group and had normal serum creatinine, calcium and beta2-microglobulin levels. Sixty eight percent of these patients had stage I or II clinical progression, 60% presented with IgG monoclonal protein and 58% with osteolysis. Treatment with melphalan only was given to 18 patients, 30 were treated with melphalan, followed by vincristine, cyclophosphamide, BCNU, doxorubicin and prednisone or dexamethasone. Polychemotherapy was given from the time of the diagnosis to 16 patients, 15 received radiotherapy or 60C o irradiation besides chemotherapy and 9 received new agents: thalidomide, bortezomib, lenalidomide. In 66% of the evaluated cases response to treatment was good and in another 34% stabilization of the proliferative process was achieved. The mean duration of treatment till the achievement of partial response was 10 months, range: 2 - 89 months. The mean duration of good therapeutic response was 70 months. Twelve patients are alive and

  18. Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Ottosen, Tobias Pilgaard; Grijota, Miriam; Hansen, Morten Lock

    2016-01-01

    inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality......BACKGROUND AND PURPOSE: The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage...... and examined the impact of subsequent AT use on the long-term clinical outcome. METHODS: We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were...

  19. Contrasting long-term survival of two outplanted Mojave Desert perennials for post-fire revegetation

    Science.gov (United States)

    Scoles-Sciulla, Sara J.; Defalco, Lesley A.; Esque, Todd C.

    2015-01-01

    Post-fire recovery of arid shrublands is typically slow, and planting greenhouse-raised seedlings may be a means of jump-starting this process. Recovery can be further accelerated by understanding the factors controlling post-planting survival. In fall 2007 and 2009, we outplanted seedlings of two contrasting native evergreen shrubs—fast-growing Nevada jointfir and slow-growing blackbrush—across five burned sites in the Mojave Desert. To increase soil moisture and optimize seedling survival, we experimentally applied and evaluated soil amendments and supplemental watering. We also evaluated two herbicides that reduce competitive invasive annual grasses and two types of herbivore protection. Survival of jointfir outplanted in 2007 was 61% after 43 months, and site largely influenced survival, while herbicide containing imazapic applied more than one year after outplanting reduced survival. Reduced survival of jointfir outplanted in 2009 coincided with delayed seasonal precipitation that intensified foliar damage by small mammals. In contrast, blackbrush survival was 4% after 43 months, and was influenced by site, type of herbivore protection, and greenhouse during the 2007 outplanting, and soil amendment during 2009. Counter to expectations, we found that supplemental watering and soil amendments did not influence long-term survival of either blackbrush or jointfir. Shrub species with rapid growth rates and broad environmental tolerances, such as jointfir, make ideal candidates for outplanting, provided that seedlings are protected from herbivores. Re-introduction of species with slow growth rates and narrow environmental tolerances, such as blackbrush, requires careful consideration to optimize pre- and post-planting conditions.

  20. Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives.

    Science.gov (United States)

    Durando, Xavier; Thivat, Emilie; D'Incan, Michel; Sinsard, Anne; Madelmont, Jean-Claude; Chollet, Philippe

    2005-11-15

    Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of approximately 6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase Cystemustine efficiency.

  1. Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives

    Directory of Open Access Journals (Sweden)

    Sinsard Anne

    2005-11-01

    Full Text Available Abstract Background Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU (60 or 90 mg/m2. Case presentation We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Conclusion Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency.

  2. PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

    Science.gov (United States)

    Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

    2018-03-01

    To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

  3. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

  4. A thermal control system for long-term survival of scientific instruments on lunar surface.

    Science.gov (United States)

    Ogawa, K; Iijima, Y; Sakatani, N; Otake, H; Tanaka, S

    2014-03-01

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime -200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a "regolith mound". Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  5. A thermal control system for long-term survival of scientific instruments on lunar surface

    International Nuclear Information System (INIS)

    Ogawa, K.; Iijima, Y.; Tanaka, S.; Sakatani, N.; Otake, H.

    2014-01-01

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime −200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a “regolith mound”. Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system

  6. A thermal control system for long-term survival of scientific instruments on lunar surface

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, K., E-mail: ogawa@astrobio.k.u-tokyo.ac.jp [Department of Complexity Science and Engineering, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba (Japan); Iijima, Y.; Tanaka, S. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo, Sagamihara, Kanagawa (Japan); Sakatani, N. [The Graduate University for Advanced Studies, Shonan Village, Hayama, Kanagawa (Japan); Otake, H. [JAXA Space Exploration Center, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo, Sagamihara, Kanagawa (Japan)

    2014-03-15

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime −200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a “regolith mound”. Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  7. Brain tumors in children: long-term survival after radiation treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jenkin, Derek; Greenberg, Mark; Hoffman, Harold; Hendrick, Bruce; Humphreys, Robin; Vatter, Annette

    1995-02-01

    Purpose: To determine the cause of death in children who survive more than 5 years after radiation treatment of a brain tumor. Methods and Material: Nine hundred and twelve consecutive children with a primary brain tumor irradiated at the Princess Margaret Hospital or Toronto-Bayview Regional Cancer Center from 1958 to 1991, were evaluated for long-term outcome. Results: Overall 10- and 20-year survival rates were 44% and 37%. Subsequent survival of 377 5-year survivors was, at an additional 10 and 20 years, 78% and 67%. Most (83%) deaths that occurred more than 5 years from diagnosis were a result of relapse of the original tumor. The 10-year survival rate subsequent to relapse was 9% when the first relapse occurred less than one year from diagnosis, 17% for 1-2 years, and 31% when the time to relapse was 3 years or greater. The cumulative actuarial incidence of, and death from, second malignant tumors at 30 years from diagnosis was 18% and 13%, respectively. Conclusions: Death later than 5 years from diagnosis of a brain tumor in children is common and is usually due to progressive disease in slowly evolving low grade tumors. Death from a second malignant tumor becomes more frequent than death from the original tumor after 15 years from diagnosis.

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  9. Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival

    Directory of Open Access Journals (Sweden)

    Fang Gang

    2008-09-01

    Full Text Available Abstract Background We have engaged in an international program designated the Bank On A Cure, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma. We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, n = 70 versus long term progression-free survivors (greater than 3 years, n = 73 in two phase III clinical trials. Results Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival. While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes. Conclusion A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma. The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS.

  10. A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment

    International Nuclear Information System (INIS)

    Gonçalves, Anthony; Turrini, Olivier; Lelong, Bernard; Viens, Patrice; Borg, Jean-Paul; Birnbaum, Daniel; Olschwang, Sylviane; Viret, Frédéric; Esteyries, Séverine; Taylor-Smedra, Brynn; Lagarde, Arnaud; Ayadi, Mounay; Monges, Geneviève; Bertucci, François; Esterni, Benjamin; Delpero, Jean-Robert

    2008-01-01

    Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity. We analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced. Nine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients. This preliminary study suggests that: an increase in EGFR copy number may be associated with cetuximab response but is a rare event in CRC, KRAS mutations are associated with low response rate but do not preclude any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may predict for cetuximab benefit

  11. Predicting long-term risk for relationship dissolution using nonparametric conditional survival trees.

    Science.gov (United States)

    Kliem, Sören; Weusthoff, Sarah; Hahlweg, Kurt; Baucom, Katherine J W; Baucom, Brian R

    2015-12-01

    Identifying risk factors for divorce or separation is an important step in the prevention of negative individual outcomes and societal costs associated with relationship dissolution. Programs that aim to prevent relationship distress and dissolution typically focus on changing processes that occur during couple conflict, although the predictive ability of conflict-specific variables has not been examined in the context of other factors related to relationship dissolution. The authors examine whether emotional responding and communication during couple conflict predict relationship dissolution after controlling for overall relationship quality and individual well-being. Using nonparametric conditional survival trees, the study at hand simultaneously examined the predictive abilities of physiological (systolic and diastolic blood pressure, heart rate, cortisol) and behavioral (fundamental frequency; f0) indices of emotional responding, as well as observationally coded positive and negative communication behavior, on long-term relationship stability after controlling for relationship satisfaction and symptoms of depression. One hundred thirty-six spouses were assessed after participating in a randomized clinical trial of a relationship distress prevention program as well as 11 years thereafter; 32.5% of the couples' relationships had dissolved by follow up. For men, the only significant predictor of relationship dissolution was cortisol change score (p = .012). For women, only f0 range was a significant predictor of relationship dissolution (p = .034). These findings highlight the importance of emotional responding during couple conflict for long-term relationship stability. (c) 2015 APA, all rights reserved).

  12. Long-term survival in inoperable squamous cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Ono, Ryosuke; Egawa, Sunao

    1988-01-01

    Radiotherapy is the first treatment of choice in cases of inoperable lung cancer. This paper reported the indications and limitations of radiotherapy for squamous cell carcinoma of the lung, based on the results of long-term survivors among non-resected squamous cell carcinoma. Materials consisted of 372 cases of squamous cell carcinoma of the lung treated with radiotherapy at the National Cancer Center Hospital between May 1962 and December 1980. Histopathological diagnosis was confirmed by biopsy in all cases. Among the 372 cases, 8 survived more than 5 years. Analyzing these 8 cases according to the TNM classification of the UICC, 7 were stage I, 1 was stage II, and there were no long-term survivors with stage III or IV. Of the 8 cases only one is alive. Analyzing 7 the fatal cases, 2 succumbed due to hepatic or brain metatasis following local recurrence and one had double primary cancer of the pancreas. The remaining 4 cases did not show recurrence or metastasis and succumbed due to pneumonia or myocardial infarct. (author)

  13. Long-term survival and healthcare utilization outcomes attributable to sepsis and pneumonia

    Directory of Open Access Journals (Sweden)

    Dick Andrew

    2012-11-01

    Full Text Available Abstract Background Hospital associated infections are major problems, which are increasing in incidence and very costly. However, most research has focused only on measuring consequences associated with the initial hospitalization. We explored the long-term consequences of infections in elderly Medicare patients admitted to an intensive care unit (ICU and discharged alive, focusing on: sepsis, pneumonia, central-line-associated bloodstream infections (CLABSI, and ventilator-associated pneumonia (VAP; the relationships between the infections and long-term survival and resource utilization; and how resource utilization was related to impending death during the follow up period. Methods Clinical data and one year pre- and five years post-index hospitalization Medicare records were examined. Hazard ratios (HR and healthcare utilization incidence ratios (IR were estimated from state of the art econometric models. Patient demographics (i.e., age, gender, race and health status and Medicaid status (i.e., dual eligibility were controlled for in these models. Results In 17,537 patients, there were 1,062 sepsis, 1,802 pneumonia, 42 CLABSI and 52 VAP cases. These subjects accounted for 62,554 person-years post discharge. The sepsis and CLABSI cohorts were similar as were the pneumonia and VAP cohorts. Infection was associated with increased mortality (sepsis HR = 1.39, P  Conclusions The infections had significant and lasting adverse consequences among the elderly. Yet, many of these infections may be preventable. Investments in infection prevention interventions are needed in both community and hospitals settings.

  14. Long-term survival in acute leukemia in Japan. A study of 304 cases.

    Science.gov (United States)

    Kawashima, K; Suzuki, H; Yamada, K; Kato, Y; Watanabe, E; Morishima, Y; Takeyama, H; Kobayashi, M

    1980-04-15

    In a national survey of five-year survivors with acute leukemia, 233 of 304 cases were children under 14 years of age and 71 were adults. There were 107 myeloblastic, 10 promyelocytic, 142 lymphocytic, and 37 undifferentiated leukemias, Forty-five cases at age 3 represented the peak. These long-term survivors have shown a yearly increase in number. In 1972, the number of childhood ALL cases reached 38 with no great changes in ANLL cases. With respect to prognosis among long-term survivors, it seemed that neither type of leukemia nor age at diagnosis were factors influencing the future survival. CNS relapse occurring before the third year was an unfavorable complication for a prognosis beyond five years. Only 8 patients died of leukemia among 155 patients who reached five years in their initial complete remission; 49 of 90 patients who had relapse within five years after diagnosis died of leukemia. From these findings, it seems very important to follow patients for five years in their initial complete remission.

  15. Functional Gain After Inpatient Stroke Rehabilitation: Correlates and Impact on Long-Term Survival.

    Science.gov (United States)

    Scrutinio, Domenico; Monitillo, Vincenzo; Guida, Pietro; Nardulli, Roberto; Multari, Vincenzo; Monitillo, Francesco; Calabrese, Gianluigi; Fiore, Pietro

    2015-10-01

    Prediction of functional outcome after stroke rehabilitation (SR) is a growing field of interest. The association between SR and survival still remains elusive. We sought to investigate the factors associated with functional outcome after SR and whether the magnitude of functional improvement achieved with rehabilitation is associated with long-term mortality risk. The study population consisted of 722 patients admitted for SR within 90 days of stroke onset, with an admission functional independence measure (FIM) score of stroke onset to rehabilitation admission (PStroke Scale score at rehabilitation admission (P<0.001), and aphasia (P=0.021) were independently associated with FIM gain. The R2 of the model was 0.275. During a median follow-up of 6.17 years, 36.9% of the patients died. At multivariable Cox analysis, age (P<0.0001), coronary heart disease (P=0.018), atrial fibrillation (P=0.042), total cholesterol (P=0.015), and total FIM gain (P<0.0001) were independently associated with mortality. The adjusted hazard ratio for death significantly decreased across tertiles of increasing FIM gain. Several factors are independently associated with functional gain after SR. Our findings strongly suggest that the magnitude of functional improvement is a powerful predictor of long-term mortality in patients admitted for SR. © 2015 American Heart Association, Inc.

  16. Long term survival with the combination of interferon and chemotherapy in metastatic melanoma

    International Nuclear Information System (INIS)

    Karagoz, B.; Bilgi, O.; Ozgun, A.; Emirzeoglu, L.; Celika, S.; Ozet, A.

    2015-01-01

    The prognosis of metastatic melanoma is poor. Pre-targeted treatment era, the combination of interferon-α (IF-α) plus chemotherapy had been used and have generally short response duration. Herein, we present a metastatic melanoma case that achieved long-term durable complete response (CR) IF-α plus chemotherapy and IF-α maintenance therapy and had lower Regulatory T (Treg) cells. A fifty-year old woman was admitted to the hospital with metastatic melanoma. Lactate dehydrogenase (LDH) level was 660 U/L. The percentage of CD4+CD25+ Treg cells was 2.4% in CD4+ lymphocytes. The IF-α plus chemotherapy and IF-α maintenance were administered. After six courses of chemotherapy, CR was achieved. Vitiligo and hypothyroidism occurred. The patient has remained in CR for approximately 7 years until second pleural metastases were detected and death. The patient has positive prognostic factors such as induction of auto immunity, small tumor volume, mild elevated LDH level, and lower Treg cell percentage. She survived long term with CR after IF-α treatment with concurrent chemotherapy and maintenance. IF-α plus chemotherapy may be a treatment option for metastatic melanoma in selected cases who cannot reach new targeted drugs

  17. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Baume, Dominique; Lilly, Carrie

    2015-01-01

    Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Cases of long-term survival of ≥3 years’ duration (from diagnosis of metastatic disease) were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Eighteen cases were identified that identified survival of ≥3 years’ duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94%) had survived ≥5 years, and eleven patients (61%) had survived ≥10 years (range: 3–15 years). The median survival duration with metastatic disease was 11 years; 15 remained alive and three had died. Published studies of melanoma therapies were tabled for comparison. The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself

  18. A case of long term survival with skeletal only metastatic breast cancer.

    Science.gov (United States)

    Kuechle, Joseph B; McGrath, Brian E; Khoury, Thaer; Mindell, Eugene R

    2015-01-01

    The prognosis of patients with metastatic breast cancer is very poor. Because of this, treatment of skeletal metastasis is often palliative with limited goals rather than cure. However, there are those patients, such as presented here, who survive for an extended time. This thirty-six year old female presented with lytic lesions to one ulna and rib five years after mastectomy for breast cancer. Despite radiation and chemotherapy, the ulnar lesion expanded and resulted in an elbow dislocation. The rib lesion was resected and the arm amputated above the elbow. She developed local recurrence in both her above elbow amputation stump and chest wall and a more proximal below shoulder amputation was performed with resection of chest wall lesion. Even though she had locally aggressive disease, she has survived for 31 years after diagnosis without any evidence of disease. Reports of metastatic breast cancer survival indicate the five year survival to be 15%. There have been few reports indicating that those patients with skeletal only or oligometastatic disease have improved prognosis. It is not clear what biological properties of these tumors results in the improved survival. This case highlights the challenges of giving patients the optimal treatment in the light of limited ability to predict prognosis. It also highlights the need to further investigate the phenotypes of breast cancer that can, despite metastatic disease and with modern treatment go on to long survival. In addition this case demonstrates the importance of long term followup. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

    Science.gov (United States)

    Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

    2013-05-01

    Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

  20. The prediction of progression-free and overall survival in women with an advanced stage of epithelial ovarian carcinoma.

    Science.gov (United States)

    Gerestein, C G; Eijkemans, M J C; de Jong, D; van der Burg, M E L; Dykgraaf, R H M; Kooi, G S; Baalbergen, A; Burger, C W; Ansink, A C

    2009-02-01

    Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. Retrospective observational study. Two teaching hospitals and one university hospital in the south-western part of the Netherlands. Women with advanced stage EOC. All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. The primary outcome measure was OS and the secondary outcome measures were response and PFS. A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease statistic of 0.67. PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.

  1. Patient function, long-term survival, and use of surgery in patients with kidney cancer.

    Science.gov (United States)

    Tan, Hung-Jui; Chamie, Karim; Daskivich, Timothy J; Litwin, Mark S; Hu, Jim C

    2016-12-15

    Beyond age and comorbidity, functionality can shape the long-term survival potential of patients with cancer. Accordingly, herein the authors compared mortality and receipt of cancer-directed surgery according to patient function among older adults with kidney cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2000 through 2009, the authors studied 28,326 elderly subjects with primary kidney cancer. Patient function was quantified using function-related indicators, claims indicative of dysfunction and disability. Adjusting for patient and cancer characteristics, competing risk regression was used to assess the relationship between function-related indicator count and cause-specific mortality and then generalized estimating equations were used to quantify the probability of surgery. A total of 13,619 adult patients (48.1%) with at least 1 function-related indicator were identified. A higher indicator category was associated with older age, greater comorbidity, female sex, unmarried status, lower socioeconomic status, and higher stage of disease (Pkidney cancer mortality varied minimally with patient function. Patients with ≥ 2 indicators received cancer-directed surgery less often than those without disability (odds ratio, 0.61; 95% CI, 0.56-0.66), although treatment probabilities remained high for patients with locoregional disease and low for those with metastatic cancer. Among older adults with kidney cancer, functional health stands as a significant predictor of long-term survival. However, receipt of cancer-directed surgery appears largely determined by cancer stage. Patient function should be considered more heavily when determining treatment for older adults with kidney cancer. Cancer 2016;122:3776-3784. © 2016 American Cancer Society. © 2016 American Cancer Society.

  2. Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

    Science.gov (United States)

    Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

    2016-04-01

    Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

  3. Effect of donor age on long-term survival following cardiac transplantation.

    Science.gov (United States)

    Topkara, Veli K; Cheema, Faisal H; Kesavaramanujam, Satish; Mercando, Michelle L; Forster, Catherine S; Argenziano, Michael; Esrig, Barry C; Oz, Mehmet C; Naka, Yoshifumi

    2006-01-01

    The current shortage of donor hearts has forced the criteria of organ procurement to be extended, leading to increased use of older donor hearts to bridge the gap between demand and availability. Our objective was to analyze the effect of donor age on outcomes after cardiac transplantation. We retrospectively studied 864 patients who underwent cardiac transplantation at New York Presbyterian Hospital - Columbia University between 1992 and 2002. Patients were divided into two groups; donor age or =40 years (Group B, n = 264). Characteristics including gender, body mass index, and cytomegalovirus (CMV) status were significantly different between the two donor age groups. Race, CMV status, toxoplasmosis status, left ventricular assist device prior to transplant, diabetes mellitus, and retransplantation were similar in both the recipient groups, while age, gender, and BMI were different. Early mortality was lower in Group A, 5%, versus 9.5% in Group B. Multivariate analysis revealed recipient female gender (odd ratio (OR) = 1.71), retransplantation (OR = 1.63), and increased donor age (OR = 1.02) as significant predictors of poor survival in the recipient population. Actuarial survival at 1 year (86.7% vs 81%), 5 years (75% vs 65%), and 10 years (56% vs 42%) was significantly different as well with a log rank p = 0.002. These findings suggest that increased donor age is an independent predictor of long-term survival. However, the shortage of organs makes it difficult to follow strict guidelines when placing hearts; therefore, decisions need to be made on a relative basis.

  4. Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma

    International Nuclear Information System (INIS)

    Farnebo, Jacob; Grybäck, Per; Harmenberg, Ulrika; Laurell, Anna; Wersäll, Peter; Blomqvist, Lennart K; Ullén, Anders; Sandström, Per

    2014-01-01

    To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression- free patient survival. Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression- free survival. Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression- free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression- free and overall survival in patients with mRCC

  5. Insurance and education predict long-term survival after orthotopic heart transplantation in the United States.

    Science.gov (United States)

    Allen, Jeremiah G; Weiss, Eric S; Arnaoutakis, George J; Russell, Stuart D; Baumgartner, William A; Shah, Ashish S; Conte, John V

    2012-01-01

    Insurance status and education are known to affect health outcomes. However, their importance in orthotopic heart transplantation (OHT) is unknown. The United Network for Organ Sharing (UNOS) database provides a large cohort of OHT recipients in which to evaluate the effect of insurance and education on survival. UNOS data were retrospectively reviewed to identify adult primary OHT recipients (1997 to 2008). Patients were stratified by insurance at the time of transplantation (private/self-pay, Medicare, Medicaid, and other) and college education. All-cause mortality was examined using multivariable Cox proportional hazard regression incorporating 15 variables. Survival was modeled using the Kaplan-Meier method. Insurance for 20,676 patients was distributed as follows: private insurance/self-pay, 12,298 (59.5%); Medicare, 5,227 (25.3%); Medicaid, 2,320 (11.2%); and "other" insurance, 831 (4.0%). Educational levels were recorded for 15,735 patients (76.1% of cohort): 7,738 (49.2%) had a college degree. During 53 ± 41 months of follow-up, 6,125 patients (29.6%) died (6.7 deaths/100 patient-years). Survival differed by insurance and education. Medicare and Medicaid patients had 8.6% and 10.0% lower 10-year survival, respectively, than private/self-pay patients. College-educated patients had 7.0% higher 10-year survival. On multivariable analysis, college education decreased mortality risk by 11%. Medicare and Medicaid increased mortality risk by 18% and 33%, respectively (p ≤ 0.001). Our study examining insurance and education in a large cohort of OHT patients found that long-term mortality after OHT is higher in Medicare/Medicaid patients and in those without a college education. This study points to potential differences in the care of OHT patients based on education and insurance status. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Being treated in higher volume hospitals leads to longer progression-free survival for epithelial ovarian carcinoma patients in the Rhone-Alpes region of France

    OpenAIRE

    Huguet, Marius; Perrier, Lionel; Bally, Olivia; Benayoun, David; De Saint Hilaire, Pierre; Beal Ardisson, Dominique; Morelle, Magali; Havet, Nathalie; Joutard, Xavier; Meeus, Pierre; Gabelle, Philippe; Provençal, Jocelyne; Chauleur, Céline; Glehen, Olivier; Charreton, Amandine

    2018-01-01

    Background To investigate the relationship between hospital volume activities and the survival for Epithelial Ovarian Carcinoma (EOC) patients in France. Methods This retrospective study using prospectively implemented databases was conducted on an exhaustive cohort of 267 patients undergoing first-line therapy during 2012 in the Rhone-Alpes Region of France. We compared Progression-Free Survival for Epithelial Ovarian Carcinoma patients receiving first-line therapy in high- (i.e. ≥ 12 cases/...

  7. Does hospital readmission following colorectal cancer resection and enhanced recovery after surgery affect long term survival?

    Science.gov (United States)

    Curtis, N J; Noble, E; Salib, E; Hipkiss, R; Meachim, E; Dalton, R; Allison, A; Ockrim, J; Francis, N K

    2017-08-01

    Hospital readmission is undesirable for patients and care providers as this can affect short-term recovery and carries financial consequences. It is unknown if readmission has long-term implications. We aimed to investigate the impact of 30-day readmission on long-term overall survival (OS) following colorectal cancer resection within enhanced recovery after surgery (ERAS) care and explore the reasons for and the severity and details of readmission episodes. A dedicated, prospectively populated database was reviewed. All patients were managed within an established ERAS programme. Five-year OS was calculated using the Kaplan-Meier method. The number, reason for and severity of 30-day readmissions were classified according to the Clavien-Dindo (CD) system, along with total (initial and readmission) length of stay (LoS). Multivariate analysis was used to identify factors predicting readmission. A total of 1023 consecutive patients underwent colorectal cancer resection between 2002 and 2015. Of these, 166 (16%) were readmitted. Readmission alone did not have a significant impact on 5-year OS (59% vs 70%, P = 0.092), but OS was worse in patients with longer total LoS (20 vs 14 days, P = 0.04). Of the readmissions, 121 (73%) were minor (CD I-II) and 27 (16%) required an intervention of which 16 (10%) were returned to theatre. Gut dysfunction 32 (19%) and wound complications 23 (14%) were the most frequent reasons for readmission. Prolonged initial LoS, rectal cancer and younger age predicted for hospital readmission. Readmission does not have a significant impact on 5-year OS. A broad range of conditions led to readmission, with the majority representing minor complications. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  8. Permanent vascular access survival in children on long-term chronic hemodialysis.

    Science.gov (United States)

    Briones, Liliana; Diaz Moreno, Alexia; Sierre, Sergio; Lopez, Laura; Lipsich, José; Adragna, Marta

    2010-09-01

    The aim of this study is to report a single-center experience regarding the management and outcome of permanent vascular accesses (VA) in children on chronic hemodialysis (HD). We analyzed the survival of permanent VA in 79 pediatric patients with end-stage renal disease patients on chronic HD between January 2000 and December 2008. One hundred and thirty-seven VA [89 native fistulas (AVFs) and 48 grafts (AVGs)] were created in 79 children. The creation of AVFs was significantly more frequent in children weighing >25 kg and AVGs in children weighing <25 kg (p = 0.003). The 1-year primary patency rate was 50% for AVF and 30% for AVG. The secondary patency rates at 1, 2, and 3 years for AVFs were 73, 50, and 20% and for AVGs were 64, 36, and 20%, respectively. The total number of surgical and endovascular interventions was significantly higher in AVGs (p long-term HD access in pediatrics. Surveillance and radiologic procedures are necessary for early detection and treatment of access complications in order to extend access survival.

  9. Preoperative atrial fibrillation and long-term survival after open heart surgery in a rural tertiary heart institute.

    Science.gov (United States)

    O'Neal, Wesley T; Efird, Jimmy T; Davies, Stephen W; Choi, Yuk Ming; Anderson, Curtis A; Kindell, Linda C; O'Neal, Jason B; Ferguson, T Bruce; Chitwood, W Randolph; Kypson, Alan P

    2013-01-01

    Preoperative atrial fibrillation (AF) is associated with increased morbidity and mortality after open heart surgery. However, the impact of preoperative AF on long-term survival after open heart surgery has not been widely examined in rural populations. Patients from rural regions are less likely to receive treatment for cardiac conditions and to have adequate medical insurance coverage. To examine the influence of preoperative AF on long-term survival following open heart surgery in rural eastern North Carolina. Long-term survival was compared in patients with and without preoperative AF after coronary artery bypass grafting (CABG) and CABG plus valve (CABG + V) surgery between 2002 and 2011. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. The study population consisted of 5438 patients. A total of 263 (5%) patients had preoperative AF. Preoperative AF was an independent predictor of long-term survival (open heart surgery: adjusted HR = 1.6, 95% CI = 1.3-2.0; CABG: adjusted HR = 1.6, 95% CI = 1.3-2.1; CABG + V: adjusted HR = 1.6, 95% CI = 1.1-2.3). Preoperative AF is an important predictor of long-term survival after open heart surgery in this rural population. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors.

    Science.gov (United States)

    Brabander, Tessa; van der Zwan, Wouter A; Teunissen, Jaap J M; Kam, Boen L R; Feelders, Richard A; de Herder, Wouter W; van Eijck, Casper H J; Franssen, Gaston J H; Krenning, Eric P; Kwekkeboom, Dik J

    2017-08-15

    Purpose: Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy. Experimental Design: For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq) 177 Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq) 177 Lu-DOTATATE before 2013 was further analyzed for efficacy and survival. Results: The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred. Conclusions: PRRT with 177 Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT with 177 Lu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months. Clin Cancer Res; 23(16); 4617-24. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Long-Term Survival of Individuals Born Small and Large for Gestational Age.

    Directory of Open Access Journals (Sweden)

    E Christina M Wennerström

    Full Text Available Little is known on long-term survival and causes of death among individuals born small or large for gestational age. This study investigates birth weight in relation to survival and causes of death over time.A national cohort of 1.7 million live-born singletons in Denmark was followed during 1979-2011, using the Danish Civil Registration System, the Medical Birth Registry and the Cause of Death Registry. Cox proportional hazards were estimated for the impact of small (SGA and large (LGA gestation weight and mortality overall, by age group and birth cohort.Compared to normal weight children, SGA children were associated with increased risk of dying over time. Though most of the deaths occurred during the first year of life, the cumulative mortality risk was increased until 30 years of age. The hazard ratios [HR] for dying among SGA children ages <2 years were: 3.47 (95% CI, 3.30-3.64 and 1.06 (95% CI, 0.60-1.87 in 30 years and older. HR for dying among SGA adults (20-29 years were: 1.20 (95% CI, 0.99-1.46 in years 1979-1982 and 1.61 (95% CI, 1.04-2.51 in years 1989-1994. The SGA born had increased risk of dying from infection, heart disease, respiratory disease, digestive disease, congenital malformation, perinatal conditions, and accidents, suicide, and homicide. Individuals born LGA were associated with decreased mortality risk, but with increased risk of dying from malignant neoplasm.Survival has improved independently of birth weight the past 30 years. However, children born SGA remain at significantly increased risk of dying up till they turn 30 years of age. Individuals born LGA have lower mortality risk but only in the first two years of life.

  12. Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients.

    Science.gov (United States)

    Liao, Yueh-Hsiang; Li, Chia-Ing; Lin, Cheng-Chieh; Lin, Jaung-Geng; Chiang, Jen-Huai; Li, Tsai-Chung

    2017-12-01

    Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database. A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61-0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72-0.91) and matched populations (0.86; 0.78-0.95). This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

  13. Long-term survival of hydrated resting eggs from Brachionus plicatilis.

    Science.gov (United States)

    Clark, Melody S; Denekamp, Nadav Y; Thorne, Michael A S; Reinhardt, Richard; Drungowski, Mario; Albrecht, Marcus W; Klages, Sven; Beck, Alfred; Kube, Michael; Lubzens, Esther

    2012-01-01

    Several organisms display dormancy and developmental arrest at embryonic stages. Long-term survival in the dormant form is usually associated with desiccation, orthodox plant seeds and Artemia cysts being well documented examples. Several aquatic invertebrates display dormancy during embryonic development and survive for tens or even hundreds of years in a hydrated form, raising the question of whether survival in the non-desiccated form of embryonic development depends on pathways similar to those occurring in desiccation tolerant forms. To address this question, Illumina short read sequencing was used to generate transcription profiles from the resting and amictic eggs of an aquatic invertebrate, the rotifer, Brachionus plicatilis. These two types of egg have very different life histories, with the dormant or diapausing resting eggs, the result of the sexual cycle and amictic eggs, the non-dormant products of the asexual cycle. Significant transcriptional differences were found between the two types of egg, with amictic eggs rich in genes involved in the morphological development into a juvenile rotifer. In contrast, representatives of classical "stress" proteins: a small heat shock protein, ferritin and Late Embryogenesis Abundant (LEA) proteins were identified in resting eggs. More importantly however, was the identification of transcripts for messenger ribonucleoprotein particles which stabilise RNA. These inhibit translation and provide a valuable source of useful RNAs which can be rapidly activated on the exit from dormancy. Apoptotic genes were also present. Although apoptosis is inconsistent with maintenance of prolonged dormancy, an altered apoptotic pathway has been proposed for Artemia, and this may be the case with the rotifer. These data represent the first transcriptional profiling of molecular processes associated with dormancy in a non-desiccated form and indicate important similarities in the molecular pathways activated in resting eggs compared

  14. Long-term survival of hydrated resting eggs from Brachionus plicatilis.

    Directory of Open Access Journals (Sweden)

    Melody S Clark

    Full Text Available Several organisms display dormancy and developmental arrest at embryonic stages. Long-term survival in the dormant form is usually associated with desiccation, orthodox plant seeds and Artemia cysts being well documented examples. Several aquatic invertebrates display dormancy during embryonic development and survive for tens or even hundreds of years in a hydrated form, raising the question of whether survival in the non-desiccated form of embryonic development depends on pathways similar to those occurring in desiccation tolerant forms.To address this question, Illumina short read sequencing was used to generate transcription profiles from the resting and amictic eggs of an aquatic invertebrate, the rotifer, Brachionus plicatilis. These two types of egg have very different life histories, with the dormant or diapausing resting eggs, the result of the sexual cycle and amictic eggs, the non-dormant products of the asexual cycle. Significant transcriptional differences were found between the two types of egg, with amictic eggs rich in genes involved in the morphological development into a juvenile rotifer. In contrast, representatives of classical "stress" proteins: a small heat shock protein, ferritin and Late Embryogenesis Abundant (LEA proteins were identified in resting eggs. More importantly however, was the identification of transcripts for messenger ribonucleoprotein particles which stabilise RNA. These inhibit translation and provide a valuable source of useful RNAs which can be rapidly activated on the exit from dormancy. Apoptotic genes were also present. Although apoptosis is inconsistent with maintenance of prolonged dormancy, an altered apoptotic pathway has been proposed for Artemia, and this may be the case with the rotifer.These data represent the first transcriptional profiling of molecular processes associated with dormancy in a non-desiccated form and indicate important similarities in the molecular pathways activated in

  15. Association of perioperative blood pressure with long-term survival in rectal cancer patients.

    Science.gov (United States)

    Yu, Hui-Chuan; Luo, Yan-Xin; Peng, Hui; Wang, Xiao-Lin; Yang, Zi-Huan; Huang, Mei-Jin; Kang, Liang; Wang, Lei; Wang, Jian-Ping

    2016-04-11

    Several studies suggested that hypertension is positively related to cancer incidence and mortality. In this study, we investigated the association between perioperative blood pressure (BP) and long-term survival outcomes in patients with rectal cancer. This study included a cohort of 358 patients with stages I-III rectal cancer who underwent a curative resection between June 2007 and June 2011. Both pre- and postoperative BPs were measured, by which patients were grouped (low BP: cancer-specific survival (CSS). Univariate analysis showed that patients with high preoperative systolic BP had lower 3-year DFS (67.2% vs. 82.1%, P = 0.041) and CSS rates (81.9% vs. 94.8%, P = 0.003) than patients with low preoperative systolic BP, and the associations remained significant in the Cox multivariate analysis, with the adjusted hazard ratios equal to 1.97 [95% confidence interval (CI) = 1.08-3.60, P = 0.028] and 2.85 (95% CI = 1.00-8.25, P = 0.050), respectively. Similarly, in postoperative evaluation, patients with high systolic BP had significantly lower 3-year CSS rates than those with low systolic BP (78.3% vs. 88.9%, P = 0.032) in univariate analysis. Moreover, high pre- and/or postoperative systolic BP presented as risk factors for CSS in the subgroups of patients who did not have a history of hypertension, with and/or without perioperative administration of antihypertensive drugs. High preoperative systolic BP was an independent risk factor for both CSS and DFS rates, and high postoperative systolic BP was significantly associated with a low CSS rate in rectal cancer patients. Additionally, our results suggest that rectal cancer patients may get survival benefit from BP control in perioperative care. However, further studies should be conducted to determine the association between BP and CSS and targets of BP control.

  16. Timely disclosure of progress in long-term cancer survival: the boomerang method substantially improved estimates in a comparative study.

    Science.gov (United States)

    Brenner, Hermann; Jansen, Lina

    2016-02-01

    Monitoring cancer survival is a key task of cancer registries, but timely disclosure of progress in long-term survival remains a challenge. We introduce and evaluate a novel method, denoted "boomerang method," for deriving more up-to-date estimates of long-term survival. We applied three established methods (cohort, complete, and period analysis) and the boomerang method to derive up-to-date 10-year relative survival of patients diagnosed with common solid cancers and hematological malignancies in the United States. Using the Surveillance, Epidemiology and End Results 9 database, we compared the most up-to-date age-specific estimates that might have been obtained with the database including patients diagnosed up to 2001 with 10-year survival later observed for patients diagnosed in 1997-2001. For cancers with little or no increase in survival over time, the various estimates of 10-year relative survival potentially available by the end of 2001 were generally rather similar. For malignancies with strongly increasing survival over time, including breast and prostate cancer and all hematological malignancies, the boomerang method provided estimates that were closest to later observed 10-year relative survival in 23 of the 34 groups assessed. The boomerang method can substantially improve up-to-dateness of long-term cancer survival estimates in times of ongoing improvement in prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Practice patterns and long-term survival for early-stage rectal cancer.

    Science.gov (United States)

    Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

    2013-12-01

    Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

  18. Long-term survival with unfavourable outcome: a qualitative and ethical analysis.

    Science.gov (United States)

    Honeybul, Stephen; Gillett, Grant R; Ho, Kwok M; Janzen, Courtney; Kruger, Kate

    2015-12-01

    To assess the issue of 'retrospective consent' among a cohort of patients who had survived with unfavourable outcome and to assess attitudes among next of kin regarding their role as surrogate decision makers. Twenty patients who had survived for at least 3 years with an unfavourable outcome following a decompressive craniectomy for severe traumatic brain injury were assessed with their next of kin. During the course of a semistructured interview, participants were asked whether they would have provided consent if they had known their eventual outcome. They were also asked for general comments regarding all aspects of the clinical journey. Eighteen patients had next of kin who were available for interview. For two patients, there was no longer any family involvement. Of the 20 patients, 13 were able to provide a response and 11 felt that they would have provided consent even if they had known their eventual outcome. Of the 18 next of kin who were able to express an opinion, 10 felt that they would have provided retrospective consent. Many patients appeared to have adapted to a level of disability that competent individuals might deem unacceptable. This does not necessarily mean that such outcomes should be regarded as 'favourable', nor that decompressive craniectomy must be performed for patients with predicted poor outcome. Nevertheless, those burdened with the initial clinical decisions and thereafter the long-term care of these patients may draw some support from the knowledge that unfavourable may not necessarily be unacceptable. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. Long-term survival after acute myocardial infarction is lower in more deprived neighborhoods.

    Science.gov (United States)

    Tonne, Cathryn; Schwartz, Joel; Mittleman, Murray; Melly, Steve; Suh, Helen; Goldberg, Robert

    2005-06-14

    As part of the Worcester Heart Attack Study, a community-wide study examining changes over time in the incidence and long-term case-fatality rates of greater Worcester, Mass, residents hospitalized with confirmed acute myocardial infarction (AMI), we investigated the hypothesis that census tract-level socioeconomic position is an important predictor of survival after hospital discharge for AMI, after adjusting for demographic and clinical characteristics. Data were available for 3423 confirmed cases of AMI among metropolitan Worcester residents during the 4 study years of 1995, 1997, 1999, and 2001 who were followed up through the end of 2002. The mean age among patients was 69 years, and 58% were men. Using a multilevel Cox proportional hazards regression model, we estimated a 30% higher death rate after AMI for patients living in census tracts with the most residents living below the poverty line compared with patients living in the wealthiest census tracts (relative risk=1.30; 95% CI, 1.08 to 1.56). Similarly, patients living in census tracts with the highest proportion of residents with less than a high school education experienced a 47% higher death rate than patients living in census tracts with the lowest proportion of residents with less than a high school education (relative risk=1.47; 95% CI, 1.15 to 1.88). Within a medium-sized urban area, there are important variations in survival after hospital discharge for AMI that are associated with socioeconomic position. These associations persist after adjustment for demographic and clinical characteristics. Reasons for these differences warrant further investigation.

  20. Pretreatment F-18 FDG PET/CT Parameters to Evaluate Progression-Free Survival in Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeonghun; Lim, Seok Tae; Na, Chang Ju; Han, Yeonhee; Kim, Chanyoung; Jeong, Hwanjeong; Sohn, Myunghee [Chonbuk National Univ., Jeonju (Korea, Republic of)

    2014-03-15

    We performed this study to evaluate the predictive value of pretreatment F-18 FDG PET/CT for progression-free survival (PFS) in patients with gastric cancer. Of 321 patients with a diagnosis of gastric cancer, we retrospectively enrolled 97 patients (men:women = 61:36, age 59.8±13.2 years), who underwent pretreatment F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) from January 2009 to December 2009. Maximum standardized uptake value (SUVmax) was measured for each case with detectable primary lesions. In the remaining non-detectable cases, SUVmax was measured from the corresponding site seen on gastroduodenoscopy for analysis. In subgroup analysis, metabolic tumor volume (MTV) was measured in 50 patients with clearly distinguishable primary lesions. SUVmax, stage, depth of tumor invasion and presence of lymph node metastasis were analyzed in terms of PFS. Receiver operating characteristic (ROC) curves were used to find optimal cutoff values of SUVmax and MTV for disease progression. The relationship between SUVmax, MTV and PFS was analyzed using the Kaplan-Meier with log-rank test and Cox's proportional hazard regression methods. Of 97 patients, 15 (15.5 %) had disease progression. The mean follow-up duration was 29.6±10.2 months. The mean PFS of low SUVmax group (≤5.74) was significantly longer than that of the high SUVmax group (>5.74) (30.9±8.0 vs 24.3±13.6 months, p =0.008). In univariate analysis, stage (I vs II, III, IV), depth of tumor invasion (T1 vs T2, T3, T4), presence of lymph node metastasis and SUVmax (>5.74 vs ≤5.74) were significantly associated with recurrence. In multivariate analysis, high SUVmax (>5.74) was the only poor prognostic factor for PFS (p =0.002, HR 11.03, 95% CI 2.48.49.05). Subgroup multivariate analysis revealed that high MTV (>16.42) was the only poor prognostic factor for PFS (p =0.034, HR 3.59, 95 % CI 1.10.11.71). In gastric cancer, SUVmax measured by pretreatment F-18

  1. Decayed, missing and filled teeth and dental anomalies in long term survived leukemic children: a prospective controlled study

    OpenAIRE

    Lauritano, D; Petruzzi, M; Baldoni, M

    2012-01-01

    Objective: The aim of this prospective controlled study is the comparison between long-term children survived leukaemia and a control group in terms of the decayed, missing or filled permanent teeth (DMFT) and dental anomalies. Study design: Fifty-two long term children survived leukaemia, aged from 8 to 15 years (27 females, 25 males; mean age 11.5 years) were evaluated for the possible effects of the anti-leukaemic therapy on dental development and compared to a control group of 52 healthy ...

  2. Long-Term Survival, Quality of Life, and Quality-Adjusted Survival in Critically Ill Patients With Cancer.

    Science.gov (United States)

    Normilio-Silva, Karina; de Figueiredo, Adelaide Cristina; Pedroso-de-Lima, Antonio Carlos; Tunes-da-Silva, Gisela; Nunes da Silva, Adriana; Delgado Dias Levites, Andresa; de-Simone, Ana Tereza; Lopes Safra, Patrícia; Zancani, Roberta; Tonini, Paula Camilla; Vasconcelos de Andrade E Silva, Ulysses; Buosi Silva, Thiago; Martins Giorgi, Juliana; Eluf-Neto, José; Costa, Anderson; Abrahão Hajjar, Ludhmila; Biasi Cavalcanti, Alexandre

    2016-07-01

    To assess the long-term survival, health-related quality of life, and quality-adjusted life years of cancer patients admitted to ICUs. Prospective cohort. Two cancer specialized ICUs in Brazil. A total of 792 participants. None. The health-related quality of life before ICU admission; at 15 days; and at 3, 6, 12, and 18 months was assessed with the EQ-5D-3L. In addition, the vital status was assessed at 24 months. The mean age of the subjects was 61.6 ± 14.3 years, 42.5% were female subjects and half were admitted after elective surgery. The mean Simplified Acute Physiology Score 3 was 47.4 ± 15.6. Survival at 12 and 18 months was 42.4% and 38.1%, respectively. The mean EQ-5D-3L utility measure before admission to the ICU was 0.47 ± 0.43, at 15 days it was 0.41 ± 0.44, at 90 days 0.56 ± 0.42, at 6 months 0.60 ± 0.41, at 12 months 0.67 ± 0.35, and at 18 months 0.67 ± 0.35. The probabilities for attaining 12 and 18 months of quality-adjusted survival were 30.1% and 19.1%, respectively. There were statistically significant differences in survival time and quality-adjusted life years according to all assessed baseline characteristics (ICU admission after elective surgery, emergency surgery, or medical admission; Simplified Acute Physiology Score 3; cancer extension; cancer status; previous surgery; previous chemotherapy; previous radiotherapy; performance status; and previous health-related quality of life). Only the previous health-related quality of life and performance status were associated with the health-related quality of life during the 18-month follow-up. Long-term survival, health-related quality of life, and quality-adjusted life year expectancy of cancer patients admitted to the ICU are limited. Nevertheless, these clinical outcomes exhibit wide variability among patients and are associated with simple characteristics present at the time of ICU admission, which may help healthcare professionals estimate patients

  3. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

    Science.gov (United States)

    Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

    2014-01-01

    Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

  4. Progression-free survival/time to progression as a potential surrogate for overall survival in HR+, HER2– metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Forsythe A

    2018-05-01

    Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,2 Gabriel Tremblay1 1Purple Squirrel Economics, New York, NY, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Novartis Pharma GmbH, Nuremberg, Germany; 4Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada Background: Several recent randomized controlled trials (RCTs in hormone receptor-positive (HR+, human epidermal growth factor receptor 2-negative (HER2– metastatic breast cancer (MBC have demonstrated significant improvements in progression-free survival (PFS; however, few have reported improvement in overall survival (OS. The surrogacy of PFS or time to progression (TTP for OS has not been formally investigated in HR+, HER2– MBC.Methods: A systematic literature review of RCTs in HR+, HER2– MBC was conducted to identify studies that reported both median PFS/TTP and OS. The correlation between PFS/TTP and OS was evaluated using Pearson’s product–moment correlation and Spearman’s rank correlation. Subgroup analyses were performed to explore possible reasons for heterogeneity. Errors-in-variables weighted least squares regression (LSR was used to model incremental OS months as a function of incremental PFS/TTP months. An exploratory analysis investigated the impact of three covariates (chemotherapy vs hormonal/targeted therapy, PFS vs TTP, and first-line therapy vs second-line therapy or greater on OS prediction. The lower 95% prediction band was used to determine the minimum incremental PFS/TTP months required to predict OS benefit (surrogate threshold effect [STE].Results: Forty studies were identified. There was a statistically significant correlation between median PFS/TTP and OS (Pearson =0.741, P=0.000; Spearman =0.650, P=0.000. These results proved consistent for chemotherapy and hormonal/targeted therapy. Univariate LSR analysis yielded an R2 of 0.354 with 1 incremental PFS/TTP month corresponding to 1.13 incremental OS months

  5. Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis.

    Science.gov (United States)

    Ost, Piet; Jereczek-Fossa, Barbara Alicja; As, Nicholas Van; Zilli, Thomas; Muacevic, Alexander; Olivier, Kenneth; Henderson, Daniel; Casamassima, Franco; Orecchia, Roberto; Surgo, Alessia; Brown, Lindsay; Tree, Alison; Miralbell, Raymond; De Meerleer, Gert

    2016-01-01

    The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15-26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. This multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival. Copyright © 2015. Published by Elsevier B.V.

  6. Long-term survival in patients hospitalized for chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Gudmundsson, Gunnar; Ulrik, Charlotte Suppli; Gislason, Thorarinn

    2012-01-01

    Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD). Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.......Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD). Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation....

  7. In vivo studies of the long-term 51Cr red cell survival of serologically incompatible red cell units

    International Nuclear Information System (INIS)

    Baldwin, M.L.; Ness, P.M.; Barrasso, C.; Kickler, T.S.; Drew, H.; Tsan, M.F.; Shirey, R.S.

    1985-01-01

    The long-term survival of serologically incompatible red cell units was measured in five patients with antibodies to high-frequency antigens. Initially, the survival of 1 ml of 51 Cr-labeled incompatible red cells was measured over 1 hour. After demonstrating that the 1-hour survival times were successful (greater than 70%), each patient then received 5 ml of the same 51 Cr-labeled red cells followed by the transfusion of the remainder of the red cell unit. The long-term T 1/2Cr survival for each case was patient 1 (anti-McCa), 15 days; patient 2 (anti-JMH), 12 days; patient 3 (anti-Kna), 31 days; patient 4 (anti-McCa), 12 days; and patient 5 (anti-Hya), 14 days. Each antibody tested in an in vitro homologous macrophage assay showed less than 5 percent phagocytosis. Anti-JMH was the only antibody to react with IgG subclass antisera and was determined to be IgG4. The macrophage assay, IgG subclass testing, and short-term (1 hour, 1 ml) 51 Cr survival studies all indicated that the short-term survival was good. However, only the measurement of long-term survival with transfused units of serologically incompatible red cells was able to determine the actual survival, and clinical significance of the alloantibodies. Determining the actual long-term survival by the method described here can be of importance for patients requiring chronic red cell transfusion

  8. Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

    Science.gov (United States)

    Zanin, M P; Hellström, M; Shepherd, R K; Harvey, A R; Gillespie, L N

    2014-09-26

    Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Active smoking may negatively affect response rate, progression-free survival, and overall survival of patients with metastatic renal cell carcinoma treated with sunitinib.

    Science.gov (United States)

    Keizman, Daniel; Gottfried, Maya; Ish-Shalom, Maya; Maimon, Natalie; Peer, Avivit; Neumann, Avivit; Hammers, Hans; Eisenberger, Mario A; Sinibaldi, Victoria; Pili, Roberto; Hayat, Henry; Kovel, Svetlana; Sella, Avishay; Boursi, Ben; Weitzen, Rony; Mermershtain, Wilmosh; Rouvinov, Keren; Berger, Raanan; Carducci, Michael A

    2014-01-01

    Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC). An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors. Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p 3 (HR: 2.95, p smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC.

  10. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

    NARCIS (Netherlands)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2016-01-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low

  11. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

    NARCIS (Netherlands)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2016-01-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose

  12. Predictive value of the Status Epilepticus Severity Score (STESS) and its components for long-term survival

    DEFF Research Database (Denmark)

    Aukland, Preben; Lando, Martin; Vilholm, Ole

    2016-01-01

    BACKGROUND: The "Status Epilepticus Severity Score" (STESS) is the most important clinical score to predict in-hospital mortality of patients with status epilepticus (SE), but its prognostic relevance for long-term survival is unknown. This study therefore examined if STESS and its components...

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

    Science.gov (United States)

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

    2017-10-01

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

  14. Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

    NARCIS (Netherlands)

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J. A.; Douillard, Jean-Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

    2015-01-01

    Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual

  15. Long-term Survival of Six Patients with Glioblastoma Multiforme: Case Series and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Shapour Omidvari

    2012-04-01

    Full Text Available The median overall survival in glioblastoma multiforme is usually less than one year. Long-term survival is rare and is seen in only 3%-6% of GBM patients. The present study reports the characteristics and treatment outcomes of six cases of glioblastoma multiforme with long-term survival. A literature review is also presented.Between 1990 and 2008, 217 glioblastoma multiforme patients have been treated at our center of which six cases (four males survived for three years or longer. The mean age of the six cases was 25.7 years. All patients received postoperative radiotherapy with a mean dose of 55 gray and four patients received nitrosourea-based chemotherapy.Patients' mean survival was 5.2 years. The results of this study and review of the literature have indicated that long-term (more than three years survival is exceptional and mainly observed in younger patients with good performance status and following complete surgical tumor resection.

  16. Effect of PS-K on long-term survival of primary lung cancer patients treated with radiation

    International Nuclear Information System (INIS)

    Okazaki, Atsushi; Nakajima, Nobuaki; Hayakawa, Kazushige; Saito, Yoshihiro; Mitomo, Osamu; Niibe, Hideo

    1984-01-01

    The effect of PS-K on long-term survival of primary lung cancer patients irradiated over 60 Gy through 1977 to 1982 was studied. PS-K was administrated orally 3.0 g, daily or intermittently in the pattern of 2 weeks per a month on patients of positive PPD skin test. All cases irradiated over 60 Gy were 174 (Group A) containing 62 cases with PS-K (Group B) and 112 cases without PS-K (Group C). Of group B, 44 cases were administrated within a month after curative irradiation (Group B1), 7 cases were administrated on time maintaining long-term good condition after irradiation (Group B2) and 11 cases were administrated after recognition of recurrence or metastasis (Group B3). Following results were obtained. 1. Obvious prolongation of survivals was recognized in the patients with PS-K after irradiation. (1) The cumulative 5 years survival rates of Group A, B 1 and C were 11.0%, 28.8% and 4.8%, respectively. (2) The cumulative 5 years survival rates of stage I,11 were 45.7% with PS-K and 10.7% without PS-K. (3) The cumulative 5 years survival rates of 21 cases matched age, sex, stage, histological type and tumor dose with and without PS-K were 37.8% and 7.2%. (4) In Group B 2, 5 cases out of 7 cases have been alived, but in Group B 3, satisfactory long-term survivals ware not obtained. 2. The necessary conditions which obtain long-term survival with PS-K were thought to be follows. One is that the tumor is brought almost to vanish by irradiation. Another is that the condition of host is superior to that of tumor in host-tumor relationship. 3. The possibility of intermittent administration of PS-K was suggested. (author)

  17. Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Rolf Warta

    Full Text Available Drug transporters such as P-glycoprotein (ABCB1 have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels of a subset of drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR or protein expression by tissue microarray (TMA in tumor samples of therapy naïve stage IV head and neck squamous cell carcinoma (HNSCC (qRT-PCR, n = 40; TMA, n = 61, this in situ study re-examined the significance of transporter expression for progression-free survival (PFS and overall survival (OS. Data from The Cancer Genome Atlas database was used to externally validate the respective findings (n = 317. In general, HNSCC tended to lower expression of drug transporters compared to normal epithelium. High ABCB1 mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357 and overall survival (OS, p = 0.0535. Similar results were obtained for the mRNA of ABCC1 (MRP1, multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038. In contrast, protein expression of ATP7b (copper transporter ATP7b, mRNA expression of ABCG2 (BCRP, breast cancer resistance protein, ABCC2 (MRP2, and SLC31A1 (hCTR1, human copper transporter 1 did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of drug efflux transporters indicates poor survival, but demonstrates that expression of single drug transporters might indicate even improved survival. Prospectively, combined analysis of the 'transportome' should rather be performed as it likely unravels meaningful data on the impact of drug transporters on survival of patients with HNSCC.

  18. Predictors of long-term survival among first-ever ischemic and hemorrhagic stroke in a Brazilian stroke cohort.

    Science.gov (United States)

    Goulart, Alessandra C; Fernandes, Tiotrefis G; Santos, Itamar S; Alencar, Airlane P; Bensenor, Isabela M; Lotufo, Paulo A

    2013-05-24

    Few studies have examined both ischemic and hemorrhagic stroke to identify prognostic factors associated to long-term stroke survival. We investigated long-term survival and predictors that could adversely influence ischemic and hemorrhagic first-ever stroke prognosis. We prospectively ascertained 665 consecutive first-ever ischemic and hemorrhagic stroke cases from "The Study of Stroke Mortality and Morbidity" (The EMMA Study) in a community hospital in São Paulo, Brazil. We evaluated cardiovascular risk factors and sociodemographic characteristics (age, gender, race and educational level). We found a lower survival rate among hemorrhagic cases compared to ischemic stroke cases at the end of 4 years of follow-up (52% vs. 44%, p = 0.04). The risk of death was two times higher among people with ischemic stroke without formal education. Also, we found consistently higher risk of death for diabetics with ischemic stroke (HR = 1.45; 95% CI = 1.07-1.97) compared to no diabetics. As expected, age equally influenced on the high risk of poor survival, regardless of stroke subtype. For ischemic stroke, the lack of formal education and diabetes were significant independent predictors of poor long-term survival.

  19. Surviving in Changing Seascapes: Sediment Dynamics as Bottleneck for Long-Term Seagrass Presence

    NARCIS (Netherlands)

    Suykerbuyk, W.; Bouma, T.J.; Govers, L.L.; Giesen, K.; de Jong, D.J.; Herman, P.M.J.; Hendriks, J.; van Katwijk, M.M.

    2016-01-01

    Changes in the seascape often result in altered hydrodynamics that lead to coinciding changes in sediment dynamics. Little is known on how altered sediment dynamics affect long-term seagrass persistence. We studied the thresholds of sediment dynamics in relation to seagrass presence by comparing

  20. Surviving the Holocaust: A Meta-Analysis of the Long-Term Sequelae of a Genocide

    Science.gov (United States)

    Barel, Efrat; Van Ijzendoorn, Marinus H.; Sagi-Schwartz, Abraham; Bakermans-Kranenburg, Marian J.

    2010-01-01

    The current set of meta-analyses elucidates the long-term psychiatric, psychosocial, and physical consequences of the Holocaust for survivors. In 71 samples with 12,746 participants Holocaust survivors were compared with their counterparts (with no Holocaust background) on physical health, psychological well-being, posttraumatic stress symptoms,…

  1. Is progression-free survival a more relevant endpoint than overall survival in first-line HR+/HER2− metastatic breast cancer?

    Directory of Open Access Journals (Sweden)

    Forsythe A

    2018-05-01

    Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,5 Anastasiya Shor,1 Gabriel Tremblay6 1Health Technology Assessment Evidence, Purple Squirrel Economics, New York, NY, USA; 2Global Value and Access, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 3German Market Access, Novartis Pharma GmbH, Nuremberg, Germany; 4Health Policy and Patient Access, Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada; 5Global Medical Affairs (Oncology Business Unit, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 6Health Economics, Purple Squirrel Economics, New York, NY, USA Background: Hormone receptor-positive (HR+, human epidermal growth factor receptor 2- negative (HER2−, metastatic breast cancer (MBC accounts for 73% of all MBCs. Endocrine therapy (ET is the basis of first-line (1L therapy for patients with HR+/HER2− MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS benefit to date. We reviewed studies of HR+/HER2− MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL. Methods: The Embase®, Medline®, and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2− MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs, observational, and retrospective studies were included. Results: Seventy-nine RCTs were identified: 58 (73% in the 1L+ setting and 21 (27% in second-line or greater settings. PFS hazard ratios (HRs were reported in 61 (77% studies; 31 (39% reported significant PFS improvements. OS was reported in 44 (41% studies; 12 (15% reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8% studies

  2. Severity of acidosis affects long-term survival in COPD patients with hypoxemia after intensive care unit discharge.

    Science.gov (United States)

    Gungor, Sinem; Kargin, Feyza; Irmak, Ilim; Ciyiltepe, Fulya; Acartürk Tunçay, Eylem; Atagun Guney, Pinar; Aksoy, Emine; Ocakli, Birsen; Adiguzel, Nalan; Karakurt, Zuhal

    2018-01-01

    Patients admitted to the intensive care unit (ICU) with acute respiratory failure (ARF) due to COPD have high mortality and morbidity. Acidosis has several harmful effects on hemodynamics and metabolism, and the current knowledge regarding the relationship between respiratory acidosis severity on the short- and long-term survival of COPD patients is limited. We hypothesized that COPD patients with severe acidosis would have a poorer short- and long-term prognosis compared with COPD patients with mild-to-moderate acidosis. This retrospective observational cohort study was conducted in a level III respiratory ICU of a tertiary teaching hospital for chest diseases between December 1, 2013, and December 30, 2014. Subject characteristics, comorbidities, ICU parameters, duration of mechanical ventilation, length of ICU stay, ICU mortality, use of domiciliary noninvasive mechanical ventilation (NIMV) and long-term oxygen therapy (LTOT), and short- and long-term mortality were recorded. Patients were grouped according to their arterial blood gas (ABG) values during ICU admission: severe acidotic (pH≤7.20) and mild-to-moderate acidotic (pH 7.21-7.35). These groups were compared with the recorded data. The mortality predictors were analyzed by logistic regression test in the ICU and the Cox regression test for long-term mortality predictors. During the study period, a total of 312 COPD patients admitted to the ICU with ARF, 69 (72.5% male) in the severe acidosis group and 243 (79% male) in the mild-to-moderate acidosis group, were enrolled. Group demographics, comorbidities, duration of mechanical ventilation, and length of ICU stay were similar in the two groups. The severe acidosis group had a significantly higher rate of NIMV failure (60.7% vs 40%) in the ICU. Mild-to-moderate acidotic COPD patients using LTOT had longer survival after ICU discharge than those without LTOT. On the other hand, severely acidotic COPD patients without LTOT showed shorter survival than

  3. [Long term effect of hepatitis B and C virus infection on the survival of kidney transplant patients].

    Science.gov (United States)

    Corrêa, José Roberto Missel; Rocha, Fabrício Domingos; Peres, Alessandro Afonso; Gonçalves, Luiz Felipe; Manfro, Roberto Ceratti

    2003-01-01

    To evaluate the impact of HCV (hepatitis C virus) and HBV (hepatitis B virus) infection on long-term graft and patient survival in renal transplantation. One hundred and nine kidney allograft recipients were evaluated regarding the presence of antibodies against HCV and hepatitis B surface antigen. Patients were divided into four groups according to their serologic status and followed for ten years for survival analysis. Age, gender, renal failure etiology, length of previous dialysis and post transplantation periods were evaluated. Length on dialysis time was significantly longer in the anti-HCV positive group. There was also a higher number of patients with re-transplants in the HBV and HCV groups. There were no significant differences in 10-year patient survival in the anti-HCV positive group (71.0%; relative risk: 1.13; CI: 0.86-1.47) and in the HBV infected group (77.8%; relative risk: 1.03; CI: 0.7-1.5) compared to the not infected group (80%). However, the group of patients infected with both viruses presented a significantly lower 10-year patient survival (37.5%; relative risk: 2.13; CI: 0.86-5.28) compared to the index group. There were no significant differences on graft survival among the groups. In the present study renal transplant patients infected concomitantly with HBV and HCV present a significantly lower long-term patient survival.

  4. Long-Term Survival after Stroke: 30 Years of Follow-Up in a Cohort, the Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Boysen, G.; Marott, J.L.; Gronbaek, M.

    2009-01-01

    in the Copenhagen City Heart Study who experienced a first-ever stroke from 1978 to the end of 2001 were followed to the end of 2007. Stroke events were validated using the World Health Organization's definition of stroke. Linkage to the Danish Civil Registration System enabled identification of participants who...... died before the end of 2007. The National Register of Causes of Death provided cause of death. Survival in stroke patients was compared with survival in participants in the Copenhagen City Heart Study who did not suffer a stroke, and with survival in the general Danish population. Cox regression......-stroke controls. Long-term survival improved steadily over time. Life expectancy after stroke increased up to 4 years from 1978 to the end of 2001, exceeding the increase of life expectancy in the general population. Slightly longer survival was found in women than in men when adjusted for age at stroke onset...

  5. Repair or Replacement for Isolated Tricuspid Valve Pathology? Insights from a Surgical Analysis on Long-Term Survival

    Science.gov (United States)

    Farag, Mina; Arif, Rawa; Sabashnikov, Anton; Zeriouh, Mohamed; Popov, Aron-Frederik; Ruhparwar, Arjang; Schmack, Bastian; Dohmen, Pascal M.; Szabó, Gábor; Karck, Matthias; Weymann, Alexander

    2017-01-01

    Background Long-term follow-up data concerning isolated tricuspid valve pathology after replacement or reconstruction is limited. Current American Heart Association guidelines equally recommend repair and replacement when surgical intervention is indicated. Our aim was to investigate and compare operative mortality and long-term survival in patients undergoing isolated tricuspid valve repair surgery versus replacement. Material/Methods Between 1995 and 2011, 109 consecutive patients underwent surgical correction of tricuspid valve pathology at our institution for varying structural pathologies. A total of 41 (37.6%) patients underwent tricuspid annuloplasty/repair (TAP) with or without ring implantation, while 68 (62.3%) patients received tricuspid valve replacement (TVR) of whom 36 (53%) were mechanical and 32 (47%) were biological prostheses. Results Early survival at 30 days after surgery was 97.6% in the TAP group and 91.1% in the TVR group. After 6 months, 89.1% in the TAP group and 87.8% in the TVR group were alive. In terms of long-term survival, there was no further mortality observed after one year post surgery in both groups (Log Rank p=0.919, Breslow p=0.834, Tarone-Ware p=0.880) in the Kaplan-Meier Survival analysis. The 1-, 5-, and 8-year survival rates were 85.8% for TAP and 87.8% for TVR group. Conclusions Surgical repair of the tricuspid valve does not show survival benefit when compared to replacement. Hence valve replacement should be considered generously in patients with reasonable suspicion that regurgitation after repair will reoccur. PMID:28236633

  6. Effects of bystander CPR following out-of-hospital cardiac arrest on hospital costs and long-term survival.

    Science.gov (United States)

    Geri, Guillaume; Fahrenbruch, Carol; Meischke, Hendrika; Painter, Ian; White, Lindsay; Rea, Thomas D; Weaver, Marcia R

    2017-06-01

    Bystander cardiopulmonary resuscitation (CPR) is associated with a greater likelihood of survival to hospital discharge after out-of-hospital cardiac arrest (OHCA). However the long-term survival benefits in relationship to cost have not been well-studied. We evaluated bystander CPR, hospital-based costs, and long-term survival following OHCA in order to assess the potential cost-effectiveness of bystander CPR. We conducted a retrospective cohort study of consecutive EMS-treated OHCA patients >=12years who arrested prior to EMS arrival and outside a nursing facility between 2001 and 2010 in greater King County, WA. Utstein-style information was obtained from the EMS registry, including 5-year survival. Costs from the OHCA hospitalization were obtained from the Washington State Comprehensive Hospital Abstract Reporting System. Cost effectiveness was based on hospital costs divided by quality-adjusted life years (QALYs) for a 5-year follow-up window. Of the 4448 eligible patients, 18.5% (n=824) were discharged alive from hospital and 12.1% (n=539) were alive at 5 years. Five-year survival was higher in patients who received bystander CPR (14.3% vs. 8.7%, pbystander CPR. The average (SD) total cost of the initial acute care hospitalization was USD 19,961 (40,498) for all admitted patients and USD 75,175 (52,276) for patients alive at year 5. The incremental cost-effectiveness ratio associated with bystander CPR was USD 48,044 per QALY. Based on this population-based investigation, bystander CPR was positively associated with long-term survival and appears cost-effective. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer

    Science.gov (United States)

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-01-01

    Abstract Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm2/m2 for women and 40.8 cm2/m2 for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia is independently associated with overall and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. PMID:27043677

  8. Outcomes and long-term survival of coronary artery surgery: The controversial role of opium as risk marker

    Science.gov (United States)

    Najafi, Mahdi; Jahangiry, Leila; Mortazavi, Seyedeh Hamideh; Jalali, Arash; Karimi, Abbasali; Bozorgi, Ali

    2016-01-01

    AIM To study survival in isolated coronary artery bypass graft (CABG) patients and to evaluate the impact of preoperative chronic opium consumption on long-term outcome. METHODS Cohort of 566 isolated CABG patients as Tehran Heart Center cardiac output measurement was conducted. Daily evaluation until discharge as well as 4- and 12-mo and 6.5-year follow-up information for survival status were fulfilled for all patients. Long-term 6.5-year overall and opium-stratified survival, adjusted survival curves based on opium consumption as well as possible predictors of all-cause mortality using multiple cox regression were determined by statistical analysis. RESULTS Six point five-year overall survival was 91.8%; 86.6% in opium consumers and 92.7% in non-opium consumers (P = 0.035). Patients with positive history of opium consumption significantly tended to have lower ejection fraction (EF), higher creatinine level and higher prevalence of myocardial infarction. Multiple predictors of all-cause mortality included age, body mass index, EF, diabetes mellitus and cerebrovascular accident. The hazard ratio (HR) of 2.09 for the risk of mortality in opium addicted patients with a borderline P value (P = 0.052) was calculated in this model. Further adjustment with stratification based on smoking and opium addiction reduced the HR to 1.20 (P = 0.355). CONCLUSION Simultaneous impact of smoking as a confounding variable in most of the patients prevents from definitive judgment on the role of opium as an independent contributing factor in worse long-term survival of CABG patients in addition to advanced age, low EF, diabetes mellitus and cerebrovascular accident. Meanwhile, our findings do not confirm any cardio protective role for opium to improve outcome in coronary patients with the history of smoking. Further studies are needed to clarify pure effect of opium and warrant the aforementioned findings. PMID:27957254

  9. Surviving colorectal cancer: long-term, persistent ostomy-specific concerns and adaptations.

    Science.gov (United States)

    Sun, Virginia; Grant, Marcia; McMullen, Carmit K; Altschuler, Andrea; Mohler, M Jane; Hornbrook, Mark C; Herrinton, Lisa J; Baldwin, Carol M; Krouse, Robert S

    2013-01-01

    The purpose of this article was to describe persistent ostomy-specific concerns and adaptations in long-term (>5 years) colorectal cancer survivors with ostomies. Thirty-three colorectal cancer survivors who participated in 8 gender- and health-related quality of life stratified focus groups and 130 colorectal cancer survivors who provided written comments to 2 open-ended questions on ostomy location and pouch problems participated in the study. Data were collected on health maintenance organization members in Oregon, southwestern Washington, and northern California. Qualitative data were analyzed for the 8 focus groups and written comments from 2 open-ended survey questions. Discussions from the focu s groups were recorded, transcribed, and analyzed using content analysis. Written content from the open-ended questions was derived from a mailed questionnaire on health-related quality of life in survivors with ostomies and analyzed using content analysis. Discussions related to persistent ostomy-related issues more than 5 years after formation were common. Persistent ostomy-related issues were focused on clothing restrictions and adaptations, dietary concerns, issues related to ostomy equipment and self-care, and the constant need to find solutions to adjust and readjust to living with an ostomy. Ostomy-specific concerns persist 5 years and more for long-term colorectal cancer survivors after initial ostomy formation. Adaptations tend to be individualized and based on trial and error. Findings underscore the need to develop long-term support mechanisms that survivors can access to promote better coping and adjustment to living with an ostomy.

  10. Long-term survival outcomes in patients with surgically treated oropharyngeal cancer and defined human papilloma virus status.

    Science.gov (United States)

    Dale, O T; Sood, S; Shah, K A; Han, C; Rapozo, D; Mehanna, H; Winter, S C

    2016-11-01

    This study investigated long-term survival outcomes in surgically treated oropharyngeal cancer patients with known human papilloma virus status. A case note review was performed of all patients undergoing primary surgery for oropharyngeal cancer in a single centre over a 10-year period. Human papilloma virus status was determined via dual modality testing. Associations between clinicopathological variables and survival were identified using a log-rank test. Of the 107 cases in the study, 40 per cent (n = 41) were human papilloma virus positive. The positive and negative predictive values of p16 immunohistochemistry for human papilloma virus status were 57 per cent and 100 per cent, respectively. At a mean follow up of 59.5 months, 5-year overall and disease-specific survival estimates were 78 per cent and 69 per cent, respectively. Human papilloma virus status (p = 0.014), smoking status (p = 0.021) and tumour stage (p = 0.03) were significant prognostic indicators. The long-term survival rates in surgically treated oropharyngeal cancer patients were comparable to other studies. Variables including human papilloma virus status and tumour stage were associated with survival in patients treated with primary surgery; however, nodal stage and presence of extracapsular spread were non-prognostic.

  11. How to Deal with Interval-Censored Data Practically while Assessing the Progression-Free Survival: A Step-by-Step Guide Using SAS and R Software.

    Science.gov (United States)

    Dugué, Audrey Emmanuelle; Pulido, Marina; Chabaud, Sylvie; Belin, Lisa; Gal, Jocelyn

    2016-12-01

    We describe how to estimate progression-free survival while dealing with interval-censored data in the setting of clinical trials in oncology. Three procedures with SAS and R statistical software are described: one allowing for a nonparametric maximum likelihood estimation of the survival curve using the EM-ICM (Expectation and Maximization-Iterative Convex Minorant) algorithm as described by Wellner and Zhan in 1997; a sensitivity analysis procedure in which the progression time is assigned (i) at the midpoint, (ii) at the upper limit (reflecting the standard analysis when the progression time is assigned at the first radiologic exam showing progressive disease), or (iii) at the lower limit of the censoring interval; and finally, two multiple imputations are described considering a uniform or the nonparametric maximum likelihood estimation (NPMLE) distribution. Clin Cancer Res; 22(23); 5629-35. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. Sex differences in lung cancer survival: long-term trends using population-based cancer registry data in Osaka, Japan.

    Science.gov (United States)

    Kinoshita, Fukuaki Lee; Ito, Yuri; Morishima, Toshitaka; Miyashiro, Isao; Nakayama, Tomio

    2017-09-01

    Several studies of sex differences in lung cancer survival have been reported. However, large-size population-based studies based on long-term observation are scarce. We investigated long-term trends in sex differences in lung cancer survival using population-based cancer registry data from Osaka, Japan. We analyzed 79 330 cases from the Osaka Cancer Registry (OCR) diagnosed between 1975 and 2007. We calculated 5-year relative survival in the six periods (1975-1980, 1981-1986, 1987-1992, 1993-1997, 1998-2002 and 2003-2007). To estimate the trends in sex differences in lung cancer survival throughout the study period, we applied a multivariate excess hazard model to control for confounders. The proportion of adenocarcinoma (ADC) and 5-year relative relative survival have increased for both sexes. Sex differences in lung cancer survival have widened over the period, especially in ADC and since the late 1990s. The excess hazard ratio of death within 5 years for males was 1.19 (95% CI: 1.16-1.21), adjusting for period at diagnosis, histologic type, stage, age group and treatment. We reported that females have better prognosis in lung cancer than males and the sex differences in lung cancer survival have become wider in Osaka, Japan. This can be partly explained by the sex differences in the proportions of histologic type and stage. Further studies considering other factors that influence sex differences in lung cancer survival are needed. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  13. Association Among Blood Transfusion, Sepsis, and Decreased Long-term Survival After Colon Cancer Resection.

    Science.gov (United States)

    Aquina, Christopher T; Blumberg, Neil; Becerra, Adan Z; Boscoe, Francis P; Schymura, Maria J; Noyes, Katia; Monson, John R T; Fleming, Fergal J

    2017-08-01

    To investigate the potential additive effects of blood transfusion and sepsis on colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival after colon cancer surgery. Perioperative blood transfusions are associated with infectious complications and increased risk of cancer recurrence through systemic inflammatory effects. Furthermore, recent studies have suggested an association among sepsis, subsequent systemic inflammation, and adverse cardiovascular outcomes. However, no study has investigated the association among transfusion, sepsis, and disease-specific survival in postoperative patients. The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I to III colon cancer resections from 2004 to 2011. Propensity-adjusted survival analyses assessed the association of perioperative allogeneic blood transfusion, sepsis, and 5-year colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival. Among 24,230 patients, 29% received a transfusion and 4% developed sepsis. After risk adjustment, transfusion and sepsis were associated with worse colon cancer disease-specific survival [(+)transfusion: hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.09-1.30; (+)sepsis: HR 1.84, 95% CI 1.44-2.35; (+)transfusion/(+)sepsis: HR 2.27, 95% CI 1.87-2.76], cardiovascular disease-specific survival [(+)transfusion: HR 1.18, 95% CI 1.04-1.33; (+)sepsis: HR 1.63, 95% CI 1.14-2.31; (+)transfusion/(+)sepsis: HR 2.04, 95% CI 1.58-2.63], and overall survival [(+)transfusion: HR 1.21, 95% CI 1.14-1.29; (+)sepsis: HR 1.76, 95% CI 1.48-2.09; (+)transfusion/(+)sepsis: HR 2.36, 95% CI 2.07-2.68] relative to (-)transfusion/(-)sepsis. Additional analyses suggested an additive effect with those who both received a blood transfusion and developed sepsis having even worse survival. Perioperative blood transfusions are associated with shorter survival

  14. Rich Medium Composition Affects Escherichia coli Survival, Glycation, and Mutation Frequency during Long-Term Batch Culture.

    Science.gov (United States)

    Kram, Karin E; Finkel, Steven E

    2015-07-01

    Bacteria such as Escherichia coli are frequently grown to high density to produce biomolecules for study in the laboratory. To achieve this, cells can be incubated in extremely rich media that increase overall cell yield. In these various media, bacteria may have different metabolic profiles, leading to changes in the amounts of toxic metabolites produced. We have previously shown that stresses experienced during short-term growth can affect the survival of cells during the long-term stationary phase (LTSP). Here, we incubated cells in LB, 2× yeast extract-tryptone (YT), Terrific Broth, or Super Broth medium and monitored survival during the LTSP, as well as other reporters of genetic and physiological change. We observe differential cell yield and survival in all media studied. We propose that differences in long-term survival are the result of changes in the metabolism of components of the media that may lead to increased levels of protein and/or DNA damage. We also show that culture pH and levels of protein glycation, a covalent modification that causes protein damage, affect long-term survival. Further, we measured mutation frequency after overnight incubation and observed a correlation between high mutation frequencies at the end of the log phase and loss of viability after 4 days of LTSP incubation, indicating that mutation frequency is potentially predictive of long-term survival. Since glycation and mutation can be caused by oxidative stress, we measured expression of the oxyR oxidative stress regulator during log-phase growth and found that higher levels of oxyR expression during the log phase are consistent with high mutation frequency and lower cell density during the LTSP. Since these complex rich media are often used when producing large quantities of biomolecules in the laboratory, the observed increase in damage resulting in glycation or mutation may lead to production of a heterogeneous population of plasmids or proteins, which could affect the

  15. Long term follow up study of survival associated with cleft lip and palate at birth

    DEFF Research Database (Denmark)

    Christensen, Kaare; Juel, K.; Herskind, Anne Maria

    2004-01-01

    OBJECTIVE: To assess the overall and cause specific mortality of people from birth to 55 years with cleft lip and palate. DESIGN: Long term follow up study. SETTING: Danish register of deaths. PARTICIPANTS: People born with cleft lip and palate between 1943 and 1987, followed to 1998. MAIN OUTCOME...... MEASURES: Observed and expected numbers of deaths, summarised as overall and cause specific standardised mortality ratios. RESULTS: 5331 people with cleft lip and palate were followed for 170 421 person years. The expected number of deaths was 259, but 402 occurred, corresponding to a standardised...... of death. CONCLUSIONS: People with cleft lip and palate have increased mortality up to age 55. Children born with cleft lip and palate and possibly other congenital malformations may benefit from specific preventive health measures into and throughout adulthood....

  16. Long-term survival and virulence of Mycobacterium leprae in amoebal cysts.

    Directory of Open Access Journals (Sweden)

    William H Wheat

    2014-12-01

    Full Text Available Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT, incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80% of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in

  17. Long-term survival and virulence of Mycobacterium leprae in amoebal cysts.

    Science.gov (United States)

    Wheat, William H; Casali, Amy L; Thomas, Vincent; Spencer, John S; Lahiri, Ramanuj; Williams, Diana L; McDonnell, Gerald E; Gonzalez-Juarrero, Mercedes; Brennan, Patrick J; Jackson, Mary

    2014-12-01

    Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA) can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80%) of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in human reservoirs

  18. Chemotherapy increases long-term survival in patients with adult medulloblastoma--a literature-based meta-analysis.

    Science.gov (United States)

    Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

    2016-03-01

    Adult medulloblastoma is a potentially curable malignant entity with an incidence of 0.5-1 per million. Valid data on prognosis, treatment, and demographics are lacking, as most current knowledge stems from retrospective studies. Surgical resection followed by radiotherapy are accepted parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification, and treatment of these patients were similar to previous cohorts. The median overall survival (mOS) was 65 months (95% CI: 54.6-75.3) , the 5-year overall survival was 50.9% with 16% of the patients dying more than 5 years after diagnosis. Incomplete resection, clinical and radiological signs for brainstem infiltration, and abstinence from radiotherapy were predictive of worse outcome. Metastatic disease at tumor recurrence was identified as a new prognostic factor, while neither metastasis at initial diagnosis nor desmoplastic/classic histology was correlated with survival. Patients receiving chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival and increases the proportion of patients with long-term survival. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions

  19. Important prognostic factors for the long-term survival of lung cancer subjects in Taiwan

    International Nuclear Information System (INIS)

    Chiang, Tai-An; Chen, Ping-Ho; Wu, Pei-Fen; Wang, Tsu-Nai; Chang, Po-Ya; Ko, Albert Min-Shan; Huang, Ming-Shyan; Ko, Ying-Chin

    2008-01-01

    This study used a large-scale cancer database in determination of prognostic factors for the survival of lung cancer subjects in Taiwan. Total of 24,910 subjects diagnosed with lung cancer was analysed. Survival estimates by Kaplan-Meier methods. Cox proportional-hazards model estimated the death risk (hazard ratio (HR)) for various prognostic factors. The prognostic indicators associated with a higher risk of lung cancer deaths are male gender (males versus females; HR = 1.07, 95% confidence intervals (CI): 1.03–1.11), males diagnosed in later periods (shown in 1991–1994 versus 1987–1990; HR = 1.13), older age at diagnosis, large cell carcinoma (LCC)/small cell carcinoma (SCC), and supportive care therapy over chemotherapy. The overall 5-year survival rate for lung cancer death was significantly poorer for males (21.3%) than females (23.6%). Subjects with squamous cell carcinoma (SQCC) and treatment by surgical resection alone had better prognosis. We find surgical resections to markedly increase 5-year survival rate from LCC, decreased risk of death from LCC, and no improved survival from SCC. Gender and clinical characteristics (i.e. diagnostic period, diagnostic age, histological type and treatment modality) play important roles in determining lung cancer survival

  20. Long-term survival among Hodgkin's lymphoma patients with gastrointestinal cancer: a population-based study

    Science.gov (United States)

    Youn, P.; Li, H.; Milano, M. T.; Stovall, M.; Constine, L. S.; Travis, L. B.

    2013-01-01

    Background The increased risk of gastrointestinal (GI) cancers after Hodgkin's lymphoma (HL) is well established. However, no large population-based study has described the actuarial survival after subsequent GI cancers in HL survivors (HL-GI). Patients and methods For 209 patients with HL-GI cancers (105 colon, 35 stomach, 30 pancreas, 21 rectum, and 18 esophagus) and 484 165 patients with first primary GI cancers (GI-1), actuarial survival was compared, accounting for age, gender, race, GI cancer stage, radiation for HL, and other variables. Results Though survival of HL patients who developed localized stage colon cancer was similar to that of the GI-1 group, overall survival (OS) of HL patients with regional or distant stage colon cancer was reduced [hazard ratio, (HR) = 1.46, P = 0.01]. The HL survivors with regional or distant stage colon cancer in the transverse segment had an especially high risk of mortality (HR: 2.7, P = 0.001 for OS). For localized stomach cancer, OS was inferior among HL survivors (HR = 3.46, P = 0.006). Conclusions The HL patients who develop GI cancer experience significantly reduced survival compared with patients with a first primary GI cancer. Further research is needed to explain the inferior survival of HL patients and to define selection criteria for cancer screening in HL survivors. PMID:22855552

  1. Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression-free survival: individual participant data analysis.

    Science.gov (United States)

    Franklin, Jeremy; Eichenauer, Dennis A; Becker, Ingrid; Monsef, Ina; Engert, Andreas

    2017-09-13

    Efficacy and the risk of severe late effects have to be well-balanced in treatment of Hodgkin lymphoma (HL). Late adverse effects include secondary malignancies which often have a poor prognosis. To synthesise evidence on the risk of secondary malignancies after current treatment approaches comprising chemotherapy and/or radiotherapy, we performed a meta-analysis based on individual patient data (IPD) from patients treated for newly diagnosed HL. We investigated several questions concerning possible changes in the risk of secondary malignancies when modifying chemotherapy or radiotherapy (omission of radiotherapy, reduction of the radiation field, reduction of the radiation dose, use of fewer chemotherapy cycles, intensification of chemotherapy). We also analysed whether these modifications affect progression-free survival (PFS) and overall survival (OS). We searched MEDLINE and Cochrane CENTRAL trials databases comprehensively in June 2010 for all randomised trials in HL since 1984. Key international trials registries were also searched. The search was updated in March 2015 without collecting further IPD (one further eligible study found) and again in July 2017 (no further eligible studies). We included randomised controlled trials (RCTs) for untreated HL patients which enrolled at least 50 patients per arm, completed recruitment by 2007 and performed a treatment comparison relevant to our objectives. Study groups submitted IPD, including age, sex, stage and the outcomes secondary malignant neoplasm (SMN), OS and PFS as time-to-event data. We meta-analysed these data using Petos method (SMN) and Cox regression with inverse-variance pooling (OS, PFS) for each of the five study questions, and performed subgroup and sensitivity analyses to assess the applicability and robustness of the results. We identified 21 eligible trials and obtained IPD for 16. For four studies no data were supplied despite repeated efforts, while one study was only identified in 2015 and IPD

  2. Audit in radiation therapy: long-term survival and cost of treatment

    International Nuclear Information System (INIS)

    Stevens, G.; Firth, I.

    1997-01-01

    In order to determine the cost of radiation treatment and the survival rate of a cohort of patients treated in a 6 month period in 1988, estimates of the capital and recurrent costs of this service were made for the calendar year 1988, expressed as $A(1988). Data collected prospectively included workload statistics (including number of attendances), field treated and complexity of treatment. Patient and tumour-related data included tumour site, intent of treatment and survival. The survival rate of patients during this period was determined in June 1995. The cost per field in 1988 was estimated at $A44.32. The 1988 costs of courses of definitive, adjuvant and palliative radiation therapy were estimated at $A2545, $A2482 and $A929, respectively. The major contributor to the cost of salaries and consumables within the Radiation Oncology Department (81.6%), with capital costs accounting for 13.5%, overheads accounting for 4.5% of the costs and planned admissions accounting for 0.2%. The median survival time of 580 patients with malignant disease treated during this period in 1988 was 12.4 months. The overall 5 year survival rate was 27%. For 105 patients treated definitively with radiation therapy, the median and 5 year survival rate figures were 26.0 months and 40%. For 149 patients treated with adjuvant radiation therapy, the 5 year survival rate was 62% (median survival rate not reached). For 279 patients treated palliatively, median and 5 year survival rate figures were 5.2 months and 3%. The cost per month of survival for all patients with malignancy was $A67; the figures for definitive , adjuvant and palliative treatments being $A74, $A48 and $A105, respectively. A sensitivity analysis indicated that these figures were robust. The cost of radiation treatment per field was comparable to reports for other centres and emphasizes the utility of radiation therapy as a cost-effective cancer treatment modality. 7 refs., 6 tabs., 2 figs

  3. Long-term survival in children with atrioventricular septal defect and common atrioventricular valvar orifice in Sweden.

    Science.gov (United States)

    Frid, Christina; Björkhem, Gudrun; Jonzon, Anders; Sunnegårdh, Jan; Annerén, Göran; Lundell, Bo

    2004-02-01

    The survival for patients with atrioventricular septal defect has improved markedly over the last decades and, during the same period, the survival of children with Down's syndrome has also increased. The aim of our study was to investigate long-term survival in patients having atrioventricular septal defect with common valvar orifice, but without associated significant congenital heart defects, in the setting of Down's syndrome, comparing the findings to those in chromosomally normal children with the same malformation. In a population-based retrospective study, we scrutinised the medical records from 801 liveborn children with atrioventricular septal defect born in Sweden during the period 1973 through 1997. Data on gender, presence or absence of Down's syndrome, associated congenital heart defects, date of birth, operation and death were recorded and followed up until 2001. An isolated atrioventricular septal defect with common atrioventricular valvar orifice was present in 502 children, of whom 86% had Down's syndrome. We found a significant reduc tion over time in age at operation, and in postoperative mortality at 30 days, from 28 to 1%. Using a multiple logistic regression model, we found no significant differences in mortality between genders, nor between those with or without Down's syndrome. Early corrective surgery could not be identified as a significant independent factor for survival. The 5-year postoperative survival in patients with Down's syndrome increased from 65% over the period from 1973 through 1977, to about 90% in the period 1993 through 1997, and the same trend was observed in chromosomally normal patients. Survival in uncomplicated atrioventricular septal defect with common atrioventricular valvar orifice has greatly increased, and surgical correction is now equally successful in patients with Down's syndrome and chromosomally normal patients, and for both genders. Death in connection with surgery is no longer the major threat, and focus

  4. 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.

  5. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  6. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    Science.gov (United States)

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-09

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Long-term weight loss after colorectal cancer diagnosis is associated with lower survival: The Colon Cancer Family Registry.

    Science.gov (United States)

    Kocarnik, Jonathan M; Hua, Xinwei; Hardikar, Sheetal; Robinson, Jamaica; Lindor, Noralane M; Win, Aung Ko; Hopper, John L; Figueiredo, Jane C; Potter, John D; Campbell, Peter T; Gallinger, Steven; Cotterchio, Michelle; Adams, Scott V; Cohen, Stacey A; Phipps, Amanda I; Newcomb, Polly A

    2017-12-01

    Body weight is associated with colorectal cancer (CRC) risk and survival, but to the authors' knowledge, the impact of long-term postdiagnostic weight change is unclear. Herein, the authors investigated whether weight change over the 5 years after a diagnosis of CRC is associated with survival. CRC cases diagnosed from 1997 to 2008 were identified through 4 population-based cancer registry sites. Participants enrolled within 2 years of diagnosis and reported their height and weight 2 years prior. Follow-up questionnaires were administered approximately 5 years after diagnosis. Associations between change in weight (in kg) or body mass index (BMI) with overall and CRC-specific survival were estimated using Cox regression analysis adjusted for age, sex, American Joint Committee on Cancer stage of disease, baseline BMI, nonsteroidal anti-inflammatory drug use, smoking, time between diagnosis and enrollment, and study site. At the 5-year postdiagnostic survey, 2049 participants reported higher (53%; median plus 5 kg), unchanged (12%), or lower (35%; median -4 kg) weight. Over a median of 5.1 years of subsequent follow-up (range, 0.3-9.9 years), 344 participants died (91 of CRC). Long-term weight loss (per 5 kg) was found to be associated with poorer overall survival (hazard ratio, 1.13; 95% confidence interval, 1.07-1.21) and CRC-specific survival (hazard ratio, 1.25; 95% confidence interval, 1.13-1.39). Significantly lower survival was similarly observed for relative weight loss (>5% vs ≤5% change), BMI reduction (per 1 unit), or BMI category change (overweight to normal vs remaining overweight). Weight loss 5 years after a diagnosis of CRC was found to be significantly associated with decreased long-term survival, suggesting the importance of avoiding weight loss in survivors of CRC. Future research should attempt to further evaluate this association, accounting for whether this weight change was intentional or represents a marker of declining health. Cancer 2017

  8. Sporulation and Germination patterns - hedging a bet on long term microbial survivability in dry soil

    Science.gov (United States)

    Claes, N.; Or, D.

    2012-04-01

    Soil hosts unparalleled diversity of microbial life that is constantly challenged by the vagaries of fluctuating ambient conditions. Desiccation stresses play a key role not only by directly affecting individual bacterial cells, but also by shaping diffusion pathways and cell dispersion. The gradual thinning and fragmentation of the aqueous environment during drying have led to different survival mechanisms including dormancy and sporulation, resulting in a highly resistive state capable of surviving extreme and prolonged environmental stresses until conditions improve in the future. Our aim is to investigate how temporal changes in hydration status shape microbial communities over time, based on simple survival strategy rules for each individual bacterium. The two survival strategies considered are dormancy and sporulation. Dormancy is the state in which bacterial cells significantly reduce their metabolism with minor morphological adaptations. The required energy and time for attaining this state are low relative to sporulation costs. Sporulation involves several morphological and biochemical changes that result in a resistive capsule that endures extreme stresses over long periods of time. The working hypothesis is that different micro-ecological conditions and community compositions would result from temporal patterns and magnitude of desiccation stresses. An Individual Based Model (IBM) considering habitats on rough soil surfaces and local effects of micro-hydrological conditions on dispersion and nutrient diffusion would enable systematic study of emerging communities over extended periods. Different population compositions are expected to emerge based on low and high frequency, duration and amplitudes of wetting-drying cycles reflecting relative success or failure of survival strategy.

  9. STAT3 Controls the Long-Term Survival and Phenotype of Repair Schwann Cells during Nerve Regeneration.

    Science.gov (United States)

    Benito, Cristina; Davis, Catherine M; Gomez-Sanchez, Jose A; Turmaine, Mark; Meijer, Dies; Poli, Valeria; Mirsky, Rhona; Jessen, Kristjan R

    2017-04-19

    After nerve injury, Schwann cells convert to a phenotype specialized to promote repair. But during the slow process of axonal regrowth, these repair Schwann cells gradually lose their regeneration-supportive features and eventually die. Although this is a key reason for the frequent regeneration failures in humans, the transcriptional mechanisms that control long-term survival and phenotype of repair cells have not been studied, and the molecular signaling underlying their decline is obscure. We show, in mice, that Schwann cell STAT3 has a dual role. It supports the long-term survival of repair Schwann cells and is required for the maintenance of repair Schwann cell properties. In contrast, STAT3 is less important for the initial generation of repair Schwann cells after injury. In repair Schwann cells, we find that Schwann cell STAT3 activation by Tyr705 phosphorylation is sustained during long-term denervation. STAT3 is required for maintaining autocrine Schwann cell survival signaling, and inactivation of Schwann cell STAT3 results in a striking loss of repair cells from chronically denervated distal stumps. STAT3 inactivation also results in abnormal morphology of repair cells and regeneration tracks, and failure to sustain expression of repair cell markers, including Shh, GDNF, and BDNF. Because Schwann cell development proceeds normally without STAT3, the function of this factor appears restricted to Schwann cells after injury. This identification of transcriptional mechanisms that support long-term survival and differentiation of repair cells will help identify, and eventually correct, the failures that lead to the deterioration of this important cell population. SIGNIFICANCE STATEMENT Although injured peripheral nerves contain repair Schwann cells that provide signals and spatial clues for promoting regeneration, the clinical outcome after nerve damage is frequently poor. A key reason for this is that, during the slow growth of axons through the proximal

  10. Long-term survival of two dogs after mitral valve plasty

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    Isamu Kanemoto

    2017-04-01

    Full Text Available Two small 9-year-old dogs received mitral valve plasty (MVP for severe mitral regurgitation that could not be controlled via drug administration. MVP consisted of chordal reconstruction using expanded polytetrafluoroethylene (ePTFE sutures and semicircular suture annuloplasty using polypropylene sutures. In both cases, the clinical signs dramatically improved after MVP, although postoperative echocardiography revealed slight residual mitral regurgitant flow. Both dogs survived for several years after MVP without any signs of cardiac distress; one dog survived for 9 years and 1 month, and the other dog survived for 7 years and 10 months. These findings highlight the durability of ePTFE sutures as artificial chordae and the excellence of semicircular suture annuloplasty in small dogs.

  11. Perioperative Mortality and Long-Term Survival in 80 Dogs and 32 Cats Undergoing Excision of Thymic Epithelial Tumors.

    Science.gov (United States)

    Garneau, Mark S; Price, Lori Lyn; Withrow, Stephen J; Boston, Sarah E; Ewing, Patty J; McClaran, Janet Kovak; Liptak, Julius M; Berg, John

    2015-07-01

    To examine perioperative mortality, long-term survival, causes of death, and prognostic factors for dogs and cats undergoing surgical excision of thymic epithelial tumors (TETs). Multi-institutional case series. Eighty dogs and 32 cats. Follow-up information was obtained for dogs and cats that underwent surgical excision of a TET between 2001 and 2012. Perioperative mortality was 20% in dogs and 22% in cats. No independent risk factors for perioperative mortality were identified. The estimated median survival time for all dogs was 1.69 years (95% CI 0.56-4.32) and the 1- and 4-year survival rates were 55% (95% CI 44-67) and 44% (95% CI 32-56). The estimated median survival time for all cats was 3.71 years (95% CI 0.56-unestimatable) and the 1- and 4-year survival rates were 70% (95% CI 53-87) and 47% (95% CI 0-100). Of animals that survived to discharge, 42% of dogs and 20% of cats eventually died of TET-related causes. The presence of paraneoplastic syndromes (hazard ratio [HR] 5.78, 95% CI 1.64-20.45, P = .007) or incomplete histologic margins (HR 6.09, 95% CI 1.50-24.72, P = .01) were independently associated with decreased survival in dogs. No significant predictors of survival were identified in cats. Conclusions regarding the effect of chemotherapy or radiation therapy could not be made. While there is substantial risk of perioperative death in dogs and cats undergoing surgery for TETs, many animals that survive to discharge have prolonged survival. Survival is significantly decreased in dogs with paraneoplastic syndromes or incomplete histologic margins. © Copyright 2014 by The American College of Veterinary Surgeons.

  12. Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation

    International Nuclear Information System (INIS)

    Slavin, S.; Strober, S.; Fuks, Z.; Kaplan, H.S.

    1976-01-01

    Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation, a procedure commonly used in the therapy of human malignant lymphomas, resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains (H-2/sup d/ and H-2/sup b/, respectively). Infusion of 10 7 (C57BL/Ka x Balb/c)F 1 bone marrow cells after total lymphoid irradiation further prolonged C57BL/Ka skin graft survival to more than 120 days. Total lymphoid irradiation may eventually prove useful in clinical organ transplantation

  13. PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons.

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    Alison Wood-Kaczmar

    2008-06-01

    Full Text Available Parkinson's disease (PD is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process. Although the pathogenesis of sporadic PD is unknown, the identification of the mendelian genetic factor PINK1 has provided new mechanistic insights. In order to investigate the role of PINK1 in Parkinson's disease, we studied PINK1 loss of function in human and primary mouse neurons. Using RNAi, we created stable PINK1 knockdown in human dopaminergic neurons differentiated from foetal ventral mesencephalon stem cells, as well as in an immortalised human neuroblastoma cell line. We sought to validate our findings in primary neurons derived from a transgenic PINK1 knockout mouse. For the first time we demonstrate an age dependent neurodegenerative phenotype in human and mouse neurons. PINK1 deficiency leads to reduced long-term viability in human neurons, which die via the mitochondrial apoptosis pathway. Human neurons lacking PINK1 demonstrate features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology. We report that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine. In addition we provide evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in PINK1 deficiency. The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD.

  14. Surviving the Holocaust: a meta-analysis of the long-term sequelae of a genocide.

    Science.gov (United States)

    Barel, Efrat; Van IJzendoorn, Marinus H; Sagi-Schwartz, Abraham; Bakermans-Kranenburg, Marian J

    2010-09-01

    The current set of meta-analyses elucidates the long-term psychiatric, psychosocial, and physical consequences of the Holocaust for survivors. In 71 samples with 12,746 participants Holocaust survivors were compared with their counterparts (with no Holocaust background) on physical health, psychological well-being, posttraumatic stress symptoms, psychopathological symptomatology, cognitive functioning, and stress-related physiology. Holocaust survivors were less well adjusted, as apparent from studies on nonselected samples (trimmed combined effect size d = 0.22, 95% CI [0.13, 0.31], N = 9,803) and from studies on selected samples (d = 0.45, 95% CI [0.32, 0.59], N = 2,943). In particular, they showed substantially more posttraumatic stress symptoms (nonselect studies: d = 0.72, 95% CI [0.46, 0.98], N = 1,763). They did not lag, however, much behind their comparisons in several other domains of functioning (i.e., physical health, stress-related physical measures, and cognitive functioning) and showed remarkable resilience. The coexistence of stress-related symptoms and good adaptation in some other areas of functioning may be explained by the unique characteristics of the symptoms of Holocaust survivors, who combine resilience with the use of defensive mechanisms. In most domains of functioning no differences were found between Israeli samples and samples from other countries. The exception was psychological well-being: For this domain it was found that living in Israel rather than elsewhere can serve as a protective factor. A biopsychological stress-diathesis model is used to interpret the findings, and future directions for research and social policy are discussed.

  15. Heparanase Expression in Malignant Salivary Gl, Tumors Inversely Correlates with Long-Term Survival

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    Ofer Ben-Izhak

    2006-10-01

    Full Text Available BACKGROUND: Upregulation of the endo-b-Dglucuronidase, heparanase, was noted in an increasing number of human malignancies. Heparanase expression correlated with enhanced local, distant metastatic spread, increased vascular density, reduced postoperative survival. PATIENTS, METHODS: We analyzed heparanase expression in 60 patients (aged 59 ± 17 years with malignant salivary tumors (39 males, 21 females using immunohistochemistry. We applied antiheparanase antibody 733, which has previously been shown to preferentially recognize a 50-kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining can directly be correlated with enzymatic activity. RESULTS: Heparanase staining was positive (> 0 in 70% of tumors (42 of 60 patients, was negative (0 in the remaining 30% (18 patients. The cumulative survival of patients diagnosed as heparanase-negative (n = 18 at 300 months was 70% (95% confidence interval = 35-88. In contrast, the cumulative survival of patients diagnosed as heparanase-positive (n = 42 at 300 months was 0% (statistically significant difference, P = .035. CONCLUSIONS: Heparanase expression levels inversely correlate with the survival rates of salivary gl, cancer patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy, an attractive target for anticancer drug development.

  16. Long-term survival of implantable cardioverter defibrillator recipients with end-stage renal disease

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    Mikhael F. El-Chami, MD, FACC, FHRS

    2017-10-01

    Conclusion: ESRD patients are at significantly increased risk of mortality as compared with a non-dialysis cohort. While the majority of these patients survive more than one year post-diagnosis, the three-year mortality is high (43%. Randomized studies addressing the benefits of ICDs in ESRD patients are needed to better define their value for primary prevention of SCD.

  17. Solar irradiance limits the long-term survival of Listeria monocytogenes in seawater.

    Science.gov (United States)

    NicAogáin, K; Magill, D; O'Donoghue, B; Conneely, A; Bennett, C; O'Byrne, C P

    2018-03-01

    Seafood has often been implicated in outbreaks of food-borne illness caused by Listeria monocytogenes but the source of contamination is usually not known. In this study we investigated the possibility that this pathogen could survive in seawater for an extended time period. Freshly collected seawater samples were inoculated with 1 × 10 8  CFU per ml of L. monocytogenes EGD-e and survival was monitored by plate counting for up to 25 days. When incubated in the dark, either at ambient temperatures (4-14°C) or at 16°C, >10 4  CFU per ml survivors were present after 25 days. However, when the seawater cell suspensions were exposed to ambient light (solar irradiation) and temperatures, L. monocytogenes lost viability rapidly and no survivors could be detected after the 80 h time point. Both UV-A and visible light in the blue region of the spectrum (470 nm) were found to contribute to this effect. The stress inducible sigma factor σ B was found to play a role in survival of L. monocytogenes in seawater. Together these data demonstrate that solar irradiation is a critical determinant of L. monocytogenes survival in marine environments. The data further suggest the possibility of controlling this food-borne pathogen in food-processing environments using visible light. Listeria monocytogenes is a food-borne bacterial pathogen capable of causing the life-threatening infection, listeriosis. In seafood the route of contamination from the environment is often not well understood as this pathogen is not generally thought to survive well in seawater. Here we provide evidence that L. monocytogenes is capable of surviving for long periods of time in seawater when light is excluded. Sunlight is demonstrated to have a significant effect on the survival of this pathogen in seawater, and both visible (470 nm) and UV-A light are shown to contribute to this effect. © 2017 The Society for Applied Microbiology.

  18. Lean body mass predicts long-term survival in Chinese patients on peritoneal dialysis.

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    Jenq-Wen Huang

    Full Text Available BACKGROUND: Reduced lean body mass (LBM is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD patients' outcomes and the factors related to increasing LBM are seldom reported. METHODS: We enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan-Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. RESULTS: Using the median LBM value (70% for men and 64% for women, patients were divided into group 1 (n = 52; low LBM and group 2 (n = 51; high LBM. Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p<0.05 and hospitalization (14.6 vs. 9.7/100 patient months; p<0.05. Group 1 patients also had shorter overall survival and technique survival (p<0.01. Each percentage point increase in LBM reduced the hazard ratio for mortality by 8% after adjustment for diabetes, age, sex, and body mass index (BMI. Changes in residual renal function and protein catabolic rate were independently associated with changes in LBM in the first year of PD. CONCLUSIONS: LBM serves as a good parameter in addition to BMI to predict the survival of patients on PD. Preserving residual renal function and increasing protein intake can increase LBM.

  19. Predictive factors of long-term colorectal cancer survival after ultrasound-controlled ablation of hepatic metastases.

    Science.gov (United States)

    Hernández-Socorro, Carmen Rosa; Saavedra, Pedro; Ramírez Felipe, José; Bohn Sarmiento, Uriel; Ruiz-Santana, Sergio

    2017-04-21

    The risk factors associated to long-term survival were assessed in patients with liver metastases of colorectal carcinoma undergoing ablative therapies. Single-centre cohort study, retrospectively analysed and prospectively collected consecutive patients with unresectable metastatic liver disease of colorectal carcinoma treated with ablative therapies between 1996 and 2013. Factors associated with survival time were identified using Cox's proportional hazard model with time-dependent covariates. A forward variable selection based on Akaike information criterion was performed. Relative risk and 95% confidence intervals for each factor were calculated. Statistical significance was set as P<.05. Seventy-five patients with liver metastases of colorectal cancer, with a mean age of 65.6 (10.3) underwent 106 treatments. Variables selected were good quality of life (RR 0.308, 95% CI 0.150-0.632) and tumour extension (RR 3.070, 95% CI 1.776-5.308). The median overall survival was 18.5 months (95% CI 17.4-24.4). The survival prognosis in median was 13.5 vs. 23.4 months for patients with and without tumour extension, and 23.0 vs. 12.8 months for patients with good and fair or poor quality of life, respectively. Good quality of life and tumour extension were the only statistically significant predictors of long-term survival in patients of colorectal carcinoma with liver metastatic disease undergoing ablative treatment with ultrasound. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  20. From Exit to Entry: Long-term Survival and Transmission of Salmonella

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    Landon L. Waldner

    2012-10-01

    Full Text Available Salmonella spp. are a leading cause of human infectious disease worldwide and pose a serious health concern. While we have an improving understanding of pathogenesis and the host-pathogen interactions underlying the infection process, comparatively little is known about the survival of pathogenic Salmonella outside their hosts. This review focuses on three areas: (1 in vitro evidence that Salmonella spp. can survive for long periods of time under harsh conditions; (2 observations and conclusions about Salmonella persistence obtained from human outbreaks; and (3 new information revealed by genomic- and population-based studies of Salmonella and related enteric pathogens. We highlight the mechanisms of Salmonella persistence and transmission as an essential part of their lifecycle and a prerequisite for their evolutionary success as human pathogens.

  1. Impact of obesity on long-term survival after aortic valve replacement with a small prosthesis.

    Science.gov (United States)

    Wang, Biao; Yang, Hongyang; Wang, Tao; Zhang, Xiquan; Zhu, Wenjie; Cao, Guangqing; Wu, Shuming

    2013-07-01

    Although many studies have evaluated the impact of obesity on various medical treatments, it is not known whether obesity is related to late mortality with implantation of small aortic prostheses. This study evaluated the effect of obesity on the late survival of patients after aortic valve replacement (AVR) with implantation of a small aortic prosthesis (size ≤ 21 mm). From January 1998 to December 2008, 307 patients in our institution who underwent primary AVR with smaller prostheses survived 30 days after surgery. Patients were categorized as normal weight if body mass index (BMI) was prosthesis. Obesity or/and overweight may also affect the NYHA classification, even in the longer term. EOAI should be improved where possible, as it may reduce late mortality and improve quality of life in obese or overweight patients.

  2. Intracranial tumors in infants: long-term functional outcome, survival, and its predictors.

    Science.gov (United States)

    Pillai, Shibu; Metrie, Mary; Dunham, Christopher; Sargent, Michael; Hukin, Juliette; Steinbok, Paul

    2012-04-01

    Intracranial tumors are rare in the first year of life. This study evaluates survival rates and functional outcomes of survivors at least 5 years after diagnosis and the predictors of this outcome. A retrospective chart review of all infants with a primary intracranial tumor was carried out. Radiology and pathology were re-reviewed. Outcome was assessed at 5 years or more after diagnosis using Bloom's categories (Bloom 1-2 = good outcome, the rest = poor outcome) and late effects severity scoring. Age, tumor location, size, extent of tumor resection, type of adjuvant therapy given, and WHO grade of tumor histology were evaluated as predictors of outcome. Among 35 infants, 20 (57%) survived, with 12 (34%) having a good outcome. Deficits among the survivors included neurological dysfunction in 14 (70%), visual impairment in 9 (45%), endocrine dysfunction in 5 (25%), and auditory disability in 3 (15%). Ten of the 20 survivors were either attending regular school or were engaged in a skilled job. At presentation, older age and an infratentorial location of the tumor are predictors of poor outcome. After histopathological diagnosis, the WHO grading of tumor is the only independent predictor of survival (p = 0.002) and functional outcome (p brain tumors (34%) had a good functional outcome and approximately a quarter of them (28%) were able to attend regular school or take up a skilled job. After tissue diagnosis, histological grade of tumor is the only independent predictor associated with outcome.

  3. Long term survival with whole abdominopelvic irradiation (WAI) in platinum-refractory ovarian cancer

    International Nuclear Information System (INIS)

    Cmelak, Anthony J.; Cox, Richard S.; Kapp, Daniel S.

    1996-01-01

    Purpose: To evaluate the efficacy and toxicity of WAI in persistent or recurrent epithelial ovarian carcinoma after initial chemotherapy. Methods and Materials: Between 1970 and 1995, 41 women with persistent or recurrent ovarian carcinoma after initial surgical debulking and chemotherapy were treated with WAI. Median age was 57 years (range 27-75). Initial FIGO stages were I and II - 5 patients (12%), III - 26 (64%), and IV - 10 (24%). Tumor grade was 1 - 4 (10%), II - 16 (39%), and III - 20 (49%). Four to eighteen (median eight) cycles of chemotherapy had been given prior to WAI. Thirty-one patients had received platinum-based regimens, and 22 of these had failed within six months after completion of chemotherapy (platinum-refractory). Prior to WAI, 11 (27%) patients had microscopic residual disease, 21 (51%) had gross residual disease up to 1.5 cm, and 9 (22%) had tumors greater than 1.5 cm in maximal diameter. Median doses of 28 Gy to the abdomen and 48 Gy to the pelvis were delivered using an open-field technique with appropriate liver and kidney shielding. Results: With follow-up of 1 month to 16.5 years, the 5-year actuarial disease specific survival was 47% in all 41 patients, and 49% in 22 platinum-refractory patients. Both disease bulk at WAI (p -4 ) and initial stage (p=0.005) were of prognostic value. Five-year disease specific survivals were stage I and II - 100%, stage III - 55%, and stage IV - 27%. Five-year disease specific survival of all nonbulky (less than 1.5 cm) patients was 40%; 0% for patients with disease greater than 1.5 cm. Five-year disease specific survival for grade I - 66%, II - 59%, and III - 33%. Stage I, II, or III patients with residual disease bulk of 1.5 cm or less before WAI had a 10-year actuarial disease specific survival of 50%. Twelve patients (29%) failed to complete the planned course of WAI due to acute toxicity (most often due to prolonged thrombocytopenia). Late bowel toxicity included obstruction in one patient and

  4. Long-term survival with repeat resection for lung oligometastasis from pancreatic ductal adenocarcinoma: a case report.

    Science.gov (United States)

    Matsuki, Ryota; Sugiyama, Masanori; Takei, Hidefumi; Kondo, Haruhiko; Fujiwara, Masachika; Shibahara, Junji; Furuse, Junji

    2018-03-27

    Long-term survival after resection of metastases from pancreatic ductal adenocarcinoma is rare. A 54-year-old man underwent pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) with UICC staging pT3N1M0 followed by adjuvant chemotherapy with gemcitabine (GEM). Three years after radical resection of the primary tumor, a tiny nodule was found in the lower lobe of the left lung. Despite treatment with GEM, it increased gradually, but no other metastases were found. Eighteen months after the first indication of the nodule, wedge resection was performed. Pathological examination of the nodule indicated a metastatic tumor from PDAC. Pulmonary metastasectomy was again performed for lung oligometastases at 77 and 101 months after PD. The patient has been asymptomatic without tumor recurrence for 4 years since the last pulmonary resection. In PDAC, the treatment strategy for oligometastasis is controversial. However, a few cases of long-term survival after pulmonary metastasectomy for oligometastasis of PDAC have been reported. More such cases need to be studied to address this issue effectively.

  5. Patterns of survival and volatile metabolites of selected Lactobacillus strains during long-term incubation in milk.

    Science.gov (United States)

    Łaniewska-Trokenheim, Łucja; Olszewska, Magdalena; Miks-Krajnik, Marta; Zadernowska, Anna

    2010-08-01

    The focus of this study was to monitor the survival of populations and the volatile compound profiles of selected Lactobacillus strains during long-term incubation in milk. The enumeration of cells was determined by both the Direct Epifluorescent Filter Technique using carboxyfluorescein diacetate (CFDA) staining and the plate method. Volatile compounds were analysed by the gas-chromatography technique. All strains exhibited good survival in cultured milks, but Lactobacillus crispatus L800 was the only strain with comparable growth and viability in milk, assessed by plate and epifluorescence methods. The significant differences in cell numbers between plate and microscopic counts were obtained for L. acidophilus strains. The investigated strains exhibited different metabolic profiles. Depending on the strain used, 3 to 8 compounds were produced. The strains produced significantly higher concentrations of acetic acid, compared to other volatiles. Lactobacillus strains differed from one another in number and contents of the volatile compounds.

  6. Impact of postoperative complications on readmission and long-term survival in patients following surgery for colorectal cancer.

    Science.gov (United States)

    Slankamenac, Ksenija; Slankamenac, Maja; Schlegel, Andrea; Nocito, Antonio; Rickenbacher, Andreas; Clavien, Pierre-Alain; Turina, Matthias

    2017-06-01

    It is well known that specific postoperative complications such as stroke influence readmissions and overall survival (OS) after surgery for colorectal cancer (CRC). Whether overall hospital morbidity is associated with increased risk of readmission and poorer long-term survival is unknown. New tools are available to accurately quantify overall morbidity, such as the comprehensive complication index (CCI). The aim is to evaluate the impact of complications on readmission and overall survival (OS) in patients operated for colorectal cancer. Postoperative complications of patients undergoing surgery for CRC were assessed over a 5-year period using the Clavien-Dindo classification, and overall morbidity was assessed by using the CCI. Individual scores were analyzed regarding their association with readmission and OS by using the multivariate logistic and Cox proportional-hazards regression analysis, respectively. Two hundred eighty-four patients were operated for CRC, of which 22 (8%) were readmitted. One hundred five patients (37%) developed at least one postoperative complication during the hospital stay. While single complications or the use of severe complication only (grade ≥IIIb) was not associated with readmission, overall morbidity (CCI) predicted readmission (OR 1.02 (95% CI 1.0-1.04), p = 0.044). Similarly, morbidity assessed by the CCI had a significant negative predictive value on OS, e.g., patients with a CCI of 20 were 22% more likely to die within a 5-year follow-up, when compared to patients with a CCI of 10 (p = 0.022). Overall combined morbidity as assessed by the CCI leads to more frequent readmission, and is associated with poorer long-term survival after surgery for CRC.

  7. The Effect of Novel Research Activities on Long-term Survival of Temporarily Captive Steller Sea Lions (Eumetopias jubatus.

    Directory of Open Access Journals (Sweden)

    Courtney Shuert

    Full Text Available Two novel research approaches were developed to facilitate controlled access to, and long-term monitoring of, juvenile Steller sea lions for periods longer than typically afforded by traditional fieldwork. The Transient Juvenile Steller sea lion Project at the Alaska SeaLife Center facilitated nutritional, physiological, and behavioral studies on the platform of temporary captivity. Temporarily captive sea lions (TJs, n = 35 were studied, and were intraperitoneally implanted with Life History Transmitters (LHX tags to determine causes of mortality post-release. Our goal was to evaluate the potential for long-term impacts of temporary captivity and telemetry implants on the survival of study individuals. A simple open-population Cormack-Jolly-Seber mark-recapture model was built in program MARK, incorporating resightings of uniquely branded study individuals gathered by several contributing institutions. A priori models were developed to weigh the evidence of effects of experimental treatment on survival with covariates of sex, age, capture age, cohort, and age class. We compared survival of experimental treatment to a control group of n = 27 free-ranging animals (FRs that were sampled during capture events and immediately released. Sex has previously been show to differentially affect juvenile survival in Steller sea lions. Therefore, sex was included in all models to account for unbalanced sex ratios within the experimental group. Considerable support was identified for the effects of sex, accounting for over 71% of total weight for all a priori models with delta AICc <5, and over 91% of model weight after removal of pretending variables. Overall, most support was found for the most parsimonious model based on sex and excluding experimental treatment. Models including experimental treatment were not supported after post-hoc considerations of model selection criteria. However, given the limited sample size, alternate models including effects of

  8. Superior long-term survival for fixed bearing compared with mobile bearing in ligament-balanced total knee arthroplasty.

    Science.gov (United States)

    Heesterbeek, P J C; van Houten, A H; Klenk, J S; Eijer, H; Christen, B; Wymenga, A B; Schuster, A J

    2018-05-01

    Only few long-term data on ligament-balanced cruciate-retaining total knee arthroplasty (CR TKA) are currently available. Either a mobile- or fixed-bearing insert can be chosen, which showed good mid-term outcome and few complications and revisions. This multi-centre retrospective cross-sectional cohort study investigated the 12-year results of primary TKA using a balancing gap technique and compared survival and clinical outcome between fixed and mobile inserts. In this retrospective cross-sectional cohort study, 557 cases of three clinics (2 Swiss, 1 Dutch) operated between 1998 and 2003 with the first series of a TKA implanted with a balanced gap technique (433 (77.7%) fixed, 124 (22.3%) mobile (anterior-posterior gliding (7-9 mm) and rotational (15°) degrees of freedom) inserts) were included for survival analysis (Kaplan-Meier, by insert type). At the 12-year follow-up (FU) examination of 189 cases, range of motion, knee society score (KSS), numeric rating scale (NRS) for pain and satisfaction were determined and radiographs were evaluated by median tests, by insert type. Of 521 cases available for analysis, 28 (5.4%; 11 fixed, 17 mobile bearing) were revised. Mean cumulative survival after 12.4 years was 97.0% (95% CI 94.7-98.4) for fixed bearings and 85.4% (95% CI 77.5-90.7) after 12.2 years for mobile bearings, p bearings. This study showed a superior survival for fixed bearing compared with mobile bearing in a CR TKA using a ligament-balanced technique after more than 12 years. Clinical outcomes are excellent to good after long-term follow-up, and similar for fixed and mobile bearing. Therapeutic studies-retrospective cohort study, Level III.

  9. Long-term survival of patients with multiple myeloma and acute renal failure at presentation.

    Science.gov (United States)

    Lazarus, H M; Adelstein, D J; Herzig, R H; Smith, M C

    1983-03-01

    Eight patients presented with simultaneous multiple myeloma and acute renal failure requiring hemodialysis. Patients had no known pre-existing renal disease nor exposure to nephrotoxic agents or x-ray contrast dye. Renal failure was attributed to light chain nephropathy in all cases. In 4 of these patients the diagnosis of myeloma was initially unsuspected. Renal biopsies in 3 of these patients, and post-mortem material in a fourth revealed the changes of "myeloma kidney." No patient regained renal function and all required chronic hemodialysis. Among these eight patients, three survived for periods greater than 21 months.

  10. Foraminiferal survival after long-term in situ experimentally induced anoxia

    Science.gov (United States)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-11-01

    Anoxia was successfully induced in four benthic chambers installed at 24 m depth on the northern Adriatic seafloor from 9 days to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerTM Green method was applied and calcareous and agglutinated foraminifera were analyzed. Numerous individuals were found living at all sampling times and at all sampling depths (to 5 cm), supported by a ribosomal RNA analysis that revealed that certain benthic foraminifera were active after 10 months of anoxia. The results show that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulfides. However, foraminiferal standing stocks decrease with sampling time in an irregular manner. A large difference in standing stock between two cores sampled under initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after one month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in cores sampled after 2 months of anoxia to then attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulfides but rather due to a continuous diminution of labile organic matter.

  11. Effects of moisture content on long-term survival and regrowth of bacteria in wastewater sludge

    Energy Technology Data Exchange (ETDEWEB)

    Yeager, J.G. (BDM Corp., Albuquerque, NM); Ward, R.L.

    1981-05-01

    The effects of moisture content on the survival and regrowth of seeded and indigenous enteric bacteria in raw sludge were determined. Cultures of six strains of fecally associated bacteria grown in sterilized, liquid sludge (5% solids) were all quite stable at this moisture level for over 90 days at 21/sup 0/C. When the moisture content of the sludge containing these organisms was reduced by evaporation and the samples were stored at 21/sup 0/C for extended periods, bacterial inactivation rates were generally proportional to the moisture losses of the samples. A dramatic reversal in this effect was observed in samples containing more than 90% solids. In this dried sludge, every bacterial species studied except Proteus mirabilis was found to be extremely stable. Bacteria indigenous to sludge were also found to survive for long periods in dried sludge. Growth of seeded Salmonella typhimurium was also found to occur in the presence of indigenous organisms in both liquid and dewatered raw sludges. However, the population density attained was well below that found in sterilized samples of the same sludges.

  12. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice.

    Science.gov (United States)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2016-06-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio. Copyright © 2016 the American Physiological Society.

  13. Effect Of Lymph Node Retrieval And Ratio On The Long-term Survival And Recurrence Of Colon Cancer

    International Nuclear Information System (INIS)

    Rao, A.; Dadras, M.; Razzak, M. A. A.; Ahmad, K.; Vijayasekar, C.

    2016-01-01

    Objective: To evaluate the association of lymph node retrieval and ratio with the prognosis of colon cancer. Study Design: A cohort study. Place and Duration of Study: Ninewells Hospital and Medical School, Dundee, UK, from October 2014 to March 2015. Methodology: Data was collected for adult patients who were diagnosed with primary adenocarcinoma of colon between 2003 and 2008. The follow-up period was 5-year. The data was collected from regional electronic colorectal cancer database. Kaplan-Meier graph was used to calculate and depict overall survival in different groups of patients. Result: There were a total of 370 patients with colon cancer. For Dukes stages A and B, there was no significant difference in median overall survival for patients with lymph node retrieval (< 12 nodes vs. > 12 nodes). For Dukes stage C (n=147), median survival for patients with lymph node retrieval < 12 nodes was 4 years vs. 4 years for patients with lymph node retrieval > 12 nodes (p = 0.85). Median survival for patients with lymph node ratio (LNR) < 0.125 was 4 years (range 1 - 11) vs. 3 years (range 0 - 11) for patients with LNR > 0.125 (p = 0.14). There was no significant difference in the recurrence rate based on lymph node retrieval (p = 0.87) and LNR (p = 0.97). Conclusion: Lymph node retrieval > 12 and reduced LNR < 0.125 had no significant effect on long-term survival and recurrence of colon cancer. (author)

  14. Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial.

    Science.gov (United States)

    Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

    2017-01-01

    Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied. The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients. Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders. The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283). The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

  15. Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

    DEFF Research Database (Denmark)

    Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

    2017-01-01

    Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently...... in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new Brd......U-positive neurons showed time-dependent attrition of ∼40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre-existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found...

  16. Gastric Endocrine Cell Carcinoma with Long-Term Survival Developing Metachronous Remnant Cancer

    Directory of Open Access Journals (Sweden)

    Tomoyuki Abe

    2011-04-01

    Full Text Available A rare case of primary gastric endocrine cell carcinoma in a 79-year-old man is reported. Upper gastrointestinal endoscopy showed a large Bormann’s type 2 tumour located in the middle of the stomach. On computed tomography, the gastric wall was thickened by the large tumour, and there were no distant metastases. Distal gastrectomy, lymph node dissection, and partial resection of the transverse colon were performed because the tumour involved the transverse mesocolon. The final pathological diagnosis was endocrine cell carcinoma, with tumour infiltration up to the subserous layer. Adjuvant chemotherapy was given, but metachronous remnant gastric cancer developed 2 years after surgery. Endoscopic submucosal dissection was performed for the early 0-IIc type gastric cancer, and the surgical margin was preserved. The patient has survived for 5 years after the primary surgery, remaining disease-free so far.

  17. Long-Term Survival and Risk of Second Cancers After Radiotherapy for Cervical Cancer

    International Nuclear Information System (INIS)

    Ohno, Tatsuya; Kato, Shingo; Sato, Shinichiro; Fukuhisa, Kenjiro; Nakano, Takashi; Tsujii, Hirohiko; Arai, Tatsuo

    2007-01-01

    Purpose: To evaluate the risk of second cancers after cervical cancer treated with radiotherapy for Asian populations. Methods and Materials: We reviewed 2,167 patients with cervical cancer undergoing radiotherapy between 1961 and 1986. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (12%). Relative risk (RR), absolute excess risk (AR), and cumulative risk of second cancer were calculated using the Japanese disease expectancy table. For 1,031 patients, the impact of smoking habit on the increasing risk of second cancer was also evaluated. Results: The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among the 2,167 patients, 1,063 (49%) survived more than 10 years. Second cancers were observed in 210 patients, representing a significant 1.2-fold risk (95% confidence interval [CI], 1.1-1.4) of developing second cancer compared with the general population, 1.6% excess risk per person per decade of follow-up, and elevating cumulative risk up to 23.8% (95% CI, 20.3-27.3) at 30 years after radiotherapy. The RR of second cancer was 1.6-fold for patients with the smoking habit and 1.4-fold for those without. Conclusions: Small but significant increased risk of second cancer was observed among Japanese women with cervical cancer mainly treated with high-dose rate brachytherapy. Considering the fact that about half of the patients survived more than 10 years, the benefit of radiotherapy outweighs the risk of developing second cancer

  18. Very long-term sequelae of craniopharyngioma.

    Science.gov (United States)

    Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

    2017-06-01

    Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

  19. Long-Term Survival of Dialysis Patients with Bacterial Endocarditis Undergoing Valvular Replacement Surgery in the United States

    Science.gov (United States)

    Leither, Maxwell D.; Shroff, Gautam R.; Ding, Shu; Gilbertson, David T.; Herzog, Charles A.

    2013-01-01

    Background Bacterial endocarditis in dialysis patients is associated with high mortality rates. The literature is limited regarding long-term outcomes of valvular replacement surgery and choice of prosthesis in dialysis patients with bacterial endocarditis. Methods and Results Dialysis patients hospitalized for bacterial endocarditis, 2004-2007, were studied retrospectively using data from the US Renal Data System. Long-term survival of patients undergoing valve replacement surgery with tissue or non-tissue valves was compared using the Kaplan-Meier method. A Cox proportional hazards model was used to identify independent predictors of mortality in patients undergoing valvular replacement surgery. During the study period, 11,156 dialysis patients were hospitalized for bacterial endocarditis and 1267 (11.4%) underwent valvular replacement surgery (tissue valve 44.3%, non-tissue valve 55.7%). In the valve replacement cohort, 60% were men, 50% white, 54% aged 45-64 years, and 36% diabetic. Estimated survival with tissue and non-tissue valves, respectively, at 0.5, 1, 2, and 3 years was 59% and 60%, 48% and 50%, 35% and 37%, and 25% and 30% (log rank P = 0.42). Staphylococcus was the predominant organism (66% of identified organisms). Independent predictors of mortality in patients undergoing valve replacement surgery included older age, diabetes as cause of end-stage renal disease, surgery during index hospitalization, staphylococcus as the causative organism, and dysrhythmias as a comorbid condition. Conclusions Valve replacement surgery is appropriate for well-selected dialysis patients with bacterial endocarditis, but is associated with high mortality rates. Survival does not differ with tissue or non-tissue prosthesis. PMID:23785002

  20. Ewing's sarcoma. Radiographic pattern of healing and bony complications in patients with long-term survival

    International Nuclear Information System (INIS)

    Ehara, S.; Kattapuram, S.V.; Egglin, T.K.

    1991-01-01

    The radiographic appearance of Ewing's sarcoma was studied retrospectively in 22 patients who survived 5 years or longer after diagnosis and treatment. Expected changes from treatment, including regression of the extraosseous soft tissue mass, periostitis, and reconstitution of the cortex, occurred in all patients. Local recurrence occurred in one patient 10 years after complete remission whereas secondary osteosarcoma occurred more than 5 years after complete remission in two other cases. Both recurrent and secondary tumors presented as new lytic foci at the site of the original primary lesion. Lytic changes from radiation (radiation osteitis) may develop more than 2 years after treatment and in this sample; such findings were widely distributed in the radiation port. The authors conclude that bone remodeling and postradiation changes occur slowly over 2 years after treatment, and that any localized lysis at the primary site is suspicious for recurrence or secondary neoplasm. Knowledge of the expected changes and patterns of local recurrence and secondary neoplasms helps one to detect any significant change in its early phase

  1. Pegylated liposomal doxorubicin in malignant pleural mesothelioma: a possible guardian for long-term survival

    Directory of Open Access Journals (Sweden)

    Zarogoulidis P

    2012-09-01

    Full Text Available Paul Zarogoulidis,1,2 Maria Mavroudi,1 Konstantinos Porpodis,1 Kalliopi Domvri,1 Antonios Sakkas,3 Nikolaos Machairiotis,1 Aikaterini Stylianaki,1 Anastasios Tsiotsios,1 Nikolaos Courcoutsakis,4 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Pulmonary Department-Interventional Unit, Ruhrland Klinik, University of Essen, Essen, Germany; 3Department of Pathology, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4Department of Radiology, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, GreeceAbstract: Malignant pleural mesothelioma is a rare and aggressive malignancy of the pleura correlated with exposure to asbestos, with a medium survival of 11–12 months after diagnosis. A case of a 67-year-old male who had previously worked in the asbestos industry and is a current smoker is reported. The computed tomography evaluation revealed a right pleural mass with pleural thickening, and the pleural biopsy confirmed a diagnosis of malignant pleural mesothelioma. He was treated with chemotherapy consisting of etoposide, paclitaxel, and pegylated liposomal doxorubicin hydrochloride. After completion of chemotherapy, radiologic evaluation confirmed a reduction of pleural thickening and improvement in his symptoms. A complete presentation of each drug formulation and characteristics are also included in this paper. The patient’s follow-up is continuing, and computed tomography reveals stable disease 9 years after initial examination.Keywords: mesothelioma, asbestos, pegylated liposomal doxorubicin

  2. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

    DEFF Research Database (Denmark)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even

    2016-01-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein....../sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our...... findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue...

  3. Long-term survival in elderly patients with a do-not-intubate order treated with noninvasive mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Riario-Sforza GG

    2011-04-01

    Full Text Available Paolo Scarpazza1, Cristoforo Incorvaia2, Paolo Amboni3, Giuseppe di Franco1, Stefania Raschi1, Pierfranco Usai1, Monica Bernareggi1, Cristiano Bonacina1, Chiara Melacini1, Roberta Cattaneo1, Serena Bencini1, Chiara Pravettoni2, Gian Galeazzo Riario-Sforza2, Gianni Passalacqua4, Walter Casali11Divisione di Broncopneumotisiologia, Ospedale Civile, Vimercate, Italy; 2Pulmonary Rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 3Clinical Chemistry Laboratory, Ospedali Riuniti, Bergamo, Italy; 4Allergy and Respiratory Diseases, University Of Genoa, Genoa, ItalyBackground: Noninvasive mechanical ventilation (NIMV is an effective tool in treating patients with acute respiratory failure (ARF, since it reduces both the need for endotracheal intubation and the mortality in comparison with nonventilated patients. A particular issue is represented by the outcome of NIMV in patients referred to the emergency department for ARF and with a do-not-intubate (DNI status because of advanced age or excessively critical conditions. This study evaluated long-term survival in a group of elderly patients with acute hypercapnic ARF who had a DNI order and who were successfully treated by NIMV.Methods: The population consisted of 54 patients with a favorable outcome after NIMV for ARF. They were followed up for 3 years by regular control visits, with at least one visit every 4 months, or as needed according to the patient’s condition. Of these, 31 continued NIMV at home and 23 were on long-term oxygen therapy (LTOT alone.Results: A total of 16 of the 52 patients had not survived at the 1-year follow-up, and another eight patients died during the 3-year observation, with an overall mortality rate of 30.8% after 1 year and 46.2% after 3 years. Comparing patients who continued NIMV at home with those who were on LTOT alone, 9 of the 29 patients on home NIMV died (6 after 1 year and 3 after 3 years and 15 of the 23 patients on LTOT alone died (10 after 1

  4. Long-term survival of transplanted allogeneic cells engineered to express a T cell chemorepellent.

    Science.gov (United States)

    Papeta, Natalia; Chen, Tao; Vianello, Fabrizio; Gererty, Lyle; Malik, Ashish; Mok, Ying-Ting; Tharp, William G; Bagley, Jessamyn; Zhao, Guiling; Stevceva, Liljana; Yoon, Victor; Sykes, Megan; Sachs, David; Iacomini, John; Poznansky, Mark C

    2007-01-27

    Alloantigen specific T cells have been shown to be required for allograft rejection. The chemokine, stromal cell derived factor-1 (SDF-1) at high concentration, has been shown to act as a T-cell chemorepellent and abrogate T-cell infiltration into a site of antigen challenge in vivo via a mechanism termed fugetaxis or chemorepulsion. We postulated that this mechanism could be exploited therapeutically and that allogeneic cells engineered to express a chemorepellent protein would not be rejected. Allogeneic murine insulinoma beta-TC3 cells and primary islets from BALB/C mice were engineered to constitutively secrete differential levels of SDF-1 and transplanted into allogeneic diabetic C57BL/6 mice. Rejection was defined as the permanent return of hyperglycemia and was correlated with the level of T-cell infiltration. The migratory response of T-cells to SDF-1 was also analyzed by transwell migration assay and time-lapse videomicroscopy. The cytotoxicity of cytotoxic T cell (CTLs) against beta-TC3 cells expressing high levels of SDF-1 was measured in standard and modified chromium-release assays in order to determine the effect of CTL migration on killing efficacy. Control animals rejected allogeneic cells and remained diabetic. In contrast, high level SDF-1 production by transplanted cells resulted in increased survival of the allograft and a significant reduction in blood glucose levels and T-cell infiltration into the transplanted tissue. This is the first demonstration of a novel approach that exploits T-cell chemorepulsion to induce site specific immune isolation and thereby overcomes allograft rejection without the use of systemic immunosuppression.

  5. Promoting long-term survival of insulin-producing cell grafts that differentiate from adipose tissue-derived stem cells to cure type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Shuzi Zhang

    Full Text Available BACKGROUND: Insulin-producing cell clusters (IPCCs have recently been generated in vitro from adipose tissue-derived stem cells (ASCs to circumvent islet shortage. However, it is unknown how long they can survive upon transplantation, whether they are eventually rejected by recipients, and how their long-term survival can be induced to permanently cure type 1 diabetes. IPCC graft survival is critical for their clinical application and this issue must be systematically addressed prior to their in-depth clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that IPCC grafts that differentiated from murine ASCs in vitro, unlike their freshly isolated islet counterparts, did not survive long-term in syngeneic mice, suggesting that ASC-derived IPCCs have intrinsic survival disadvantage over freshly isolated islets. Indeed, β cells retrieved from IPCC syngrafts underwent faster apoptosis than their islet counterparts. However, blocking both Fas and TNF receptor death pathways inhibited their apoptosis and restored their long-term survival in syngeneic recipients. Furthermore, blocking CD40-CD154 costimulation and Fas/TNF signaling induced long-term IPCC allograft survival in overwhelming majority of recipients. Importantly, Fas-deficient IPCC allografts exhibited certain immune privilege and enjoyed long-term survival in diabetic NOD mice in the presence of CD28/CD40 joint blockade while their islet counterparts failed to do so. CONCLUSIONS/SIGNIFICANCE: Long-term survival of ASC-derived IPCC syngeneic grafts requires blocking Fas and TNF death pathways, whereas blocking both death pathways and CD28/CD40 costimulation is needed for long-term IPCC allograft survival in diabetic NOD mice. Our studies have important clinical implications for treating type 1 diabetes via ASC-derived IPCC transplantation.

  6. The effect of retraining of nurses on cardiopulmonary resuscitationsuccess rate and short-term and long-term survival in patients revived

    Directory of Open Access Journals (Sweden)

    Dahi M

    2015-02-01

    Full Text Available Background and Objective: Cardiopulmonary resuscitation (CPR is performed in order to restore the functioning of two most important body organs the heart and brain. The present study was performed to investigate the effect of retraining of nurses on CPR success rate and short-term and long-term CPR survival. Materials and Method: The study population of the present quasi-experimental study consisted of all nurses of Taleghani Hospital affiliated with Shahid Beheshti University, Tehran, Iran, in 2011. The study subjects (n = 400 were selected using convenience and purposive sampling method. The patient survival rate during the first 24 hours (short-term survival and discharge from the hospital (long-term survival after CPR were reported. Then, the study subjects, in groups of 20, participated in CPR training courses. Short-term (24 hours and long-term (discharge from hospital in good mental status survival subsequent to CPR were reevaluated and compared with pre-training results. Data were analyzed using SPSS software version 20, and t-test and chi-square test. Results: Retraining promoted CPR success rates. This increase in the short-term success rate was not significant, but the increase in long-term success rate was statistically significant (P = 0.007. Conclusion: Periodic retraining of nurses may improve CPR success rate particularly long-term survival or discharge from hospital. Therefore, further studies on long-term success of CPR considering confounding factors are recommended

  7. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab.

    Science.gov (United States)

    McDermott, David F; Drake, Charles G; Sznol, Mario; Choueiri, Toni K; Powderly, John D; Smith, David C; Brahmer, Julie R; Carvajal, Richard D; Hammers, Hans J; Puzanov, Igor; Hodi, F Stephen; Kluger, Harriet M; Topalian, Suzanne L; Pardoll, Drew M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; McDonald, Dan; Sankar, Vindira; Sosman, Jeffrey A; Atkins, Michael B

    2015-06-20

    Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC. © 2015 by American Society of Clinical Oncology.

  8. Exposure to magnetic fields and long term survival among children having a leukemia; Exposition aux champs magnetiques et survie a long terme chez les enfants ayant une leucemie

    Energy Technology Data Exchange (ETDEWEB)

    Souques, M

    2006-09-15

    A study, the first one, bearing on the survival of children reached by acute lymphoblastic leukemia finds an association between mortality and the highest class of exposure ( over .3 {mu}T). The authors relativize the level of their results because the study has been made on a small number of cases, this illness staying rare. However, the relapse rate is not increased in a significant way for the children of the highest exposure category. (N.C.)

  9. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    International Nuclear Information System (INIS)

    Zeng, Jing; See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob; Durham, Nicholas; Meyer, Christian; Harris, Timothy J.; Albesiano, Emilia; Pradilla, Gustavo; Ford, Eric; Wong, John; Hammers, Hans-Joerg; Mathios, Dimitris; Tyler, Betty; Brem, Henry; Tran, Phuoc T.; Pardoll, Drew; Drake, Charles G.

    2013-01-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  10. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Durham, Nicholas [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Meyer, Christian [Department of Oncology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Harris, Timothy J. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Albesiano, Emilia; Pradilla, Gustavo [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Ford, Eric; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Hammers, Hans-Joerg [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Mathios, Dimitris; Tyler, Betty; Brem, Henry [Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); Pardoll, Drew; Drake, Charles G. [Department of Immunology, Johns Hopkins Medical Institutes, Baltimore, Maryland (United States); and others

    2013-06-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

  11. Long-term survival in pre-specified groups at risk in the Oslo Study, 1972-1973.

    Science.gov (United States)

    Holme, Ingar

    2015-03-01

    Using the Oslo Study of 1972-1973, we wished to compare the long-term mortality pattern up to 40 years, in both the healthy cardiovascular groups at supposedly high and low risk, and in some groups having cardiovascular disease at screening. At the screening, 16,203 (63% of those invited) men aged 40-49 years participated. Study groups were identified by means of questionnaires regarding diseases, blood pressure and measurements of total cholesterol, triglycerides and glucose. We identified six groups: very high cholesterol, very high blood pressure, very high glucose, non-smoking with non-elevated such risk factors, from a randomized diet and antismoking trial, and a randomized drug treatment in mild-to-moderate hypertension. Statistical analyses were by Cox regression analysis, with Kaplan-Meier graphs. The supposedly low-risk group had a total mortality of one-third of other groups, such as: men with hypertension, diabetes or hypercholesterolemia, or those whom participated in the two trials. Between these latter groups, we found 2-5 years of difference in their median survival time, but their absolute risk stayed at rather high levels through all the years, with the median remaining a lifetime that was 3-8 years shorter than the men whom were free of known cardiovascular disease, diabetes or hypertension. The long-term preventive effects on total mortality seem large, if the levels of the classical risk factors of blood pressure, total cholesterol and glucose can be adequately controlled, concurrently with a non-smoking behavior. The study indicated that non-smoking and a low total cholesterol value were the most important contributors to extended survival. © 2015 the Nordic Societies of Public Health.

  12. The role of radiotherapy in the treatment of childhood intracranial germinoma: long-term survival and late effects.

    Science.gov (United States)

    Strojan, Primoz; Zadravec, Lorna Zaletel; Anzic, Jozica; Korenjak, Roman; Jereb, Berta

    2006-07-01

    The aim of the present report was to evaluate the role of radiotherapy in the treatment of childhood intracranial germinoma in view of long-term survival and functional outcome. Nine children with histologically verified intracranial germinomas treated in Slovenia between 1983 and 1995 were reviewed. The four boys and five girls were 8.8-16.9 years old (median, 11.3 years). Five tumors were suprasellar, three were in the pineal region, and one patient had bifocal disease. Two patients had disseminated tumor. All patients received radiotherapy: six to the tumor bed, one to the whole brain, and two to the whole central nervous axis (CNA). The doses to the tumor bed ranged from 30 to 46 Gy (median, 44 Gy) and to the CNA were 24 and 34.5 Gy. Five patients received neoadjuvant cyclophosphamide and three patients, all with beta-human chorionic gonadotropin secreting tumors, received neoadjuvant cisplatin-based chemotherapy. Six patients are alive 12.8-21.8 years (median, 19 years) from diagnosis. The causes of death in three patients were disseminated disease, toxicity of salvage chemotherapy, and secondary etoposide-induced leukemia. All patients with suprasellar tumors presented with overt endocrinopathy. Results of psychological evaluation were subnormal in one out of five patients tested. Estimate of mental deterioration due to therapy ranged from 0% to 30% (median, 15%). Emotional disorder was registered in four patients and psycho-organic syndrome in three. Our results on long-term survival and functional outcome confirm the efficacy and relative safety of limited-field and reduced-dose radiotherapy for childhood intracranial germinoma when supplemented with chemotherapy. Copyright 2006 Wiley-Liss, Inc.

  13. Short-Term and Long-Term Survival and Virulence of Legionella pneumophila in the Defined Freshwater Medium Fraquil.

    Directory of Open Access Journals (Sweden)

    Nilmini Mendis

    Full Text Available Legionella pneumophila (Lp is the etiological agent responsible for Legionnaires' disease, a potentially fatal pulmonary infection. Lp lives and multiplies inside protozoa in a variety of natural and man-made water systems prior to human infection. Fraquil, a defined freshwater medium, was used as a highly reproducible medium to study the behaviour of Lp in water. Adopting a reductionist approach, Fraquil was used to study the impact of temperature, pH and trace metal levels on the survival and subsequent intracellular multiplication of Lp in Acanthamoeba castellanii, a freshwater protozoan and a natural host of Legionella. We show that temperature has a significant impact on the short- and long-term survival of Lp, but that the bacterium retains intracellular multiplication potential for over six months in Fraquil. Moreover, incubation in Fraquil at pH 4.0 resulted in a rapid decline in colony forming units, but was not detrimental to intracellular multiplication. In contrast, variations in trace metal concentrations had no impact on either survival or intracellular multiplication in amoeba. Our data show that Lp is a resilient bacterium in the water environment, remaining infectious to host cells after six months under the nutrient-deprived conditions of Fraquil.

  14. Evidence for the long-term stability of uranium mill tailings: survivability of ancient man-made earthern structures

    International Nuclear Information System (INIS)

    Lindsey, C.G.; Mishima, J.

    1982-09-01

    Pacific Northwest Laboratory (PNL), as part of a study for the Nuclear Regulatory Commission (NRC), is investigating long-term stabilization techniques for uranium mill tailings piles. Part of this invetigation involves the design of a rock armoring blanket to mitigate wind and water erosion of the underlying soil cover, which, in turn, prevents exposure of the tailings to the environment. However, the need for the armoring blanket, as well as this blanket's effectiveness, depends on the stability of the underlying soil cap (radon suppression cover) and on the tailings themselves. Compelling evidence in archaeological records suggests that large man-made earthen structures can remain sound and intact for time periods comparable to those required for the tailings piles. In this paper we present archaeological evidence of the existence and survivability of man-made earthen and rock structures through specific examples of such structures around the world. We also review factors contributing to the survival or destruction of these structures. Archaeological evidence suggests that whereas natural erosional forces have affected these structures, man's activities (e.g., agriculture, looting) have been the most damaging. The influence of climate, building materials, and construction techniques on survivability is addressed in this paper

  15. Does Off-Pump Coronary Artery Bypass Grafting Negatively Impact Long-Term Survival and Freedom from Reintervention?

    Directory of Open Access Journals (Sweden)

    Shahzad G. Raja

    2013-01-01

    Full Text Available Recently published evidence has raised concerns about worse late mortality and increasing need for reintervention after off-pump coronary artery bypass grafting. We undertook this study to assess the impact of off-pump coronary artery bypass grafting on survival and freedom from reintervention at 10 years. From January 2002 to December 2002, 307 consecutive patients who had isolated multivessel off-pump coronary artery bypass grafting at our institution were compared to a control group of 397 patients that underwent multivessel on-pump coronary artery bypass grafting during the same period. In addition, univariate and risk-adjusted comparisons between the two groups were performed at 10 years. Kaplan-Meier survival was similar for the two cohorts. After adjusting for clinical covariates, off-pump coronary artery bypass grafting did not emerge as a significant independent predictor of long-term mortality (Hazard Ratio 0.91; 95% Confidence Interval 0.70–1.12, readmission to hospital for cardiac cause (Hazard Ratio 0.96; 95% Confidence Interval 0.78–1.10, or the need for reintervention (Hazard Ratio 0.93; 95% Confidence Interval 0.87–1.05. Off-pump coronary artery bypass grafting compared with on-pump coronary artery bypass grafting does not adversely impact survival or freedom from reintervention at a 10-year follow-up.

  16. Cell-based neurotrophin treatment supports long-term auditory neuron survival in the deaf guinea pig.

    Science.gov (United States)

    Gillespie, Lisa N; Zanin, Mark P; Shepherd, Robert K

    2015-01-28

    The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the primary auditory neurons (ANs) of the cochlea. However, ANs degenerate in deafness; the preservation of a robust AN target population, in combination with advances in cochlear implant technology, may provide improved hearing outcomes for cochlear implant patients. The exogenous delivery of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 is well known to support AN survival in deafness, and cell-based therapies provide a potential clinically viable option for delivering neurotrophins into the deaf cochlea. This study utilized cells that were genetically modified to express BDNF and encapsulated in alginate microspheres, and investigated AN survival in the deaf guinea pig following (a) cell-based neurotrophin treatment in conjunction with chronic electrical stimulation from a cochlear implant, and (b) long-term cell-based neurotrophin delivery. In comparison to deafened controls, there was significantly greater AN survival following the cell-based neurotrophin treatment, and there were ongoing survival effects for at least six months. In addition, functional benefits were observed following cell-based neurotrophin treatment and chronic electrical stimulation, with a statistically significant decrease in electrically evoked auditory brainstem response thresholds observed during the experimental period. This study demonstrates that cell-based therapies, in conjunction with a cochlear implant, shows potential as a clinically transferable means of providing neurotrophin treatment to support AN survival in deafness. This technology also has the potential to deliver other therapeutic agents, and to be used in conjunction with other biomedical devices for the treatment of a variety of neurodegenerative conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Impact of Surgical Approach on Long-term Survival in Esophageal Adenocarcinoma Patients With or Without Neoadjuvant Chemoradiotherapy.

    Science.gov (United States)

    Noordman, Bo Jan; van Klaveren, David; van Berge Henegouwen, Mark I; Wijnhoven, Bas P L; Gisbertz, Suzanne S; Lagarde, Sjoerd M; van der Gaast, Ate; Hulshof, Maarten C C M; Biermann, Katharina; Steyerberg, Ewout W; van Lanschot, J Jan B

    2018-05-01

    To compare overall survival in patients with esophageal adenocarcinoma who underwent transhiatal esophagectomy (THE) with limited lymphadenectomy or transthoracic esophagectomy (TTE) with extended lymphadenectomy with or without neoadjuvant chemoradiotherapy (nCRT). The application of neoadjuvant therapy might change the association between the extent of lymphadenectomy and survival in patients with esophageal adenocarcinoma. This may influence the choice of surgical approach in patients treated with nCRT. Patients with potentially curable subcarinal esophageal adenocarcinoma treated with surgery alone or nCRT followed by surgery in 7 centers were included. The effect of surgical approach on overall survival, differentiated by the addition or omission of nCRT, was analyzed using a multivariable Cox regression model that included well-known prognostic factors and factors that might have influenced the choice of surgical approach. In total, 701 patients were included, of whom 318 had TTE with extended lymphadenectomy and 383 had THE with limited lymphadenectomy. TTE had differential effects on survival (P for interaction = 0.02), with a more favorable prognostic effect in patients who were treated with surgery alone [hazard ratio (HR) = 0.77, 95% confidence interval (CI) 0.58-1.03]. This association was statistically significant in a subgroup of patients with 1 to 8 positive lymph nodes in the resection specimen (HR = 0.62, 95% CI 0.43-0.90). The favorable prognostic effect of TTE over THE was absent in the nCRT and surgery group (HR = 1.16, 95% CI 0.80-1.66) and in the subgroup of nCRT patients with 1 to 8 positive lymph nodes in the resection specimen (HR = 1.00, 95% CI 0.61-1.68). Compared to surgery alone, the addition of nCRT may reduce the need for TTE with extended lymphadenectomy to improve long-term survival in patients with esophageal adenocarcinoma.

  18. A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

    Science.gov (United States)

    Haslem, Derrick S; Van Norman, S Burke; Fulde, Gail; Knighton, Andrew J; Belnap, Tom; Butler, Allison M; Rhagunath, Sharanya; Newman, David; Gilbert, Heather; Tudor, Brian P; Lin, Karen; Stone, Gary R; Loughmiller, David L; Mishra, Pravin J; Srivastava, Rajendu; Ford, James M; Nadauld, Lincoln D

    2017-02-01

    The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.

  19. Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis.

    Science.gov (United States)

    Winny, Markus; Paroglou, Vagia; Bektas, Hüseyin; Kaltenborn, Alexander; Reichert, Benedikt; Zachau, Lea; Kleine, Moritz; Klempnauer, Jürgen; Schrem, Harald

    2014-02-01

    This retrospective, single-center, observational study on postoperative long-term results aims to define yet unknown factors for long-term outcome after operation for chronic pancreatitis. We analyzed 147 consecutive patients operated for chronic pancreatitis from 2000 to 2011. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Complete long-term survival data were provided by the German citizen registration authorities for all patients. A quality-of-life questionnaire was sent to surviving patients after a mean follow-up of 5.7 years. Surgical principles were resection (n = 86; 59%), decompression (n = 29; 20%), and hybrid procedures (n = 32; 21%). No significant influences of different surgical principles and operative procedures on survival, long-term quality of life and pain control could be detected. Overall 30-day mortality was 2.7%, 1-year survival 95.9%, and 3-year survival 90.8%. Multivariate Cox regression analysis revealed that only postoperative insulin dependence at the time of hospital discharge (P = .027; Exp(B) = 2.111; 95% confidence interval [CI], 1.089-4.090) and the absence of pancreas enzyme replacement therapy at the time of hospital discharge (P = .039; Exp(B) = 2.102; 95% CI, 1.037-4.262) were significant, independent risk factors for survival with significant hazard ratios for long-term survival. Long-term improvement in quality of life was reported by 55 of 76 long-term survivors (73%). Pancreatic enzyme replacement should be standard treatment after surgery for chronic pancreatitis at the time of hospital discharge, even when no clinical signs of exocrine pancreatic failure exist. This study underlines the potential importance of early operative intervention in chronic pancreatitis before irreversible endocrine dysfunction is present. Copyright © 2014 Mosby, Inc. All rights reserved.

  20. The impact of combined pulmonary fibrosis and chronic obstructive pulmonary disease on long-term survival after lung cancer surgery.

    Science.gov (United States)

    Sekine, Yasuo; Sakairi, Yuichi; Yoshino, Mitsuru; Koh, Eitetsu; Hata, Atsushi; Suzuki, Hidemi; Yoshino, Ichiro

    2014-06-01

    The purpose of this study was to determine the impact of pulmonary fibrosis (PF) on postoperative complications and on long-term survival after surgical resection in lung cancer patients with chronic obstructive pulmonary disease (COPD). A retrospective chart review was conducted of 380 patients with COPD who had undergone pulmonary resection for lung cancer at the University Hospital between 1990 and 2005. The definition of COPD was a preoperative forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of less than 70%; PF was defined as obvious bilateral fibrous change in the lower lung fields, confirmed by computed tomography. PF was present in 41 patients (10.8%) with COPD; the remaining 339 patients (89.2%) did not have PF. The preoperative FVC/FEV1 was significantly lower in the group of patients with PF than in the group without (p < 0.05). Acute lung injury and home oxygen therapy were significantly more common in the PF group; however, the 30-day mortality was similar between the groups. The cumulative survival at 3 and 5 years was 53.6 and 36.9%, respectively, in the PF group and 71.4 and 66.1%, respectively, in the non-PF group (p = 0.0009). Increased age, decreased body mass index, advanced pathologic stage, and the existence of PF were identified as independent risk factors for decreased survival. PF is a risk factor for decreased survival after surgical treatment in lung cancer patients with COPD. Georg Thieme Verlag KG Stuttgart · New York.

  1. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    International Nuclear Information System (INIS)

    Boda-Heggemann, J.; Schneider, V.; Weiss, C.

    2013-01-01

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  2. Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Boda-Heggemann, J.; Schneider, V. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Radiation Oncology; Weiss, C. [Heidelberg Univ., Universitaetsmedizin Mannheim (Germany). Dept. of Biomathematics and Medical Statistics] [and others

    2013-05-15

    Purpose: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. Patients and methods: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Results: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. Conclusion: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity. (orig.)

  3. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

    Directory of Open Access Journals (Sweden)

    Marcos Perez-Basterrechea

    Full Text Available Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

  4. Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

    Science.gov (United States)

    Perez-Basterrechea, Marcos; Esteban, Manuel Martinez; Alvarez-Viejo, Maria; Fontanil, Tania; Cal, Santiago; Sanchez Pitiot, Marta; Otero, Jesus; Obaya, Alvaro Jesus

    2017-01-01

    Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

  5. Neuraxial anesthesia improves long-term survival after total joint replacement: a retrospective nationwide population-based study in Taiwan.

    Science.gov (United States)

    Chen, Wei-Hung; Hung, Kuo-Chuan; Tan, Ping-Heng; Shi, Hon-Yi

    2015-04-01

    This study explored the effects of general (GA) and neuraxial (NA) anesthesia on the outcomes of primary total joint replacement (TJR) in terms of postoperative mortality, length of stay (LOS), and hospital treatment costs. From 1997 to 2010, this nationwide population-based study retrospectively evaluated 7,977 patients in Taiwan who underwent primary total hip or knee replacement. We generated two propensity-score-matched subgroups, each containing an equal number of patients who underwent TJR with either GA or NA. Of the 7,977 patients, 2,990 (37.5%) underwent GA and 4,987 (62.5%) underwent NA. Propensity-score matching was used to create comparable GA and NA groups adjusted for age, sex, comorbidities, surgery type, hospital volume, and surgeon volume. Survival over the first three years following surgery was similar. The proportion of patients alive up to 14 years postoperatively for those undergoing NA was 58.2% (95% confidence interval [CI] 50.4 to 66.0), and for those undergoing GA it was 57.3% (95% CI 51.4 to 63.2). Neuraxial anesthesia was associated with lower median [interquartile range; IQR] hospital treatment cost ($4,079 [3,805-4,444] vs $4,113 [3,812-4,568]; P anesthesia costs are removed. The mechanism underlying the association between NA and long-term survival is unknown.

  6. First recovery in anorexia nervosa patients in the long-term course: a discrete-time survival analysis.

    Science.gov (United States)

    Herzog, W; Schellberg, D; Deter, H C

    1997-02-01

    The results of a 12-year follow-up study of occurrence and timing of first recovery in 69 hospitalized patients with severe anorexia nervosa (AN) are presented. For the first time discrete-time survival analysis methods were used to determine the likelihood of recovery in AN patients. Furthermore, predictors gleaned from pretreatment-posttreatment studies of long-term outcome in AN could be evaluated as to their effect on a change in the time course structure of the likelihood of first recovery. Results show that AN condition did not improve until after 6 years after the first inpatient treatment in 50% of patients. However, a restricter-type AN and low serum creatinine levels were predictors for earlier recovery. One specific effect was that AN patients who show purging behavior in combination with additional social disturbances have a lower chance of recovering. The use of discrete-time survival analysis methodology in further prospective studies will contribute to the development of more tailored treatment of AN, which also takes the individual phase of illness and specific aspects of the symptomatology into account.

  7. Long-term survival differences in gastric cancer after D2 lymphadenectomy and an improved assessment of resectability

    Directory of Open Access Journals (Sweden)

    Gabriel Dimofte

    2017-05-01

    Full Text Available Objective. The purpose of this work is to compare the long-term survival between a control group with mostly D1 lymphadenectomy and a study group with mostly D2 lymphadenectomy. Materials and Methods. We analyzed consecutive cases operated by a single surgeon performing mostly D2 lymphadenectomy and a control group of consecutive gastric cancer patients operated by a group of surgeons, performing mostly D1 lymphadenectomy, in a period when D2 lymphadenectomy was not the standard and was introduced as a new technique in our center. Results. We found 30,56% D2 lymphadenectomy in the control groups and 85,1% in the study group. At a five years interval from surgery the control group had no survivors, while the study group had 8 (20% survivors. Conclusions. The spleen and pancreas preserving D2 lymphadenectomy done by experienced surgeons, according to the current guidelines in order to select operable patients improves the overall survival of such gastric cancer patients.

  8. Molecular profiling of short-term and long-term surviving patients identifies CD34 mRNA level as prognostic for glioblastoma survival

    DEFF Research Database (Denmark)

    Michaelsen, Signe Regner; Urup, Thomas; Olsen, Lars Rønn

    2018-01-01

    Despite extensive treatment, overall survival (OS) for glioblastoma (GBM) remains poor. A small proportion of patients present long survival over 3 years, but the underlying molecular background separating these long-term survivors (LTS) from short-term survivors (STS) are insufficiently understood....... Accordingly, study aim was to identify independent prognostic biomarkers for survival. Study cohort consisted of 93 primary GBM patients treated with radiation-, chemo- and bevacizumab therapy, among which 14 STS (OS ≤ 12 months) and 6 LTS (OS ≥ 36 months) were identified, all confirmed being IDH wild......-type. RNA expression levels in diagnostic tumor specimen for 792 genes were analyzed by NanoString technology. While no differences were found with regard to GBM subtype between LTS versus STS, comparative analysis of individual genes identified 14 significantly differently expressed candidate genes...

  9. β2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Thompson, Philip A; O'Brien, Susan M; Xiao, Lianchun; Wang, Xuemei; Burger, Jan A; Jain, Nitin; Ferrajoli, Alessandra; Estrov, Zeev; Keating, Michael J; Wierda, William G

    2016-02-15

    A high pretreatment β2 -microglobulin (B2M) level is associated with inferior survival outcomes in patients with chronic lymphocytic leukemia. However, to the authors' knowledge, the prognostic and predictive significance of changes in B2M during treatment have not been reported to date. The authors analyzed 83 patients treated with ibrutinib-based regimens (66 with recurrent/refractory disease) and 198 treatment-naive patients who were treated with combined fludarabine, cyclophosphamide, and rituximab (FCR) to characterize changes in B2M and their relationship with clinical outcomes. B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib. On univariable analysis, normalization of B2M was associated with superior progression-free survival (PFS) from the 6-month landmark in patients treated with ibrutinib-based regimens and FCR. On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p). In contrast, in patients treated with FCR, negative minimal residual disease status in the bone marrow was the only variable found to be significantly associated with superior PFS (hazard ratio, 0.28; 95% CI, 0.12-0.67 [P = .004]). Normalization of B2M at 6 months in patients treated with ibrutinib was found to be a useful predictor of subsequent PFS and may assist in clinical decision-making. © 2015 American Cancer Society.

  10. Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL

    Energy Technology Data Exchange (ETDEWEB)

    Mikhaeel, N.G.; Smith, Daniel [Guy' s and St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London (United Kingdom); Dunn, Joel T.; Phillips, Michael; Barrington, Sally F. [King' s College London, PET Imaging Centre at St Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Moeller, Henrik [King' s College London, Department of Cancer Epidemiology and Population Health, London (United Kingdom); Fields, Paul A.; Wrench, David [Guy' s and St Thomas' NHS Foundation Trust, Department of Haematology, London (United Kingdom)

    2016-07-15

    The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm{sup 3}. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur. (orig.)

  11. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    International Nuclear Information System (INIS)

    Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

    2010-01-01

    Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

  12. Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

    Science.gov (United States)

    Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

    2017-01-01

    Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

  13. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    Science.gov (United States)

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. Pre- and Posttransplant IgA Anti-Fab Antibodies to Predict Long-term Kidney Graft Survival.

    Science.gov (United States)

    Amirzargar, M A; Amirzargar, A; Basiri, A; Hajilooi, M; Roshanaei, G; Rajabi, G; Solgi, G

    2015-05-01

    Immunologic factors are reliable markers for allograft monitoring, because of their seminal role in rejection process. One of these factors is the immunoglobulin (Ig)A anti-Fab of the IgG antibody. This study aimed to evaluate the predictive value of pre- and posttransplant levels of this marker for kidney allograft function and survival. Sera samples of 59 living unrelated donor kidney recipients were collected before and after transplantation (days 7, 14, and 30) and investigated for IgA anti-Fab of IgG antibody levels using enzyme-linked immunosorbent assay in relation with allograft outcome. Among 59 patients, 15 cases (25%) including 10 with acute rejection and 5 with chronic rejection episodes showed graft failure during a mean of 5 years of follow-up. High posttransplant levels of IgA anti-Fab antibodies were observed more frequently in patients with stable graft function (SGF) compared with patients with graft failure (P = 2 × 10(-6)). None of patients with acute or chronic rejection episodes had high levels of IgA anti-Fab antibodies at day 30 posttransplant compared with the SGF group (P = 10(-6) and P = .01, respectively). In addition, high levels of IgA anti-Fab antibody correlated with lesser concentration of serum creatinine at 1 month posttransplantation (P = .01). Five-year graft survival was associated with high levels of pre- and posttransplant IgA anti-Fab antibodies (P = .02 and P = .003, respectively). Our findings indicate the protective effect of higher levels of IgA anti-Fab antibodies regarding to kidney allograft outcomes and long-term graft survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Impact of treatment in long-term survival patients with follicular lymphoma: A Spanish Lymphoma Oncology Group registry

    Science.gov (United States)

    Provencio, Mariano; Sabín, Pilar; Gomez-Codina, Jose; Calvo, Virginia; Llanos, Marta; Gumá, Josep; Quero, Cristina; Blasco, Ana; Cruz, Miguel Angel; Aguiar, David; García-Arroyo, Francisco; Lavernia, Javier; Martinez, Natividad; Morales, Manuel; Saez-Cusi, Alvaro; Rodriguez, Delvys; de la Cruz, Luis; Sanchez, Jose Javier; Rueda, Antonio

    2017-01-01

    Background Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe. However, most of the prospective randomized studies have very little follow-up compared to the long natural history of the disease. The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma. Patients and methods A total of 1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were prospectively enrolled from 1980 to 2013. Results Median follow-up was 54.9 months and median overall survival is over 20 years in our series. We analyzed the patients who are still alive beyond 10 years from diagnosis in order to fully assess the prognostic factors that condition this group. Out of 166 patients who are still alive after more than 10 years of follow-up, 118 of them (73%) are free of evident clinical disease. Variables significantly associated with survival at 10 years were stage < II (p <0.03), age < 60 years (p <0.0001), low FLIPI (p <0.002), normal β2 microglobulin (p <0.005), no B symptoms upon diagnosis (p <0.02), Performance Status 0–1 (p <0.03) and treatment with anthracyclines and rituximab (p <0.001), or rituximab (p <0.0001). Conclusions A longer follow-up and a large series demonstrated a substantial population of patients with follicular lymphoma free of disease for more than 10 years. PMID:28493986

  16. Long-term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer.

    Science.gov (United States)

    Shrestha, Bikram; Sun, Yifei; Faisal, Farzana; Kim, Victoria; Soares, Kevin; Blair, Alex; Herman, Joseph M; Narang, Amol; Dholakia, Avani S; Rosati, Lauren; Hacker-Prietz, Amy; Chen, Linda; Laheru, Daniel A; De Jesus-Acosta, Ana; Le, Dung T; Donehower, Ross; Azad, Nilofar; Diaz, Luis A; Murphy, Adrian; Lee, Valerie; Fishman, Elliot K; Hruban, Ralph H; Liang, Tingbo; Cameron, John L; Makary, Martin; Weiss, Matthew J; Ahuja, Nita; He, Jin; Wolfgang, Christopher L; Huang, Chiung-Yu; Zheng, Lei

    2017-07-01

    The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL-PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL-PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL-PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13-0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19-0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long-term survival in a subpopulation of patients with BL-PDAC. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

    Science.gov (United States)

    Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

    2015-01-01

    In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

  18. Association of High-Dose Ibuprofen Use, Lung Function Decline, and Long-Term Survival in Children with Cystic Fibrosis.

    Science.gov (United States)

    Konstan, Michael W; VanDevanter, Donald R; Sawicki, Gregory S; Pasta, David J; Foreman, Aimee J; Neiman, Evgueni A; Morgan, Wayne J

    2018-04-01

    .04) during the corresponding 2-year period, a 37.5% slower decline among users compared with nonusers (95% confidence interval; 0.4%, 71.3%; P = 0.046). The users had better subsequent survival (P cystic fibrosis, we observed an association between high-dose ibuprofen use and both slower lung function decline and improved long-term survival. These results are consistent with the hypothesis that treatment-associated reduction of lung function decline in children with cystic fibrosis leads to improved survival.

  19. Impact of perioperative liver dysfunction on in-hospital mortality and long-term survival in infective endocarditis patients.

    Science.gov (United States)

    Diab, M; Sponholz, C; von Loeffelholz, C; Scheffel, P; Bauer, M; Kortgen, A; Lehmann, T; Färber, G; Pletz, M W; Doenst, T

    2017-12-01

    Infective endocarditis (IE) is often associated with multiorgan dysfunction and mortality. The impact of perioperative liver dysfunction (LD) on outcome remains unclear and little is known about factors leading to postoperative LD. We performed a retrospective, single-center analysis on 285 patients with left-sided IE without pre-existing chronic liver disease referred to our center between 2007 and 2013 for valve surgery. Sequential organ failure assessment (SOFA) score was used to evaluate organ dysfunction. Chi-square, Cox regression, and multivariate analyses were used for evaluation. Preoperative LD (Bilirubin >20 μmol/L) was present in 68 of 285 patients. New, postoperative LD occurred in 54 patients. Hypoxic hepatitis presented the most common origin of LD, accompanied with high short-term mortality. In-hospital mortality was higher in patients with preoperative and postoperative LD compared to patients without LD (51.5, 24.1, and 10.4%, respectively, p endocarditis is an independent predictor of short- and long-term mortalities. After surviving the hospital stay, 5-year prognosis is not different and quality of life is not affected by LD. S. aureus and duration of cardiopulmonary bypass represent risk factors for postoperative LD.

  20. Predicting short-term mortality and long-term survival for hospitalized US patients with alcoholic hepatitis.

    Science.gov (United States)

    Cuthbert, Jennifer A; Arslanlar, Sami; Yepuri, Jay; Montrose, Marc; Ahn, Chul W; Shah, Jessica P

    2014-07-01

    No study has evaluated current scoring systems for their accuracy in predicting short and long-term outcome of alcoholic hepatitis in a US population. We reviewed electronic records for patients with alcoholic liver disease (ALD) admitted to Parkland Memorial Hospital between January 2002 and August 2005. Data and outcomes for 148 of 1,761 admissions meeting pre-defined criteria were collected. The discriminant function (DF) was revised (INRdf) to account for changes in prothrombin time reagents that could potentially affect identification of risk using the previous DF threshold of >32. Admission and theoretical peak scores were calculated by use of the Model for End-stage Liver Disease (MELD). Analysis models compared five different scoring systems. INRdf was closely correlated with the old DF (r (2) = 0.95). Multivariate analysis of the data showed that survival for 28 days was significantly associated with a scoring system using a combination of age, bilirubin, coagulation status, and creatinine (p short-term mortality (p 50 % mortality at four weeks and >80 % mortality at six months without specific treatment.

  1. Older patients with inoperable non-small cell lung cancer. Long-term survival after concurrent chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Semrau, Sabine; Fietkau, Rainer [Friedrich-Alexander-University Erlangen-Nuernberg, Department of Radiation Oncology, Erlangen (Germany); Zettl, Heike [Rostock Cancer Registry University of Rostock, Rostock (Germany); Hildebrandt, Guido [University of Rostock, Department of Radiation Therapy, Rostock (Germany); Klautke, Gunther [Klinikum Chemnitz, Department of Radiation Therapy, Chemnitz (Germany)

    2014-12-15

    Considering the various comorbidities associated with aging, the feasibility and usefulness of concurrent chemoradiotherapy (CRT) in older patients with inoperable non-small cell lung cancer (NSCLC) is a controversial issue. Here, we compared the feasibility of CRT and the effects of various comorbidities on the prognosis of a minimally selected population of inoperable NSCLC patients aged 60-77 years. The study comprised 161 patients with inoperable NSCLC who received CRT with a target radiation dose greater than 60 Gy and platinum-based chemotherapy from 1998 to 2007. The total population included 69 patients aged 60-69 years and 53 aged 70-77 years. These two age cohorts were included in the study with a follow-up of a median 14.5 months. The two groups showed no differences in long-term survival, as reflected by the 5-year survival rates of 13.0 ± 4.1 % (60- to 69-year-olds) and 14.4 ± 4.9 % (70- to 77-year-olds). During the treatment phase, the groups were comparable in terms of toxicity and the feasibility of chemotherapy. Compared to patients in their 60s, the septuagenarians had more pulmonary comorbidities (p = 0.02), diabetes mellitus (p = 0.04), cardiac comorbidities (p = 0.08), and previous cancer disease (p = 0.08) that exerted a negative effect on survival. In patients without comorbidities, there were no differences between the age groups. Age is not a contraindication for concurrent CRT per se, because elderly patients do not have a worse long-term prognosis than younger seniors. However, ''elderly patients'' (≥ 70-77 years) have more concomitant diseases associated with shorter survival than ''moderately aged patients'' (≥ 60-69 years). (orig.) [German] Hinsichtlich der verschiedenen altersbedingten Komorbiditaeten werden die Durchfuehrbarkeit und der Nutzen einer simultanen Chemoradiotherapie (''concurrent chemoradiotherapy'', CRT) bei alten Patienten mit einem inoperablen nicht

  2. Atypical clinical presentation and long-term survival in a patient with optic nerve medulloepithelioma: a case report

    Directory of Open Access Journals (Sweden)

    Pastora-Salvador Natalia

    2012-05-01

    Full Text Available Abstract Introduction Medulloepithelioma is a rare congenital tumor of the primitive medullary neuroepithelium. A significant proportion of patients with medulloepithelioma arising from the optic nerve die from intracranial spread or cerebral metastasis. Because it has no known distinct clinical features and because of its low frequency, this tumor presents within the first two to six years of life and is usually misdiagnosed clinically as a different type of optic nerve tumor. Here, we describe a new and atypical case of medulloepithelioma of the optic nerve in a 12-year-old boy. To the best of our knowledge, he is the oldest reported patient to present with this disease and, now as an adult, has the longest documented period of disease-free survival. Case presentation A 12-year-old Caucasian boy with headache and unilateral amaurosis was referred for a presumed optic nerve glioma to our hospital. A computed tomography scan showed optic nerve enlargement, and fundoscopy showed a whitish mass at the optic disc. Our patient had been followed at his local hospital for four years for an 'optic disc cyst' with no change or progression. He experienced mild progressive visual impairment during that period. He was admitted for resection, and a histopathological analysis revealed a medulloepithelioma of the optic nerve. Supplemental orbital radiotherapy was performed. He remained disease-free for 25 years. Conclusions Medulloepithelioma of the optic nerve can clinically mimic more common pediatric tumors, such as optic glioma, meningioma, or retinoblastoma. Thus, medulloepithelioma should be included in the differential diagnoses of pediatric optic nerve lesions. Fundoscopy in these patients may provide relevant information for diagnosis. Anterior optic nerve medulloepitheliomas may behave differently from and have a better prognosis than medulloepitheliomas that have a more posterior location. Our case report illustrates that long-term survival can be

  3. Case report: long-term survival of an infant syndromic patient affected by atypical teratoid-rhabdoid tumor

    International Nuclear Information System (INIS)

    Modena, Piergiorgio; Maestro, Roberta; Giangaspero, Felice; Massimino, Maura; Sardi, Iacopo; Brenca, Monica; Giunti, Laura; Buccoliero, Anna Maria; Pollo, Bianca; Biassoni, Veronica; Genitori, Lorenzo; Antonelli, Manila

    2013-01-01

    Atypical teratoid rhabdoid tumor (ATRT) patients display a dismal median overall survival of less than 1 year. A consistent fraction of cases carries de-novo SMARCB1/INI1 constitutional mutations in the setting of the “rhabdoid tumor predisposition syndrome” and the outcome is worst in infant syndromic ATRT patients. We here describe a patient affected by mosaic Klinefelter syndrome and by rhabdoid tumor predisposition syndrome caused by constitutional SMARCB1/INI1 heterozygous mutation c.118C>T (Arg40X). Patient’s ATRT primary tumor occurred at 2 years of age concurrent with metastatic lesions. The patient was rendered without evidence of disease by combined surgery, high-dose poli-chemotherapy and craniospinal irradiation, followed by autologous hematopoietic stem cell transplantation. At the onset of a spinal lesion 5.5 years later, both tumors were pathologically and molecularly evaluated at the national central pathology review board and defined as ATRT in a syndromic patient, with strong evidence of a clonal origin of the two lesions. The patient was then treated according to SIOP guidelines and is now alive without evidence of disease 24 months after the detection of metastatic disease and 90 months after the original diagnosis. The report underscores the current utility of multiple comprehensive approaches for the correct diagnosis and clinical management of patients affected by rare and atypical brain neoplasms. Successful local control of disease and achievement of long-term survival is possible in ATRT patients even in the setting of rhabdoid tumor predisposition syndrome, infant age at diagnosis and metastatic spread of disease, thus justifying the efforts for the management of this severe condition

  4. Rituximab-containing reduced-intensity conditioning improves progression-free survival following allogeneic transplantation in B cell non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Narendranath Epperla

    2017-06-01

    Full Text Available Abstract Background In B cell non-Hodgkin lymphoma (B-NHL, rituximab-containing reduced-intensity conditioning regimens (R-RIC have been shown to provide favorable outcomes in single-arm studies; however, large multicenter studies comparing R-RIC and non-rituximab-containing reduced-intensity conditioning regimens (nonR-RIC have not been performed. Using the CIBMTR database, we report the outcomes of R-RIC versus nonR-RIC regimens in B-NHL. Methods We evaluated 1401 adult B-NHL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT who received nonR-RIC (n = 1022 or R-RIC (n = 379 regimens. Graft-versus-host disease (GVHD prophylaxis was limited to calcineurin inhibitor-based approaches. Results Median follow-up of survivors in the R-RIC and nonR-RIC groups was 47 and 37 months, respectively. On multivariate analysis, no difference was seen between the R-RIC and nonR-RIC cohorts in terms of acute GVHD grade II–IV (RR = 1.14, 95%CI = 0.83–1.56, p = 0.43 or grade III–IV (RR = 1.16, 95%CI = 0.72–1.89, p = 0.54, chronic GVHD (RR = 1.15, 95%CI = 0.92–1.46, p = 0.22, non-relapse mortality (RR = 0.90; 95%CI = 0.67–1.22; p = 0.51, relapse/progression (RR = 0.79; 95%CI = 0.63–1.01; p = 0.055, and mortality (RR = 0.84, 95%CI = 0.69–1.02, p = 0.08 risk. However, R-RIC was associated with a significantly improved progression-free survival (RR = 0.76; 95%CI 0.62–0.92; p = 0.006. On subgroup analysis, mortality benefit was noted in the R-RIC group patients not receiving busulfan-based RIC (RR = 0.76; 95%CI = 0.60–0.96; p = 0.02 and with the use of a higher cumulative rituximab dose (RR = 0.43; 95%CI = 0.21–0.90; p = 0.02. Conclusion Our analysis shows that inclusion of rituximab in RIC regimens improves progression-free survival in patients with B cell NHL. These data supports the use of R-RIC in B

  5. Long-term trends and survival analysis of esophageal and gastric cancer in Yangzhong, 1991-2013.

    Directory of Open Access Journals (Sweden)

    Zhaolai Hua

    Full Text Available To describe the long-term trends of the incidence, mortality and survival of upper digestive tract cancers in a high-risk area of China.We extracted esophageal and gastric cancer cases diagnosed from 1991 to 2013 through the Yangzhong Cancer Registry and calculated the crude and age-standardized incidence and mortality rates. Cancer trends were calculated using the Joinpoint Regression Program and were reported using the annual percentage change (APC. The cancer-specific survival rates were evaluated and compared between groups using the Kaplan-Meier method and log-rank test.The age-standardized incidence rate of esophageal cancer declined from 107.06 per 100,000 person-years (male: 118.05 per 100,000 person-years; female: 97.42 per 100,000 person-years in 1991 to 37.04 per 100,000 person-years (male: 46.43 per 100,000 person-years; female: 27.26 per 100,000 person-years in 2013, with an APC of -2.5% (95% confidence interval (CI: -3.4%, -1.5% for males and -4.9% (95% CI:-5.8%, -3.9% for females. The age-standardized incidence rate of gastric cancer was 165.11 per 100,000 person-years (male: 225.39 per 100,000 person-years; female: 113.34 per 100,000 person-years in 1991 and 53.46 per 100,000 person-years (male: 76.51 per 100,000 person-years; female: 32.43 per 100,000 person-years in 2013, with the APC of -3.6% (95% CI: -4.5%, -2.7% for males and -4.8% (95% CI: -5.7%, -3.9% for females. The median survival time was 3.0 years for patients with esophageal or gastric cancer. Cancer cases detected after 2004 had a better prognosis.The age-standardized incidence rates of both esophageal and gastric cancer continuously decreased since 1991 through 2013, whereas the mortality rate remained stable before 2004 and significantly declined following the massive endoscopic screening program initiated in 2004. The survival probability of patients with esophageal and gastric cancer has improved obviously in recent decades.

  6. FBLN4 as candidate gene associated with long-term and short-term survival with primary glioblastoma

    Directory of Open Access Journals (Sweden)

    Li F

    2017-01-01

    Full Text Available Fubin Li,1,* Yiping Li,1,* Kewei Zhang,1,* Ye Li,1,* Ping He,1,* Yujia Liu,1,* Hongyan Yuan,2,* Honghua Lu,1,* Jinxiang Liu,1,* Songtian Che,3,* Zhenju Li,4,* Li Bie1,5 1Department of Neurosurgery of the First Clinical Hospital, 2Department of Immunology, Norman Bethune College of Medicine, 3Department of Neurosurgery of the Second Clinical Hospital, 4Department of Neurosurgery of the Fourth Clinical Hospital, Jilin University, Changchun, People’s Republic of China; 5Department of Pathology and Laboratory Medicine, School of Medicine, University of California – Irvine, Irvine, CA, USA *These authors contributed equally to this work Background: Glioblastoma multiforme (GBM is the most common malignant and lethal type of primary central nervous system tumor in humans. In spite of its high lethality, a small percentage of patients have a relatively good prognosis, with median survival times of 36 months or longer. The identification of clinical subsets of GBM associated with distinct molecular genetic profiles has made it possible to design therapies tailored to treat individual patients. Methods: We compared microarray data sets from long-term survivors (LTSs and short-term survivors (STSs to screen for prognostic biomarkers in GBM patients using the WebArrayDB platform. We focused on FBLN4, IGFBP-2, and CHI3L1, all members of a group of 10 of the most promising, differentially regulated gene candidates. Using formalin-fixed paraffin-embedded GBM samples, we corroborated the relationship between these genes and patient outcomes using methylation-specific polymerase chain reaction (PCR for MGMT methylation status and quantitative reverse transcription PCR for expression of these genes. Results: Expression levels of the mRNAs of these 3 genes were higher in the GBM samples than in normal brain samples and these 3 genes were significantly upregulated in STSs compared to the levels in LTS samples (P<0.01. Furthermore, Kaplan–Meier analysis

  7. ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma.

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    Hekun Jin

    Full Text Available BACKGROUND: Single nucleotide polymorphisms (SNPs in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC. MATERIALS AND METHODS: The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test. RESULTS: Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR 1.882; 95% confidence interval (CI 1.031-3.438; P = 0.039] and heavy smokers (≥20 pack-years carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010-4.036; P = 0.047 had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073-24.021; P = 0.002 or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056-6.248; P = 0.038. CONCLUSIONS: The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.

  8. Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study

    Directory of Open Access Journals (Sweden)

    Chen XR

    2016-09-01

    Full Text Available Xin-Ru Chen,1,* Jian-Zhong Liang,2,* Shu-Xiang Ma,1 Wen-Feng Fang,1 Ning-Ning Zhou,1 Hai Liao,1 De-Lan Li,1 Li-Kun Chen1 1Department of Medical Oncology, 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Concurrent chemoradiotherapy (CCRT is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC. However, the efficacy of consolidation chemotherapy (CCT in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods: This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC. Overall survival (OS and progression-free survival (PFS were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results: Among the 177 patients, 72 (41% received CCT and 105 (59% did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031, whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118. The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035, having undergone prophylactic cranial irradiation (P<0.001, and having received CCT (P=0.002 could serve as favorable independent prognostic factors

  9. Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.

    Science.gov (United States)

    Pailler, Emma; Oulhen, Marianne; Borget, Isabelle; Remon, Jordi; Ross, Kirsty; Auger, Nathalie; Billiot, Fanny; Ngo Camus, Maud; Commo, Frédéric; Lindsay, Colin R; Planchard, David; Soria, Jean-Charles; Besse, Benjamin; Farace, Françoise

    2017-05-01

    The duration and magnitude of clinical response are unpredictable in ALK -rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK -FISH patterns [ ALK -rearrangement, ALK -copy number gain ( ALK -CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK -rearranged patients. Thirty-nine ALK -rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively. Blood samples were collected at baseline and at an early time-point (2 months) on crizotinib. Aberrant ALK -FISH patterns were examined in CTCs using immunofluorescence staining combined with filter-adapted FISH after filtration enrichment. CTCs were classified into distinct subsets according to the presence of ALK -rearrangement and/or ALK -CNG signals. No significant association between baseline numbers of ALK -rearranged or ALK -CNG CTCs and PFS was observed. However, we observed a significant association between the decrease in CTC number with ALK -CNG on crizotinib and a longer PFS (likelihood ratio test, P = 0.025). In multivariate analysis, the dynamic change of CTC with ALK -CNG was the strongest factor associated with PFS (HR, 4.485; 95% confidence interval, 1.543-13.030, P = 0.006). Although not dominant, ALK -CNG has been reported to be one of the mechanisms of acquired resistance to crizotinib in tumor biopsies. Our results suggest that the dynamic change in the numbers of CTCs with ALK -CNG may be a predictive biomarker for crizotinib efficacy in ALK -rearranged NSCLC patients. Serial molecular analysis of CTC shows promise for real-time patient monitoring and clinical outcome prediction in this population. Cancer Res; 77(9); 2222-30. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

    Science.gov (United States)

    Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

    2016-09-01

    To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

  11. Effect of perioperative blood transfusion on the long-term survival of patients undergoing esophagectomy for esophageal cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Boshier, P R; Ziff, C; Adam, M E; Fehervari, M; Markar, S R; Hanna, G B

    2017-12-18

    Perioperative blood transfusion has been linked to poorer long-term survival in patients undergoing esophagectomy, presumably due to its potential immunomodulatory effects. This review aims to summarize existing evidence relating to the influence of blood transfusion on long-term survival following esophagectomy for esophageal cancer. A systematic literature search (up to February 2017) was conducted for studies reporting the effects of perioperative blood transfusion on survival following esophagectomy for esophageal cancer. Meta-analysis was used to summate survival outcomes. Twenty observational studies met the criteria for inclusion. Eighteen of these studies compared the outcomes of patients who received allogenic blood transfusion to patients who did not receive this intervention. Meta-analysis of outcomes revealed that allogenic blood transfusion significantly reduced long-term survival (HR = 1.49; 95% CI 1.26 to 1.76; P blood having lower long-term survival compared to patient who received between 0 and 2 units (HR = 1.59; 95% CI 1.31 to 1.93; P blood transfusion showed superior survival in the latter group. Factors associated with the requirement for perioperative blood transfusion included: intraoperative blood loss; preoperative hemoglobin; operative approach; operative time, and; presences of advanced disease. These findings indicate that perioperative blood transfusion is associated with significantly worse long-term survival in patients undergoing esophagectomy for esophageal cancer. Autologous donation of blood, meticulous intraoperative hemostasis, and avoidance of unnecessary transfusions may prevent additional deaths attributed to this intervention. © The Author(s) 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. A retrospective analysis of the results of p(65) + Be neutron therapy for the treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part I: survival and progression-free survival

    International Nuclear Information System (INIS)

    Scalliet, P.G.M.; Remouchamps, V.; Wambersie, A.; Richard, F.; Lhoas, F.; Van Glabbeke, M.; Curran, D.; Van Cangh, P.; Ledent, T.

    2001-01-01

    Purpose. -To retrospectively evaluate survival, progression free survival (PFS) and biological response in a series of patients irradiated with mixed neutron/photon beams for locally advanced prostate cancer in our institution. Patients and methods. - Three hundred and eight patients were treated between January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1 tumors after radical prostatectomy. Neo-adjuvant androgen deprivation was given in 106 patients. The treatment protocol consisted of a mixed photon/neutron irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA determinations were available in practically all cases. Study endpoints were overall survival (OAS) and progression-free survival (PFS). The Cox proportional hazard regression model was used to investigate the prognostic value of baseline characteristics on survival and progression-free survival were a progression was defined as local, regional, metastatic or biological progression. Mean age was 69 years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5-160) in those receiving neo-adjuvant hormonotherapy; seven patients only had an initial PSA S 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4% were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38% and III in 14% (5% unspecified). Results. -The median follow-up was 2.8 years (0-7.8). Five year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year progression-free survival (PFS) was 64% (95% Cl: 54-74%) for the entire series. PFS in patients with an initial PSA >- 20 ng/mL was the same. PFS could be predicted by two optimal Cox regression models, one including histological grade (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic factors for overall survival were PSA and age

  13. Pre-treatment hemodynamic features involved with long-term survival of cirrhotic patients after embolization of gastric fundal varices

    International Nuclear Information System (INIS)

    Maruyama, Hitoshi; Okugawa, Hidehiro; Kobayashi, Satoshi; Yoshizumi, Hiroaki; Yokosuka, Osamu

    2010-01-01

    Purpose: To clarify the pre-treatment hemodynamic features involved in the long-term survival of cirrhotic patients with gastric fundal varices (FV) after balloon-occluded retrograde transvenous obliteration (B-RTO). Materials and methods: Eighty-one cirrhotic patients with medium- or large-grade FV treated by B-RTO were enrolled in this retrospective study. Pre-treatment flow volume ratio between gastric vein and portal trunk (GP-R) was obtained by Doppler ultrasound. Results: The cumulative survival rate was 90% at 1 year, 74.8% at 3 years, 57.2% at 5 years, and 45.8% at 7 years without recurrence in a median period of 1148.5 days The survival was poorer in patients with HCC (47% at 3 years, 9.4% at 5 years, p < 0.0001) than without (89.2% at 3 years, 81.9% at 5 years, 67.5% at 7 years), in patients with Child B/C (57.7% at 3 years, 42.1% at 5 years, 28.1% at 7 years, p = 0.0016) than with Child A (91.8% at 3 years, 71.5% at 5 years, 62.1% at 7 years), and in patients with GP-R ≥ 1.0 (58.9% at 3 years, p = 0.0485) than with GP-R < 1.0 (76.3% at 3 years, 62% at 5 years, 49.6% at 7 years). Multivariate analysis identified the presence of HCC (hazard ratio, 12.486; 95% CI, 4.08-38.216; p < 0.0001), Child B/C (hazard ratio, 3.41; 95% CI, 1.594-7.15; p = 0.0051) and GP-R ≥ 1.0 (hazard ratio, 2.701; 95% CI, 1.07-6.15; p = 0.0221) as independent factors for poor prognosis. Conclusion: GP-R ≥ 1.0 on Doppler ultrasound before B-RTO may be a predictive indicator for poor prognosis in cirrhotic patients with FV after B-RTO, in addition to the presence of HCC and severe liver damage.

  14. Pre-treatment hemodynamic features involved with long-term survival of cirrhotic patients after embolization of gastric fundal varices

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Hitoshi, E-mail: maru-cib@umin.ac.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Okugawa, Hidehiro, E-mail: hideun@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Kobayashi, Satoshi, E-mail: kobakobakopa@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Yoshizumi, Hiroaki, E-mail: yossih04@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Yokosuka, Osamu, E-mail: yokosukao@faculty.chiba-u.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan)

    2010-08-15

    Purpose: To clarify the pre-treatment hemodynamic features involved in the long-term survival of cirrhotic patients with gastric fundal varices (FV) after balloon-occluded retrograde transvenous obliteration (B-RTO). Materials and methods: Eighty-one cirrhotic patients with medium- or large-grade FV treated by B-RTO were enrolled in this retrospective study. Pre-treatment flow volume ratio between gastric vein and portal trunk (GP-R) was obtained by Doppler ultrasound. Results: The cumulative survival rate was 90% at 1 year, 74.8% at 3 years, 57.2% at 5 years, and 45.8% at 7 years without recurrence in a median period of 1148.5 days The survival was poorer in patients with HCC (47% at 3 years, 9.4% at 5 years, p < 0.0001) than without (89.2% at 3 years, 81.9% at 5 years, 67.5% at 7 years), in patients with Child B/C (57.7% at 3 years, 42.1% at 5 years, 28.1% at 7 years, p = 0.0016) than with Child A (91.8% at 3 years, 71.5% at 5 years, 62.1% at 7 years), and in patients with GP-R {>=} 1.0 (58.9% at 3 years, p = 0.0485) than with GP-R < 1.0 (76.3% at 3 years, 62% at 5 years, 49.6% at 7 years). Multivariate analysis identified the presence of HCC (hazard ratio, 12.486; 95% CI, 4.08-38.216; p < 0.0001), Child B/C (hazard ratio, 3.41; 95% CI, 1.594-7.15; p = 0.0051) and GP-R {>=} 1.0 (hazard ratio, 2.701; 95% CI, 1.07-6.15; p = 0.0221) as independent factors for poor prognosis. Conclusion: GP-R {>=} 1.0 on Doppler ultrasound before B-RTO may be a predictive indicator for poor prognosis in cirrhotic patients with FV after B-RTO, in addition to the presence of HCC and severe liver damage.

  15. Similar long-term survival of consecutive in-hospital and out-of-hospital cardiac arrest patients treated with targeted temperature management

    DEFF Research Database (Denmark)

    Engsig, Magaly; Søholm, Helle; Folke, Fredrik

    2016-01-01

    OBJECTIVE: The long-term survival of in-hospital cardiac arrest (IHCA) patients treated with targeted temperature management (TTM) is poorly described. The aim of this study was to compare the outcomes of consecutive IHCA with out-of-hospital cardiac arrest (OHCA) patients treated with TTM. DESIGN...... SETTING AND PATIENTS: Retrospectively collected data on all consecutive adult patients treated with TTM at a university tertiary heart center between 2005 and 2011 were analyzed. MEASUREMENTS: Primary endpoints were survival to hospital discharge and long-term survival. Secondary endpoint was neurological...... time to return of spontaneous circulation (ROSC). Survival to hospital discharge was 54% for OHCA and 53% for IHCA (adjusted odds ratio 0.98 [95% confidence interval {CI}; 0.43-2.24]). Age ≤60 years, bystander CPR, time to ROSC ≤10 min, and shockable rhythm at presentation were associated with survival...

  16. Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

    Science.gov (United States)

    Mori, Keiichiro; Kimura, Takahiro; Onuma, Hajime; Kimura, Shoji; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Miki, Kenta; Egawa, Shin

    2017-07-01

    An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model. Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05). The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS. © 2017 Wiley Periodicals, Inc.

  17. Evaluating Expected Costs and Benefits of Granting Access to New Treatments on the Basis of Progression-Free Survival in Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Lakdawalla, Darius N; Chou, Jacquelyn W; Linthicum, Mark T; MacEwan, Joanna P; Zhang, Jie; Goldman, Dana P

    2015-05-01

    Surrogate end points may be used as proxy for more robust clinical end points. One prominent example is the use of progression-free survival (PFS) as a surrogate for overall survival (OS) in trials for oncologic treatments. Decisions based on surrogate end points may expedite regulatory approval but may not accurately reflect drug efficacy. Payers and clinicians must balance the potential benefits of earlier treatment access based on surrogate end points against the risks of clinical uncertainty. To present a framework for evaluating the expected net benefit or cost of providing early access to new treatments on the basis of evidence of PFS benefits before OS results are available, using non-small-cell lung cancer (NSCLC) as an example. A probabilistic decision model was used to estimate expected incremental social value of the decision to grant access to a new treatment on the basis of PFS evidence. The model analyzed a hypothetical population of patients with NSCLC who could be treated during the period between PFS and OS evidence publication. Estimates for delay in publication of OS evidence following publication of PFS evidence, expected OS benefit given PFS benefit, incremental cost of new treatment, and other parameters were drawn from the literature on treatment of NSCLC. Incremental social value of early access for each additional patient per month (in 2014 US dollars). For "medium-value" model parameters, early reimbursement of drugs with any PFS benefit yields an incremental social cost of more than $170,000 per newly treated patient per month. In contrast, granting early access on the basis of PFS benefit between 1 and 3.5 months produces more than $73,000 in incremental social value. Across the full range of model parameter values, granting access for drugs with PFS benefit between 3 and 3.5 months is robustly beneficial, generating incremental social value ranging from $38,000 to more than $1 million per newly treated patient per month, whereas access

  18. Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

    Science.gov (United States)

    Rathkopf, Dana E; Beer, Tomasz M; Loriot, Yohann; Higano, Celestia S; Armstrong, Andrew J; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Parli, Teresa; Bhattacharya, Suman; Phung, De; Krivoshik, Andrew; Scher, Howard I; Morris, Michael J

    2018-05-01

    Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients. To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS. PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016. Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment. Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula. In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0

  19. Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Ruella, Marco [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia (United States); Filippi, Andrea Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Bruna, Riccardo [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Di Russo, Anna [Radiation Oncology, Istituto Nazionale Tumori, Milano (Italy); Magni, Michele [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Caracciolo, Daniele [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Passera, Roberto [Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Matteucci, Paola; Di Nicola, Massimo [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Corradini, Paolo [Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Parvis, Guido [Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino (Italy); Gini, Guido; Olivieri, Attilio [Division of Haematology, Ospedali Riuniti, Ancona (Italy); Ladetto, Marco [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Tarella, Corrado, E-mail: corrado.tarella@gmail.com [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Hemato-Oncology Division, European Institute of Oncology, Milano (Italy); Devizzi, Liliana [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy)

    2016-03-15

    Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m{sup 2}, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

  20. Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

    International Nuclear Information System (INIS)

    Ruella, Marco; Filippi, Andrea Riccardo; Bruna, Riccardo; Di Russo, Anna; Magni, Michele; Caracciolo, Daniele; Passera, Roberto; Matteucci, Paola; Di Nicola, Massimo; Corradini, Paolo; Parvis, Guido; Gini, Guido; Olivieri, Attilio; Ladetto, Marco; Ricardi, Umberto; Tarella, Corrado; Devizzi, Liliana

    2016-01-01

    Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m"2, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

  1. Prognostic discrimination based on the EUTOS long-term survival score within the International Registry for Chronic Myeloid Leukemia in children and adolescents

    DEFF Research Database (Denmark)

    Millot, Frédéric; Guilhot, Joëlle; Suttorp, Meinolf

    2017-01-01

    The EUTOS Long-Term Survival score was tested in 350 children with chronic myeloid leukemia in first chronic phase treated with imatinib and registered in the International Registry for Childhood Chronic Myeloid Leukemia. With a median follow up of 3 years (range, 1 month to 6 years) progression ...

  2. A very rare case report of long-term survival: A patient operated on in 1994 of glioblastoma multiforme and currently in perfect health

    Directory of Open Access Journals (Sweden)

    Riccardo Caruso

    2017-01-01

    Conclusion: The fact that there are extremely rare cases of long-term survival and even zero recurrence of the glioblastoma should serve as a stimulus to continue the research effort and not give up the fight against this tumor on a day-to-day basis.

  3. Impact of aspirin and statins on long-term survival in patients hospitalized with acute myocardial infarction complicated by heart failure

    DEFF Research Database (Denmark)

    Lewinter, Christian; Bland, John M; Crouch, Simon

    2014-01-01

    AIMS: Aspirin and statins are established therapies for acute myocardial infarction (MI), but their benefits in patients with chronic heart failure (HF) remain elusive. We investigated the impact of aspirin and statins on long-term survival in patients hospitalized with acute MI complicated by HF...

  4. Prognostic discrimination based on the EUTOS long-term survival score within the International Registry for Chronic Myeloid Leukemia in children and adolescents

    NARCIS (Netherlands)

    Millot, Frederic; Guilhot, Joelle; Suttorp, Meinolf; Gunes, Adalet Meral; Sedlacek, Petr; De Bont, Eveline; Li, Chi Kong; Kalwak, Krzysztof; Lausen, Birgitte; Culic, Srdjana; Dworzak, Michael; Kaiserova, Emilia; De Moerloose, Barbara; Roula, Farah; Biondi, Andrea; Baruchel, Andre

    2017-01-01

    The EUTOS Long-Term Survival score was tested in 350 children with chronic myeloid leukemia in first chronic phase treated with imatinib and registered in the International Registry for Childhood Chronic Myeloid Leukemia. With a median follow up of 3 years (range, 1 month to 6 years) progression

  5. Inflammation-regulating factors in ascites as predictive biomarkers of drug resistance and progression-free survival in serous epithelial ovarian cancers

    International Nuclear Information System (INIS)

    Lane, Denis; Matte, Isabelle; Garde-Granger, Perrine; Laplante, Claude; Carignan, Alex; Rancourt, Claudine; Piché, Alain

    2015-01-01

    Platinum-based combination therapy is the standard first-line treatment for women with advanced serous epithelial ovarian carcinoma (EOC). However, about 20 % will not respond and are considered clinically resistant. The availability of biomarkers to predict responses to the initial therapy would provide a practical approach to identify women who would benefit from a more appropriate first-line treatment. Ascites is an attractive inflammatory fluid for biomarker discovery as it is easy and minimally invasive to obtain. The aim of this study was to evaluate whether six selected inflammation-regulating factors in ascites could serve as diagnostic or drug resistance biomarkers in patients with advanced serous EOC. A total of 53 women with stage III/IV serous EOC and 10 women with benign conditions were enrolled in this study. Eleven of the 53 women with serous EOC were considered clinically resistant to treatment with progression-free survival < 6 months. Ascites were collected at the time of the debulking surgery and the levels of cytokines were measured by ELISA. The six selected cytokines were evaluated for their ability to discriminate serous EOC from benign controls, and to discriminate platinum resistant from platinum sensitive patients. Median ascites levels of IL-6, IL-10 and osteoprotegerin (OPG) were significantly higher in women with advanced serous EOC than in controls (P ≤ 0.012). There were no significant difference in the median ascites levels of leptin, soluble urokinase plasminogen activator receptor (suPAR) and CCL18 among serous EOC women and controls. In Receiver Operator curve (ROC) analysis, IL-6, IL-10 and OPG had a high area under the curve value of 0.905, 0.832 and 0.825 respectively for distinguishing EOC from benign controls. ROC analysis of individual cytokines revealed low discriminating potential to stratify patients according to their sensitivity to first-line treatment. The combination of biomarkers with the highest discriminating

  6. Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    Furlong, Fiona

    2012-04-01

    Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3\\' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3\\'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3\\' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

  7. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

  8. Long-Term Survival Prediction for Coronary Artery Bypass Grafting: Validation of the ASCERT Model Compared With The Society of Thoracic Surgeons Predicted Risk of Mortality.

    Science.gov (United States)

    Lancaster, Timothy S; Schill, Matthew R; Greenberg, Jason W; Ruaengsri, Chawannuch; Schuessler, Richard B; Lawton, Jennifer S; Maniar, Hersh S; Pasque, Michael K; Moon, Marc R; Damiano, Ralph J; Melby, Spencer J

    2018-05-01

    The recently developed American College of Cardiology Foundation-Society of Thoracic Surgeons (STS) Collaboration on the Comparative Effectiveness of Revascularization Strategy (ASCERT) Long-Term Survival Probability Calculator is a valuable addition to existing short-term risk-prediction tools for cardiac surgical procedures but has yet to be externally validated. Institutional data of 654 patients aged 65 years or older undergoing isolated coronary artery bypass grafting between 2005 and 2010 were reviewed. Predicted survival probabilities were calculated using the ASCERT model. Survival data were collected using the Social Security Death Index and institutional medical records. Model calibration and discrimination were assessed for the overall sample and for risk-stratified subgroups based on (1) ASCERT 7-year survival probability and (2) the predicted risk of mortality (PROM) from the STS Short-Term Risk Calculator. Logistic regression analysis was performed to evaluate additional perioperative variables contributing to death. Overall survival was 92.1% (569 of 597) at 1 year and 50.5% (164 of 325) at 7 years. Calibration assessment found no significant differences between predicted and actual survival curves for the overall sample or for the risk-stratified subgroups, whether stratified by predicted 7-year survival or by PROM. Discriminative performance was comparable between the ASCERT and PROM models for 7-year survival prediction (p validated for prediction of long-term survival after coronary artery bypass grafting in all risk groups. The widely used STS PROM performed comparably as a predictor of long-term survival. Both tools provide important information for preoperative decision making and patient counseling about potential outcomes after coronary artery bypass grafting. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Survival analysis of increases in care needs associated with dementia and living alone among older long-term care service users in Japan.

    Science.gov (United States)

    Lin, Huei-Ru; Otsubo, Tetsuya; Imanaka, Yuichi

    2017-08-15

    Japan is known for its long life expectancy and rapidly aging society that there are various demands of older adults need to be fulfilled with, and one of them is long-term care needs. Therefore, Japan implemented the Long-Term Care Insurance in year 2000 for citizens who are above 65-year old and citizens who are above 40-year old in needs of long-term care services. This study was undertaken to longitudinally examine the influence of dementia and living alone on care needs increases among older long-term care insurance service users in Japan. Long-term care insurance claims data were used to identify enrollees who applied for long-term care services between October 2010 and September 2011, and subjects were tracked until March 2015. A Kaplan-Meier survival analysis was conducted to examine increases in care needs over time in months. Cox regression models were used to examine the effects of dementia and living alone on care needs increases. The cumulative survival rates before care needs increased over the 4.5-year observation period were 17.6% in the dementia group and 31.9% in the non-dementia group. After adjusting for age, sex, care needs level, and status of living alone, the risk of care needs increases was found to be 1.5 times higher in the dementia group. Living alone was not a significant risk factor of care needs increases, but people with dementia who lived alone had a higher risk of care needs increases than those without dementia. Dementia, older age, the female sex, and lower care needs levels were associated with a higher risk of care needs increases over the study period. Among these variables, dementia had the strongest impact on care needs increases, especially in persons who lived alone.

  10. Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory.

    Directory of Open Access Journals (Sweden)

    Florence Kermen

    Full Text Available BACKGROUND: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days, but not a massed (within day, learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. CONCLUSION/SIGNIFICANCE: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory.

  11. Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory.

    Science.gov (United States)

    Kermen, Florence; Sultan, Sébastien; Sacquet, Joëlle; Mandairon, Nathalie; Didier, Anne

    2010-08-13

    It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days), but not a massed (within day), learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory.

  12. Short and long-term survival after primary percutaneous coronary intervention in young patients with ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Waziri, Homa; Jørgensen, Erik; Kelbæk, Henning

    2016-01-01

    UNLABELLED: The long-term prognosis of patients with ST-elevation myocardial infarction (STEMI) aged 45 years or younger and differences according to gender have not been well characterized. METHODS: We included 16,685 consecutive STEMI patients from 2003 to 2012 (67,992 patient-years follow-up) ...

  13. Long-term Survival of Straumann Dental Implants with TPS Surfaces: A Retrospective Study with a Follow-up of 12 to 23 Years.

    Science.gov (United States)

    Becker, Stephan T; Beck-Broichsitter, Benedicta E; Rossmann, Christian M; Behrens, Eleonore; Jochens, Arne; Wiltfang, Jörg

    2016-06-01

    The aim of this study was to evaluate the long-term dental implant survival rates of Straumann dental implants in a university hospital environment over 12 to 23 years. A total of 388 Straumann dental implants with titanium-sprayed surfaces (TPS) were inserted in 92 patients between 1988 and 1999 in the Department of Oral and Maxillofacial Surgery of the University Hospital Schleswig-Holstein in Kiel, and they were reevaluated with standardized clinical and radiological exams. Kaplan-Meier analyses were performed for individual factors. Cox proportional hazard regression analysis was used to detect the factors influencing long-term implant failure. The long-term implant survival rate was 88.03% after an observation time of 12.2 to 23.5 years. Cox regression revealed statistically significant influences of the International Team for Implantology (ITI) implantation type (p = .00354) and tobacco smoking (p = .01264) on implant failure. A proportion 82.8% of the patients with implant losses had a medical history of periodontitis. Peri-implantitis was diagnosed in 9.7% of the remaining implants in the long-term survey. This study emphasized the long-term rehabilitation capabilities of Straumann dental implants in complex cases. The survival rates after several years constitute important information for patients, as well as for clinicians, in deciding about different concepts of tooth replacement. Patient-related and technical factors - determined before implant placement - could help to predict the risk of implant loss. © 2015 Wiley Periodicals, Inc.

  14. [Comparison liver resection with transarterial chemoembolization for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma patients on long-term survival after SPSS propensity score matching].

    Science.gov (United States)

    Ke, Yang; Zhong, Jianhong; Guo, Zhe; Liang, Yongrong; Li, Lequn; Xiang, Bangde

    2014-03-18

    To compare the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) undergoing either liver resection or transarterial chemoembolization (TACE) after propensity score matching (PSM). One hundred sixty-seven and 70 BCLC-B HCC patients undergoing liver resection and TACE were retrospectively collected. PSM function of SPSS software was conducted to reduce confounding bias between the groups. And then survival analysis was performed for the matched data. Fifty-three pairs of patients were successfully matched. And then survival analysis showed that the median survival periods and their 95% confidence intervals were 35.0 (26.3-43.7)months in the liver resection group versus 20.0(15.0-25.0) months in the TACE group. The 1, 3, 5 and 7-year survival rates were 91.0%, 49.0%, 30.0% and 17.0% in the liver resection group versus 73.0%, 25.0%, 8.0% and 5.0% respectively in the TACE group (P = 0.001). Cox regression analysis revealed that TACE, total bilirubin ≥ 34.2 µmol/L, alpha fetoprotein ≥ 400 ng/ml and tumor number ≥ 3 were independent risk factors of survival (hazard ratio >1, P < 0.05). The balance of covariates may be achieved through PSM. And for patients with BCLC-B HCC, liver resection provides better long-term overall survival than TACE.

  15. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer

    DEFF Research Database (Denmark)

    Maase, Hans von der; Sengeløv, Lisa; Roberts, James T.

    2005-01-01

    PURPOSE: To compare long-term survival in patients with locally advanced       or metastatic transitional cell carcinoma (TCC) of the urothelium treated       with gemcitabine/cisplatin (GC) or       methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND       METHODS: Efficacy data...... in patients with locally advanced or       metastatic TCC...

  16. How the definition of acceptable antigens and epitope analysis can facilitate transplantation of highly sensitized patients with excellent long-term graft survival.

    Science.gov (United States)

    Heidt, Sebastiaan; Haasnoot, Geert W; Claas, Frans H J

    2018-05-24

    Highly sensitized patients awaiting a renal transplant have a low chance of receiving an organ offer. Defining acceptable antigens and using this information for allocation purposes can vastly enhance transplantation of this subgroup of patients, which is the essence of the Eurotransplant Acceptable Mismatch program. Acceptable antigens can be determined by extensive laboratory testing, as well as on basis of human leukocyte antigen (HLA) epitope analyses. Within the Acceptable Mismatch program, there is no effect of HLA mismatches on long-term graft survival. Furthermore, patients transplanted through the Acceptable Mismatch program have similar long-term graft survival to nonsensitized patients transplanted through regular allocation. Although HLA epitope analysis is already being used for defining acceptable HLA antigens for highly sensitized patients in the Acceptable Mismatch program, increasing knowledge on HLA antibody - epitope interactions will pave the way toward the definition of acceptable epitopes for highly sensitized patients in the future. Allocation based on acceptable antigens can facilitate transplantation of highly sensitized patients with excellent long-term graft survival.

  17. Similar long-term survival of consecutive in-hospital and out-of-hospital cardiac arrest patients treated with targeted temperature management

    Directory of Open Access Journals (Sweden)

    Engsig M

    2016-11-01

    Full Text Available Magaly Engsig,1 Helle Søholm,2 Fredrik Folke,3,4 Peter J Gadegaard,1 Julie Therese Wiis,5 Rune Molin,6 Thomas Mohr,1 Frederik N Engsig7 1Department of Anaesthesiology and Intensive Care, Copenhagen University Hospital, Hellerup, 2Department of Cardiology, Copenhagen University Hospital, Herlev, 3Department of Cardiology, Copenhagen University Hospital, Hellerup, 4Pre-Hospital Emergency Medical Services, Capital Region of Denmark, Ballerup, 5Department of Intensive Care, Copenhagen University Hospital, Copenhagen, 6Department of Anaesthesiology, Copenhagen University Hospital, Hillerød, 7Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark Objective: The long-term survival of in-hospital cardiac arrest (IHCA patients treated with targeted temperature management (TTM is poorly described. The aim of this study was to compare the outcomes of consecutive IHCA with out-of-hospital cardiac arrest (OHCA patients treated with TTM. Design, setting, and patients: Retrospectively collected data on all consecutive adult patients treated with TTM at a university tertiary heart center between 2005 and 2011 were analyzed. Measurements: Primary endpoints were survival to hospital discharge and long-term survival. Secondary endpoint was neurological outcome assessed using the Pittsburgh cerebral performance category (CPC. Results: A total of 282 patients were included in this study; 233 (83% OHCA and 49 (17% IHCA. The IHCA group presented more often with asystole, received bystander cardiopulmonary resuscitation (CPR in all cases, and had shorter time to return of spontaneous circulation (ROSC. Survival to hospital discharge was 54% for OHCA and 53% for IHCA (adjusted odds ratio 0.98 [95% confidence interval {CI}; 0.43–2.24]. Age ≤60 years, bystander CPR, time to ROSC ≤10 min, and shockable rhythm at presentation were associated with survival to hospital discharge. Good neurologic outcome among survivors was achieved by 86

  18. Impact of donor-recipient sex match on long-term survival after heart transplantation in children: An analysis of 5797 pediatric heart transplants.

    Science.gov (United States)

    Kemna, Mariska; Albers, Erin; Bradford, Miranda C; Law, Sabrina; Permut, Lester; McMullan, D Mike; Law, Yuk

    2016-03-01

    The effect of donor-recipient sex matching on long-term survival in pediatric heart transplantation is not well known. Adult data have shown worse survival when male recipients receive a sex-mismatched heart, with conflicting results in female recipients. We analyzed 5795 heart transplant recipients ≤ 18 yr in the Scientific Registry of Transplant Recipients (1990-2012). Recipients were stratified based on donor and recipient sex, creating four groups: MM (N = 1888), FM (N = 1384), FF (N = 1082), and MF (N = 1441). Males receiving sex-matched donor hearts had increased unadjusted allograft survival at five yr (73.2 vs. 71%, p = 0.01). However, this survival advantage disappeared with longer follow-up and when adjusted for additional risk factors by multivariable Cox regression analysis. In contrast, for females, receiving a sex-mismatched heart was associated with an 18% higher risk of allograft loss over time compared to receiving a sex-matched heart (HR 1.18, 95% CI: 1.00-1.38) and a 26% higher risk compared to sex-matched male recipients (HR 1.26, 95% CI: 1.10-1.45). Females who receive a heart from a male donor appear to have a distinct long-term survival disadvantage compared to all other groups. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation: long-term results from the Bio-CAPTURE registry.

    Science.gov (United States)

    van den Reek, J M P A; Tummers, M; Zweegers, J; Seyger, M M B; van Lümig, P P M; Driessen, R J B; van de Kerkhof, P C M; Kievit, W; de Jong, E M G J

    2015-03-01

    Drug survival is an indicator for treatment success; insight in predictors associated with drug survival is important. To analyse the long-term drug survival for adalimumab in patients with psoriasis treated in daily practice and (II) to identify predictors of prolonged drug survival for adalimumab split for different reasons of discontinuation. Data were extracted from a prospective psoriasis cohort and analysed using Kaplan-Meier survival curves split for reasons of discontinuation. Baseline predictors associated with longer drug survival were identified using multivariate Cox-regression analysis. One hundred and sixteen patients were included with a total of 208 patient-years. Overall drug survival was 76% after 1 year and 52% after 4.5 years. In patients who stopped due to ineffectiveness, longer drug survival was associated with the absence of specific comorbidities (P = 0.03). In patients who stopped due to side-effects, longer drug survival was associated with male gender (P = 0.02). Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation. Strong, specific predictors can lead to patient-tailored treatment. © 2014 European Academy of Dermatology and Venereology.

  20. Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

    Science.gov (United States)

    Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

    2015-12-22

    Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

  1. Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database.

    Science.gov (United States)

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T; Adams, Richard; Saltz, Leonard; Goldberg, Richard M; Punt, Cornelis J A; Douillard, Jean-Yves; Hoff, Paulo M; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J

    2015-01-01

    Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. © 2014 by American Society of Clinical Oncology.

  2. Long-term survival in patients hospitalized for chronic obstructive pulmonary disease: a prospective observational study in the Nordic countries

    Directory of Open Access Journals (Sweden)

    Gudmundsson G

    2012-09-01

    Full Text Available Gunnar Gudmundsson,1,2 Charlotte Suppli Ulrik,3 Thorarinn Gislason,1,2 Eva Lindberg,4 Eva Brøndum,3 Per Bakke,5 Christer Janson31Department of Respiratory Medicine, Allergy and Sleep, National University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Respiratory Diseases, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; 4Department of Medical Sciences: Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden; 5Haukeland University Hospital, Bergen, NorwayBackground and aim: Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD. Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.Methods: A total of 256 patients from the Nordic countries were followed for 8.7 ± 0.4 years after the index hospitalization in 2000–2001. Prior to discharge, the St George’s Respiratory Questionnaire was administered and data on therapy and comorbidities were obtained. Information on long-term mortality was obtained from national registries in each of the Nordic countries.Results: In total, 202 patients (79% died during the follow up period, whereas 54 (21% were still alive. Primary cause of death was respiratory (n = 116, cardiovascular (n = 43, malignancy (n = 28, other (n = 10, or unknown (n = 5. Mortality was related to older age, with a hazard risk ratio (HRR of 1.75 per 10 years, lower forced expiratory volume in 1 second (FEV1 (HRR 0.80, body mass index (BMI <20 kg/m2 (HRR 3.21, and diabetes (HRR 3.02. Older age, lower BMI, and diabetes were related to both respiratory and cardiovascular mortality. An association was also found between lower FEV1 and respiratory mortality, whereas mortality was not significantly associated with therapy, anxiety, or depression.Conclusion: Almost four out of five patients died within 9 years following an admission

  3. Combination of survival probabilities of the components in a system. An application to long-term financial valuation

    Directory of Open Access Journals (Sweden)

    Salvador Cruz Rambaud

    2011-12-01

    Full Text Available The Net Present Value (NPV is a well-known method to value an investment project. Nevertheless, this methodology exhibits a serious problem when the used discounting function decreases very rapidly, especially in (very long-term projects, because the future cash-flows are not significant in the expression of the NPV. For this reason, this paper introduces a methodology to correct the discounting function used for valuing. To do this, a new operation between discounting functions is defined by reducing the (cumulative instantaneous discount rate corresponding of the valuing discounting function with another appropriate discounting function. The result is a new discounting function which can be more adequate to value this class of investment projects.

  4. Mechanical dyssynchrony evaluated by tissue Doppler cross-correlation analysis is associated with long-term survival in patients after cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Risum, Niels; Williams, Eric S; Khouri, Michel G

    2013-01-01

    Aims Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. Methods and results In 131 patients referred for cardiac resynchroniz......Aims Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. Methods and results In 131 patients referred for cardiac......-max was independently associated with improved survival when adjusted for QRS > 150 ms and aetiology {hazard ratio (HR) 0.35 [95% confidence interval (CI) 0.16-0.77], P = 0.01}. Maximal activation delay performed significantly better than Yu index, OWD, and the presence of left bundle branch block (P ..., for difference between parameters). In subgroup analysis, patients without dyssynchrony and QRS between 120 and 150 ms showed a particularly poor survival [HR 4.3 (95% CI 1.46-12.59), P

  5. The influence of cultural treatments of the long-term survival and growth of planted Quercus rubra

    Science.gov (United States)

    James J. Zaczek; Kim C. Steiner

    2011-01-01

    A northern red oak (Quercus rubra L.) plantation testing 20 nursery stock and planting methods was used to evaluate treatments 3, 6, 10, and 17 years after planting. Survival over all treatments was 92 percent at age 3 and declined to 74 percent, 56 percent, and 39 percent at ages 6, 10, and 17, respectively. At age 17, survival was highest for...

  6. Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.

    Science.gov (United States)

    Fukushima, N; Sakamoto, M; Mukai, K; Kanai, Y; Shimada, K; Kosuge, T; Hirohashi, S

    2001-08-01

    Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.

  7. Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.

    Science.gov (United States)

    Viganò, Luca; Capussotti, Lorenzo; De Rosa, Giovanni; De Saussure, Wassila Oulhaci; Mentha, Gilles; Rubbia-Brandt, Laura

    2013-11-01

    We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival

  8. Perioperative Outcomes and Long-term Survival in Clinically Early-stage Thymic 
Malignancies: Video-assisted Thoracoscopic Thymectomy versus Open Approaches

    Directory of Open Access Journals (Sweden)

    Hao WANG

    2016-07-01

    Full Text Available Background and objective Video-assisted thoracoscopic surgery (VATS theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II thymic malignancies. However, longterm outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART. Methods Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group, while 876 cases underwent open thymectomy (Open group. Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs 73.9%, P=0.028, resection rate (98.8% vs 88.7%, P<0.001 and less recurrence (2.9% vs 16.0%, P<0.001. Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15. However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011. Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. Conclusion This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival.

  9. Long-term functional and survival outcomes after induction chemotherapy and risk-based definitive therapy for locally advanced squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Hutcheson, Katherine A; Lewin, Jan S; Holsinger, F Christopher; Steinhaus, Ganene; Lisec, Asher; Barringer, Denise A; Lin, Heather Y; Villalobos, Sandra; Garden, Adam S; Papadimitrakopoulou, Vali; Kies, Merrill S

    2014-04-01

    The purpose of this study was to evaluate long-term outcomes after induction chemotherapy followed by "risk-based" local therapy for locally-advanced squamous cell carcinoma of the head and neck (SCCHN). Forty-seven patients (stage IV; ≥N2b) were enrolled in a phase II trial. Baseline and 24-month functional measures included modified barium swallow (MBS) studies, oropharyngeal swallow efficiency (OPSE), and the MD Anderson Dysphagia Inventory (MDADI). Functional status was assessed at 5 years. Five-year overall survival (OS) was 89% (95% confidence interval [CI], 81% to 99%). A nonsignificant 13% average reduction in swallowing efficiency (OPSE) was observed at 24 months relative to baseline (p = .191). MDADI scores approximated baseline at 24 months. Among 42 long-term survivors (median, 5.9 years), 3 patients (7.1%) had chronic dysphagia. The rate of final gastrostomy dependence was 4.8% (2 of 42). Sequential chemoradiotherapy achieved favorable outcomes among patients with locally advanced SCCHN, mainly of oropharyngeal origin. MBS and MDADI scores found modest swallowing deterioration at 2 years, and chronic aspiration was uncommon in long-term survivors. Copyright © 2013 Wiley Periodicals, Inc.

  10. Survival analysis, long-term outcomes, and percentage of recovery up to 8 years post-infection among the Houston West Nile virus cohort.

    Directory of Open Access Journals (Sweden)

    Kristy O Murray

    Full Text Available In 2012, we witnessed a resurgence of West Nile virus (WNV in the United States, with the largest outbreak of human cases reported since 2003. WNV is now endemic and will continue to produce epidemics over time, therefore defining the long-term consequences of WNV infection is critical. Over a period of eight years, we prospectively followed a cohort of 157 WNV-infected subjects in the Houston metropolitan area to observe recovery over time and define the long-term clinical outcomes. We used survival analysis techniques to determine percentage of recovery over time and the effects of demographic and co-morbid conditions on recovery. We found that 40% of study participants continued to experience symptoms related to their WNV infection up to 8 years later. Having a clinical presentation of encephalitis and being over age 50 were significantly associated with prolonged or poor recovery over time. Since the health and economic impact as a result of prolonged recovery, continued morbidity, and related disability is likely substantial in those infected with WNV, future research should be aimed at developing effective vaccines to prevent illness and novel therapeutics to minimize morbidity, mortality, and long-term complications from infection.

  11. Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores.

    Science.gov (United States)

    Lewin, Joel W; O'Rourke, Nicholas A; Chiow, Adrian K H; Bryant, Richard; Martin, Ian; Nathanson, Leslie K; Cavallucci, David J

    2016-02-01

    This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  12. Prognostic model for long-term survival of locally advanced non-small-cell lung cancer patients after neoadjuvant radiochemotherapy and resection integrating clinical and histopathologic factors

    International Nuclear Information System (INIS)

    Pöttgen, Christoph; Stuschke, Martin; Graupner, Britta; Theegarten, Dirk; Gauler, Thomas; Jendrossek, Verena; Freitag, Lutz; Jawad, Jehad Abu; Gkika, Eleni; Wohlschlaeger, Jeremias; Welter, Stefan; Hoiczyk, Matthias; Schuler, Martin; Stamatis, Georgios; Eberhardt, Wilfried

    2015-01-01

    Outcome of consecutive patients with locally advanced non-small cell lung cancer and histopathologically proven mediastional lymph node metastases treated with induction chemotherapy, neoadjuvant radiochemotherapy and thoracotomy at the West German Cancer Center between 08/2000 and 06/2012 was analysed. A clinico-pathological prognostic model for survival was built including partial or complete response according to computed tomography imaging (CT) as clinical parameters as well as pathologic complete remission (pCR) and mediastinal nodal clearance (MNC) as histopathologic factors. Proportional hazard analysis (PHA) and recursive partitioning analysis (RPA) were used to identify prognostic factors for survival. Long-term survival was defined as survival ≥ 36 months. A total of 157 patients were treated, median follow-up was 97 months. Among these patients, pCR and MNC were observed in 41 and 85 patients, respectively. Overall survival was 56 ± 4% and 36 ± 4% at 24 and 60 months, respectively. Sensitivities of pCR and MNC to detect long-term survivors were 38% and 61%, specificities were 84% and 52%, respectively. Multivariable survival analysis revealed pCR, cN3 category, and gender, as prognostic factors at a level of α < 0.05. Considering only preoperative available parameters, CT response became significant. Classifying patients with a predicted hazard above the median as high risk group and the remaining as low risk patients yielded better separation of the survival curves by the inclusion of histopathologic factors than by preoperative factors alone (p < 0.0001, log rank test). Using RPA, pCR was identified as the top prognostic factor above clinical factors (p = 0.0006). No long term survivors were observed in patients with cT3-4 cN3 tumors without pCR. pCR is the dominant histopathologic response parameter and improves prognostic classifiers, based on clinical parameters. The validated prognostic model can be used to estimate individual prognosis and

  13. Swan-neck versus straight peritoneal dialysis catheter: Long-term effect on patient and method survival.

    Science.gov (United States)

    Filiopoulos, V; Biblaki, D; Takouli, L; Dounavis, A; Hadjiyannakos, D; Vlassopoulos, D

    2016-09-01

    Peritoneal dialysis (PD) is limited mainly by a higher technique failure rate as compared to hemodialysis (HD), catheter malfunction being an important reason. Intra- and extra-peritoneal catheter configuration may be associated with mechanical and infectious complications affecting method survival. We report our experience with two extra-peritoneal catheter configurations: the straight and the swan-neck (SN) catheters. A total of 85 consecutive patients, 58 males and 27 females were included in the study. Among them, 26 were diabetics; 52 were treated with automated PD (APD) and 33 with continuous ambulatory PD (CAPD). Straight catheters were used in 38 patients (straight group) and SN catheters in 47 patients (SN group). Straight catheters were mostly used in the first 6-year period while SN catheters in the last 6-year period. The baseline demographics were similar between the two groups. A significantly higher frequency of APD use was observed in SN group. Technique survival was better with SN versus straight (log-rank test, P = 0.01) while patient and catheter survival were similar. A better technique survival is noted in our group of patients with SN catheters. An additional factor could be the significantly higher frequency of APD use in this group. Changes in PD solutions' composition could also contribute to improvement in technique survival. The outcome for patients and catheter types used was similar.

  14. Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol.

    Science.gov (United States)

    Sedlacek, Scot M; Playdon, Mary C; Wolfe, Pamela; McGinley, John N; Wisthoff, Mark R; Daeninck, Elizabeth A; Jiang, Weiqin; Zhu, Zongjian; Thompson, Henry J

    2011-07-06

    Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction. Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m²) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin. While clinical data indicate that excess weight for height is associated with poor prognosis for long term

  15. Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE': study protocol

    Directory of Open Access Journals (Sweden)

    Daeninck Elizabeth A

    2011-07-01

    Full Text Available Abstract Background Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction. Methods/Design Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m2 will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF, IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin. Discussion While clinical data indicate that excess weight

  16. Complex interplay between intrinsic and extrinsic drivers of long-term survival trends in southern elephant seals

    Directory of Open Access Journals (Sweden)

    McMahon Clive R

    2007-03-01

    Full Text Available Abstract Background Determining the relative contribution of intrinsic and extrinsic factors to fluctuations in population size, trends and demographic composition is analytically complex. It is often only possible to examine the combined effects of these factors through measurements made over long periods, spanning an array of population densities or levels of food availability. Using age-structured mark-recapture models and datasets spanning five decades (1950–1999, and two periods of differing relative population density, we estimated age-specific probabilities of survival and examined the combined effects of population density and environmental conditions on juvenile survival of southern elephant seals at Macquarie Island. Results First-year survival decreased with density during the period of highest population size, and survival increased during years when the Southern Oscillation Index (SOI anomaly (deviation from a 50-year mean during the mother's previous foraging trip to sea was positive (i.e., El Niño. However, when environmental stochasticity and density were considered together, the effect of density on first-year survival effectively disappeared. Ignoring density effects also leads to models placing too much emphasis on the environmental conditions prevailing during the naïve pup's first year at sea. Conclusion Our analyses revealed that both the state of the environment and population density combine to modify juvenile survival, but that the degree to which these processes contributed to the variation observed was interactive and complex. This underlines the importance of evaluating the relative contribution of both the intrinsic and extrinsic factors that regulate animal populations because false conclusions regarding the importance of population regulation may be reached if they are examined in isolation.

  17. Long-term disorders of memory in the persons survived acute radiation sickness due to Chernobyl accident

    International Nuclear Information System (INIS)

    Antipchuk, K.Yu.

    2003-01-01

    The study involved two groups of the patients: main group - 52 men survived ARS aged 35-55, controls - 23 healthy men aged 36-55. Auditory and visual memory was studied. The obtained results suggest that the changes in the structure of the anterior portions of the brain which are responsible for obtaining, processing and reproduction of verbal information, namely the cortex of the left temporal and frontal regions with their cortical-subcortical associations, play the leading role in the memory disorders in persons survived ARS

  18. Long-term survival after resection of a primary leiomyosarcoma of the innominate vein Report of a case.

    Science.gov (United States)

    Illuminati, Giulio; Miraldi, Fabio; A Pacilè, Maria; Palumbo, Piero; Vietri, Francesco

    2012-10-29

    Leiomyosarcoma of the innominate vein is a rare but usually lethal disease. We report the case of a 50-year-old woman, undergoing a curative resection of the tumor. She is alive and free of disease at 88-month follow-up. Surgical excision remains the current optimal treatment able to provide a chance of cure. KEY WORDS: Late survival, Venous leiomyosarcoma.

  19. Robust evidence for long-term survival with {sup 90}Y radioembolization in chemorefractory liver-predominant metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jakobs, T.F. [Barmherzige Brueder Munich, Department of Diagnostic and Interventional Radiology, Munich (Germany); Paprottka, K.J.; Raessler, F.; Strobl, F.; Trumm, C.G.; Sommer, W.; Paprottka, P.M. [LMU - University of Munich, Department of Clinical Radiology, Munich (Germany); Lehner, S.; Ilhan, H.; Fendler, W.P. [LMU - University of Munich, Department of Nuclear Medicine, Munich (Germany)

    2017-01-15

    Our aim was to provide further evidence for the efficacy/safety of radioembolization using yttrium-90-resin microspheres for unresectable chemorefractory liver metastases from colorectal cancer (mCRC). We followed 104 consecutively treated patients until death. Overall survival (OS) was calculated from the day of the first radioembolization procedure. Response was defined by changes in tumour volume as defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 and/or a ≥30 % reduction in serum carcinoembryonic antigen (CEA) at 3 months. Survival varied between 23 months in patients who had a complete response to prior chemotherapy and 13 months in patients with a partial response or stable disease. Median OS also significantly improved (from 5.8 months to 17.1 months) if response durability to radioembolization extended beyond 6 months. Patients with a positive trend in CEA serum levels (≥30 % reduction) at 3 months post-radioembolization also had a survival advantage compared with those who did not: 15.0 vs 6.7 months. Radioembolization was well tolerated. Grade 3 increases in bilirubin were reported in 5.0 % of patients at 3 months postprocedure. After multiple chemotherapies, many patients still have a good performance status and are eligible for radioembolization. This single procedure can achieve meaningful survivals and is generally well tolerated. (orig.)

  20. Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation.

    Science.gov (United States)

    Bitan, Menachem; Ahn, Kwang Woo; Millard, Heather R; Pulsipher, Michael A; Abdel-Azim, Hisham; Auletta, Jeffery J; Brown, Valerie; Chan, Ka Wah; Diaz, Miguel Angel; Dietz, Andrew; Vincent, Marta González; Guilcher, Gregory; Hale, Gregory A; Hayashi, Robert J; Keating, Amy; Mehta, Parinda; Myers, Kasiani; Page, Kristin; Prestidge, Tim; Shah, Nirali N; Smith, Angela R; Woolfrey, Ann; Thiel, Elizabeth; Davies, Stella M; Eapen, Mary

    2017-09-01

    We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML, n = 790) and acute lymphoblastic leukemia (ALL, n = 1096) who underwent transplantation between 2000 and 2010 and who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease-, and transplantation characteristics and acute and chronic graft-versus-host disease (GVHD) was performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. We did not identify any prognostic factors beyond 4 years after transplantation for AML and beyond 3 years for ALL. Risk score for survival for AML includes age, disease status at transplantation, cytogenetic risk group, and chronic GVHD. For ALL, the risk score includes age at transplantation and chronic GVHD. The 10-year probabilities of OS for AML with good (score 0, 1, or 2), intermediate (score 3), and poor risk (score 4, 5, 6, or 7) were 94%, 87%, and 68%, respectively. The 10-year probabilities of OS for ALL were 89% and 80% for good (score 0 or 1) and poor risk (score 2), respectively. Identifying children at risk for late mortality with early intervention may mitigate some excess late mortality. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Long-term survival rate of implant-supported overdentures with various attachment systems: A 20-year retrospective study

    Directory of Open Access Journals (Sweden)

    Hao-Sheng Chang

    2015-03-01

    Conclusion: The overall survival rate of dental implants with overdenture rehabilitation was 95.3% (91.3% in maxillae vs. 96.4% in mandibles within the past 20 years. With careful treatment planning, implant-supported overdenture is an interesting treatment alternative with better esthetic, retention, stability, and good hygienic maintenance for patients with severe ridge resorption.

  2. Long-term survival of indirect pulp treatment performed in primary and permanent teeth with clinically diagnosed deep carious lesions

    NARCIS (Netherlands)

    Gruythuysen, R.; van Strijp, G.; Wu, M.K.

    2010-01-01

    Introduction: This retrospective study examined clinically and radiographically the 3-year survival of teeth treated with indirect pulp treatment (IPT) performed between 2000 and 2004. Methods: Sixty-six uncooperative children (4-18 years old) with at least one tooth with clinically diagnosed deep

  3. Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial

    NARCIS (Netherlands)

    Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

    2017-01-01

    BACKGROUND: Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been

  4. Factors impacting short and long-term kidney graft survival: modification by single intra-operative -high-dose induction with ATG-Fresenius.

    Science.gov (United States)

    Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

    2011-01-01

    A majority of recipients benefited from the intra-operative single high-dose induction (HDI) with ATG-Fresenius (ATG-F) still leaving a group of recipients who did not profit from this kind of induction. Therefore the aim of this retrospective analysis was 1st to identify the risk factors impacting short and long-term graft survival, and 2nd to assess the efficacy of this type of induction in kidney graft recipients with or without these risk factors. A total of 606 recipients receiving two different immunosuppressive treatment regimens (1st: Triple drug therapy [TDT, n=196] consisting mainly of steroids, azathioprine and cyclosporine; 2nd: TDT + 9 mg/kg ATG-F intra-operatively [HDI, n=410]) were included in this analysis and grouped according to their kidney graft survival time (short GST: ≤1 yr, n=100 and long GST: >5 yrs, n=506). The main risk factors associated with a shortened graft survival were pre-transplant sensitization, re-transplantation, rejections (in particular vascular or mixed ones) and the necessity of a long-term anti-rejection therapy. Adding ATG-F single high dose induction to TDT was more efficient in prolonging kidney graft survival than TDT alone not only in recipients without any risk factors (p<0.005) but also in recipients with at least one risk factor (p<0.021). Only in 4.6% of recipients having two or more risk factors this effect could not be demonstrated. The intra-operative single high-dose induction with ATG-F significantly improves the kidney graft survival in recipients with or without risk factors and can therefore be recommended.

  5. [LONG-TERM SURVIVAL OF DUAL DISORDERS PATIENTS AFTER MIXED CARE IN DUAL DISORDERS AND STANDARD WARDS VERSUS CARE ONLY IN DUAL DISORDERS WARD].

    Science.gov (United States)

    Gimelfarb, Yuri; Wolf, Aviva; Ben-Tzarfati, Mashit

    2017-01-01

    Dual disorders (co-occurring mental illness and substance abuse disorders in the same person) are extremely common among patients receiving mental health services. Integrated treatment has been proposed as the standard of care and it describes a flexible combination of treatments from the mental health and addiction fields that are blended together in the therapy. Scientific evidence for survival of dual disorders patients (DDPs), who had integrated dual disorders inpatient care, is lacking. To determine the long term survival rates following integrated care (Integrated Dual Diagnosis Treatment Ward [IDDTW] only) versus mixed care (IDDTW and psychiatric wards) during the life-time of DDPs. The charts of 333 subjects admitted to IDDTW during the period January 2002 - June 2006 were assessed at least 8 years after the first admission. Psychiatric diagnoses have been established and grouped according to international classification of diseases and health-related problems -10th edition (ICD-10). The Kaplan-Meier survival analysis was used to estimate the cumulative survival rates in all the subpopulations, and the predictive values of different variables were assessed by Cox proportional-hazards regression model. The total all-cause 12-year, unadjusted mortality was 21.1% in integrated care versus 24.6% in mixed care (pintegrated care as a predictive factor for all-cause mortality. The findings showed that there was no consistent evidence to support integrated inpatient care over mixed care, as measured by long-term survival. More studies are required in order to address the challenges posed in the treatment of DDPs.

  6. Survival and cause of death after traumatic spinal cord injury. A long-term epidemiological survey from Denmark

    DEFF Research Database (Denmark)

    Hartkopp, A; Brønnum-Hansen, Henrik; Seidenschnur, A M

    1997-01-01

    Life expectancy among individuals with spinal cord injuries (SCI) has remained lower than in the normal population, even with optimal medical management. But significant improvement has been achieved, as will be illustrated in this retrospective study of an unselected group of traumatic survivors...... treatment and were rehabilitated at the centre for Spinal Cord Injured in Hornbaek, Denmark. At the end of the follow-up, 31st December 1992, 236 (197 men and 39 women) had died. The commonest causes of death were lung diseases, particularly pneumonia; suicide; and ischaemic heart disease. Among...... and pneumonia. A significant decrease in the overall mortality was observed from the first (1953-1973) to the second half of the observation period (1972-1992). Similarly the survival curves for both men and women demonstrate that the gap in survival probability between the normal population and the SCI has...

  7. [Long-term outcome with end-stage renal disease - survival is not enough: does dialysis or kidney transplantation matter?].

    Science.gov (United States)

    Schulz, K-H; Thaiss, F

    2012-04-01

    Patients with end-stage renal disease require renal replacement therapy with either dialysis or kidney transplantation. Survival and quality of life (QoL) after transplantation are superior to chronic dialysis. Early living donor kidney transplantation is best for patient and graft survival. Preemptive living-related kidney transplantation therefore is the best medical treatment option for these patients. Patients with end-stage renal disease suffer from multiple physical and psychological complaints. The prevalence of depressive disorders is 20-25% in this population. Studies on QoL in children after kidney transplantation show a reduced physical QoL, but an overall good psychological QoL. Alarming results of numerous studies are the high non-adherence rates in adolescents. Especially exercise interventions during dialysis and after kidney transplantation show promising results. Whether QoL of patients will improve with new approaches to immunosuppressive therapy remains to be evaluated in future studies.

  8. Impact of immune parameters on long-term survival in metastatic renal cell      carcinoma

    DEFF Research Database (Denmark)

    Donskov, Frede; Maase, Hans von der

    2006-01-01

    with estimated       5-year survival rates of 60%, 25%, and 0%, respectively. These findings       were apparent in both our own prognostic model and in an extended Memorial       Sloan-Kettering Cancer Center (New York, NY) prognostic model. CONCLUSION:       This study points on five clinical and three...

  9. Application of the BAR score as a predictor of short- and long-term survival in liver transplantation patients.

    Science.gov (United States)

    de Campos Junior, Ivan Dias; Stucchi, Raquel Silveira Bello; Udo, Elisabete Yoko; Boin, Ilka de Fátima Santana Ferreira

    2015-01-01

    The balance of risk (BAR) is a prediction system after liver transplantation. To assess the BAR system, a retrospective observational study was performed in 402 patients who had transplant surgery between 1997 and 2012. The BAR score was computed for each patient. Receiver operating characteristic curve analysis with the Hosmer-Lemeshow test was used to calculate sensitivity, specificity, and model calibration. The cutoff value with the best Youden index was selected. Statistical analysis employed the Kaplan-Meier method (log-rank test) for survival, the Mann-Whitney test for group comparison, and multiple logistic regression analysis. 3-month survival was 46% for BAR ≥ 11 and 77% for BAR BAR ≥ 11 and 69% for BAR BAR ≥ 11 [odds ratio (OR) 3.08; 95% confidence interval (CI) 1.75-5.42; p = 0.001] and intrasurgical use of packed red blood cells (RBC) above 6 units (OR 4.49; 95% CI 2.73-7.39; p = 0.001). For survival BAR ≥ 11 (OR 2.94; 95% CI 1.67-5.16; p = 0.001) and RBC >6 units (OR 2.99; 95% CI 1.92-4.64; p = 0.001). Our study contributes to the incorporation of the BAR system into Brazilian transplantation centers.

  10. LONG-TERM PRECONDITIONING OF PLANTLETS: A PRACTICAL METHOD FOR ENHANCING SURVIVAL OF PINEAPPLE (Ananas comosus Merr.) SHOOT TIPS CRYOPRESERVED USING VITRIFICATION.

    Science.gov (United States)

    Hu, W H; Liu, S F; Liaw, S I

    2015-01-01

    The purpose of this study was to develop an efficient cryopreservation protocol for pineapple (Ananas comosus Merr.) shoot tips. The optimal state of pineapple plantlets was investigated by using sucrose preconditioning to enhance survival after cryostorage. To achieve a suitable state of plantlets before cryopreservation, 0.2 M to 0.4 M sucrose concentrations combined with short- (0-7 days), medium- (15-30 days), and long-term (75-150 days) preconditioning periods were compared. The highest survival (100 %) was achieved using the following procedure: intact plantlets underwent long-term preconditioning with 0.2 M sucrose for 135 days, dissected shoot tips were treated with a loading solution containing 2.0 M glycerol + 0.4 M sucrose for 60 min at 25 degree and the shoot tips were dehydrated in PVS2 for 2h at 0 degree C before being plunged in liquid nitrogen. Rewarming was conducted in a water-bath for 30 s at 40 degree C and PVS2 was replaced with a 1.2 M sucrose solution for 30 min at 25 degree C. The shoot tips were transferred on semisolid medium and left in the dark for 1 week, then in dim light for 3 weeks.

  11. Genetic Polymorphisms in Endothelin-1 as Predictors for Long-Term Survival and the Cardiac Index in Patients Undergoing On-Pump Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Ashham Mansur

    Full Text Available Genetic variants within the endothelin-1 gene (EDN1 have been associated with several cardiovascular diseases and may act as genetic prognostic markers. Here, we explored the overall relevance of EDN1 polymorphisms for long-term survival in patients undergoing on-pump cardiac surgery. A prospectively collected cohort of 455 Caucasian patients who underwent cardiac surgery with cardiopulmonary bypass was followed up for 5 years. The obtained genotypes and inferred haplotypes were analyzed for their associations with the five-year mortality rate (primary endpoint. The EDN1 T-1370G and K198N genotype distributions did not deviate from Hardy-Weinberg equilibrium and the major allele frequencies were 83% and 77%, respectively. The cardiovascular risk factors were equally distributed in terms of the different genotypes and haplotypes associated with the two polymorphisms. The five-year mortality rate did not differ among the different EDN1 T-1370G and K198N genotypes and haplotypes. Haplotype analysis revealed that carriers of the G-T (compound EDN1 T-1370G G/K198N T haplotype had a higher cardiac index than did non-carriers (p = 0.0008; however, this difference did not reach significance after adjusting for multiple testing. The results indicate that common variations in EDN1 do not act as prognostic markers for long-term survival in patients undergoing on-pump cardiac surgery.

  12. Long-term outcome of elderly patients requiring intensive care admission for abdominal pathologies: survival and quality of life.

    Science.gov (United States)

    Merlani, P; Chenaud, C; Mariotti, N; Ricou, B

    2007-05-01

    Medical developments have allowed the management of patients aged over 70 years with severe abdominal pathologies requiring intensive care unit (ICU) admission. These patients require enhanced life support and present a high ICU mortality. We investigated the outcome and quality of life (QOL) of elderly patients 2 years after their ICU stay for abdominal pathologies. Patients aged 70 years or over with abdominal pathologies, admitted to our ICU over a period of 2 years, were included. Two years following their ICU stay, a letter informed the patients about the present study. Consent to participate was obtained by telephone. QOL was assessed by the Euro-QOL and Short Form-36 questionnaires. Other patient-centered outcomes were evaluated. Overall, 2780 patients were admitted to the ICU during the study period; 141 (5%) patients were eligible; 112 of the 141 (79%) survived their ICU stay, 95 (67%) survived their hospital stay and 52 (37%) were alive 2 years after their ICU stay; 36 of the 52 survivors (69%) answered the questionnaire. Their QOL 2 years after their ICU stay was decreased in comparison with an age-matched population. Eighty-one per cent of patients lived at home and 57% were totally independent. They perceived their ICU stay as positive and 75% stated that they would agree to go through intensive care again. Factors associated with 2-year survival were the absence of co-morbidity, absence of malignancy and a lower Simplified Acute Physiology II score on ICU admission. A high mortality rate and a decrease in QOL were observed in elderly patients with severe abdominal pathologies. Nonetheless, these patients were able to adapt well to their physical disabilities.

  13. Follicular thyroid cancer in children and adolescents. Clinicopathologic features, long-term survival, and risk factors for recurrence

    International Nuclear Information System (INIS)

    Enomoto, Keisuke; Enomoto, Yukie; Uchino, Shinya; Yamashita, Hiroto; Noguchi, Shiro

    2013-01-01

    Children and adolescents represent 1-1.5% of all patients with thyroid cancer (TC). The vast majority of TC in children and adolescents is papillary TC; follicular TC (FTC) is exceedingly rare. In this study, we evaluate the clinical and pathological features of FTC in children and adolescents. We also report the risk factors for post-operative tumor recurrence and the associated outcomes. Twenty children and adolescents (under 21 years old) with FTC have been treated and followed at Noguchi Thyroid Clinic and Hospital Foundation since 1946. All patients underwent surgery (lobectomy, 11; subtotal thyroidectomy, 8; and total thyroidectomy, 1), and 8 patients received postoperative external beam radiation therapy. The incidence of FTC in children and adolescents was 1.9% among all FTC patients treated in our hospital. Histopathology revealed vascular and capsular invasion in 9 and 20 patients, respectively. The tumor recurrence rate in FTC with vascular invasion is significantly higher than in those without it (p=0.038). No other factors were significant. Patients with recurrences were treated with completion thyroidectomy and 131 I radioactive iodine therapy. There were no significant differences in the rates of disease-free survival or cause-specific survival when pediatric/adolescent FTC patients were compared to adults with FTC. FTC is very rare among children and adolescents, but the outcomes are similar to those observed among adults. Vascular invasion is poor prognostic indicator in pediatric/adolescent FTC patients. (author)

  14. Long-term in vivo survival of Rh(D)-negative donor red cells in a patient with anti-LW

    International Nuclear Information System (INIS)

    Chaplin, H.; Hunter, V.L.; Rosche, M.E.; Shirey, R.S.

    1985-01-01

    The present study documents immediate and long-term survival of crossmatch-incompatible Rh(D)-negative donor red cells in a patient with anti-LW. A 67-year-old group A Rh(D)-positive man was admitted for urgent coronary artery bypass surgery. The direct antiglobulin test (DAT) was weakly positive in two of five laboratories. His serum contained anti-LW (two laboratories); his red cells were LW negative (three antisera). Two siblings were LW-positive. Surgery was delayed, and 3 ml Rh(D)-negative crossmatch-incompatible red cells stored in citrate-phosphate-dextrose-adenine-one were labeled with 25 microCi of 51 Cr and injected. Immediate survival was approximately 100 percent with 92 percent survival at 20 hours. Six daily blood samples showed a decreased red cell lifespan, (T 1/2 . 14 days). Because of medical complications, 4 units of Rh(D)-negative crossmatch-incompatible blood were then transfused without clinical or hemolytic reaction. The anti-IgG DAT became stronger. In vivo survival of the remaining 51 Cr-RBCs became normal (T 1/2 28 days over the succeeding 20 days). Following transfusion, no change in serum antibody strength was demonstrated by double-blind titration of seven coded samples. The observations support modest reduction of lifespan for 3 ml of LW-positive red cells, but normal survival following subsequent transfusion of approximately 700 ml of LW-positive red cells

  15. SPARC, FOXP3, CD8 and CD45 correlation with disease recurrence and long-term disease-free survival in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Angela Chew

    Full Text Available BACKGROUND: SPARC is a matricellular protein involved in tissue remodelling, cell migration and angiogenesis, while forkhead box P3 (FOXP3 protein functions as a transcription factor involved in immune cell regulation. Both SPARC and FOXP3 can play an anti-tumorigenic role in cancer progression. The aim was to determine if SPARC, FOXP3, CD8 and CD45RO expression levels are associated with colorectal cancer (CRC stage, disease outcome and long-term cancer-specific survival (CSS in stage II and III CRC. METHODS AND FINDINGS: SPARC expression was initially assessed in 120 paired normal and stage I-IV CRCs. Subsequently, approximately 1000 paired patient samples of stage II or III CRCs in tissue microarrays were stained for SPARC, FOXP3, CD8 or CD45RO. Proportional hazards modelling assessed correlations between these markers and clinicopathological data, including disease outcome and cancer specific survival (CSS. Both SPARC and FOXP3 expression were significantly greater in CRC than normal colon (p<0.0001. High SPARC expression correlated with good disease outcome (≥60 mths without disease recurrence, p = 0.0039 and better long-term CSS in stage II CRC (<0.0001. In stage III CRC, high SPARC expression correlated with better long-term CSS (p<0.0001 and less adjuvant chemotherapy use (p = 0.01. High FOXP3 correlated with a good disease outcome, better long-term CSS and less adjuvant chemotherapy use in stage II (p<0.0037, <0.0001 and p = 0.04 respectively, but not in stage III CRC. High CD8 and CD45RO expression correlated with better disease outcome in stage II CRC, and better CSS, but the differences were not as marked as for SPARC and FOXP3. CONCLUSIONS: These data suggest that high SPARC and FOXP3 are associated with better disease outcome in stage II CRC and may be prognostic indicators of CSS. Further assessment of whether these markers predict patients at high risk of recurrence with stage II CRC and functional studies of these

  16. Enhanced left ventricular mass regression after aortic valve replacement in patients with aortic stenosis is associated with improved long-term survival.

    Science.gov (United States)

    Ali, Ayyaz; Patel, Amit; Ali, Ziad; Abu-Omar, Yasir; Saeed, Amber; Athanasiou, Thanos; Pepper, John

    2011-08-01

    Aortic valve replacement in patients with aortic stenosis is usually followed by regression of left ventricular hypertrophy. More complete resolution of left ventricular hypertrophy is suggested to be associated with superior clinical outcomes; however, its translational impact on long-term survival after aortic valve replacement has not been investigated. Demographic, operative, and clinical data were obtained retrospectively through case note review. Transthoracic echocardiography was used to measure left ventricular mass preoperatively and at annual follow-up visits. Patients were classified according to their reduction in left ventricular mass at 1 year after the operation: group 1, less than 25 g; group 2, 25 to 150 g; and group 3, more than 150 g. Kaplan-Meier and multivariable Cox regression were used. A total of 147 patients were discharged from the hospital after aortic valve replacement for aortic stenosis between 1991 and 2001. Preoperative left ventricular mass was 279 ± 98 g in group 1 (n = 47), 347 ± 104 g in group 2 (n = 62), and 491 ± 183 g in group 3 (n = 38) (P regression such as ischemic heart disease or hypertension, valve type, or valve size used. Ten-year actuarial survival was not statistically different in patients with enhanced left ventricular mass regression when compared with the log-rank test (group 1, 51% ± 9%; group 2, 54% ± 8%; and group 3, 72% ± 10%) (P = .26). After adjustment, left ventricular mass reduction of more than 150 g was demonstrated as an independent predictor of improved long-term survival on multivariate analysis (P = .02). Our study is the first to suggest that enhanced postoperative left ventricular mass regression, specifically in patients undergoing aortic valve replacement for aortic stenosis, may be associated with improved long-term survival. In view of these findings, strategies purported to be associated with superior left ventricular mass regression should be considered when undertaking

  17. Rate of primary refractory disease in B and T-cell non-Hodgkin's lymphoma: correlation with long-term survival.

    Directory of Open Access Journals (Sweden)

    Corrado Tarella

    Full Text Available BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL. This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%, intensive therapy with autograft (16.9%, or other therapies (19.9%. Among B-cell NHL, 1,356 (47.8% received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2% patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001. Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001. Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001. CONCLUSION: Chemosensitivity to primary

  18. Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases

    Directory of Open Access Journals (Sweden)

    Daniel eGorovets

    2015-05-01

    Full Text Available Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT in patients with brain metastases treated with stereotactic radiosurgery (SRS as their initial radiotherapy approach. Material and Methods: Patients with brain metastases treated with SRS from 2001-2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky Performance Status ≥70, and life expectancy ≥3 mo. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-yr WBRT-free survival (N=104, and those who died or required salvage WBRT within 3 mo of SRS (N=56. Differences between these groups were assessed by univariate and multivariate analyses.Results: Median survival for all patients was 11 mo. Among patients with ≥1-yr WBRT-free survival, median survival was 33 mo [12-107 mo] with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p<0.05 included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions. After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival.Conclusions: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.

  19. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna

    International Nuclear Information System (INIS)

    Sarapultseva, Elena I.; Dubrova, Yuri E.

    2016-01-01

    The results of recent studies have provided strong evidence for the transgenerational effects of parental exposure to ionising radiation and chemical mutagens. However, the transgenerational effects of parental exposure on survival and fertility remain poorly understood. To establish whether parental irradiation can affect the survival and fertility of directly exposed organisms and their offspring, crustacean Daphnia magna were given 10, 100, 1000 and 10,000 mGy of acute γ-rays. Exposure to 1000 and 10,000 mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. The fertility of F 0 and F 1 Daphnia gradually declined with the dose of parental exposure and significantly decreased at dose of 100 mGy and at higher doses. The effects of parental irradiation on the number of broods were only observed among the F 0 Daphnia exposed to 1000 and 10,000 mGy, whereas the brood size was equally affected in the two consecutive generations. In contrast, the F 2 total fertility was compromised only among progeny of parents that received the highest dose of 10,000 mGy. We propose that the decreased fertility observed among the F 2 progeny of parents exposed to 10,000 mGy is attributed to transgenerational effects of parental irradiation. Our results also indicate a substantial recovery of the F 2 progeny of irradiated F 0 Daphnia exposed to the lower doses of acute γ-rays. - Highlights: • Viability of irradiated daphnids and their F 1 progeny is compromised. • Viability of the F 2 progeny of irradiated parents is not affected. • Total fertility of irradiated daphnids and their F 1 progeny declines with the dose. • Total fertility of the F 2 progeny of parents exposed to 10,000 mGy is compromised. • The decreased fertility among the F 2 progeny is transgenerational phenomenon.

  20. Long-term cumulative survival and mechanical complications of single-tooth Ankylos Implants: focus on the abutment neck fractures.

    Science.gov (United States)

    Shim, Hye Won; Yang, Byoung-Eun

    2015-12-01

    To evaluate the cumulative survival rate (CSR) and mechanical complications of single-tooth Ankylos® implants. This was a retrospective clinical study that analyzed 450 single Ankylos® implants installed in 275 patients between December 2005 and December 2012. The main outcomes were survival results CSR and implant failure) and mechanical complications (screw loosening, fracture, and cumulative fracture rate [CFR]). The main outcomes were analyzed according to age, sex, implant length or diameter, bone graft, arch, and position. The 8-year CSR was 96.9%. Thirteen (2.9%) implants failed because of early osseointegration failure in 3, marginal bone loss in 6, and abutment fracture in 4. Screw loosening occurred in 10 implants (2.2%), and 10 abutment fractures occurred. All abutment fractures were located in the neck, and concurrent screw fractures were observed. The CSR and rate of screw loosening did not differ significantly according to factors. The CFR was higher in middle-aged patients (5.3% vs 0.0% in younger and older patients); for teeth in a molar position (5.8% vs 0.0% for premolar or 1.1% for anterior position); and for larger-diameter implants (4.5% for 4.5 mm and 6.7% for 5.5 mm diameter vs 0.5% for 3.5 mm diameter) (all Pabutment fractures (2.2%) were observed and some fractures resulted in implant failures. Middle-aged patients, the molar position, and a large implant diameter were associated with a high incidence of abutment fracture.

  1. Incidence, recurrence, and long-term survival of ischemic stroke subtypes: A population-based study in the Middle East.

    Science.gov (United States)

    Saber, Hamidreza; Thrift, Amanda G; Kapral, Moira K; Shoamanesh, Ashkan; Amiri, Amin; Farzadfard, Mohammad T; Behrouz, Réza; Azarpazhooh, Mahmoud Reza

    2017-10-01

    Background Incidence, risk factors, case fatality and survival rates of ischemic stroke subtypes are unknown in the Middle East due to the lack of community-based incidence stroke studies in this region. Aim To characterize ischemic stroke subtypes in a Middle Eastern population. Methods The Mashad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. We identified 512 cases of first-ever ischemic stroke [264 men (mean age 65.5 ± 14.4) and 248 women (mean age 64.14 ± 14.5)]. Subtypes of ischemic stroke were classified according to the TOAST criteria. Incidence rates were age standardized to the WHO and European populations. Results The proportion of stroke subtypes was distributed as follows: 14.1% large artery disease, 15% cardioembolic, 22.5% small artery disease, 43.9% undetermined and 4.5% other. The greatest overall incidence rates were attributed to undetermined infarction (49.97/100,000) followed by small artery disease (25.54/100,000). Prevalence of hypertension, diabetes and atrial fibrillation differed among ischemic stroke subtypes. Overall, there were 268 (52.34%) deaths and 73 (14.25%) recurrent strokes at five years after incident ischemic stroke, with the greatest risk of recurrence seen in the large artery disease (35.6%) and cardioembolic (35.5%) subgroups. Survival was similar in men and women for each stroke subtype. Conclusions We observed markedly greater incidence rates of ischemic stroke subtypes than in other countries within the Mashad Stroke Incidence Study after age standardization. Our findings should be considered when planning prevention and stroke care services in this region.

  2. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna

    Energy Technology Data Exchange (ETDEWEB)

    Sarapultseva, Elena I. [Department of Biology, Institute of Nuclear Power Engineering NRNU MEPhI, Studgorodok,1, Obninsk, Kaluga Region 249040 (Russian Federation); National Research Nuclear University “MEPhI”, Kashirskoe Highway, 31, Moscow 115409 (Russian Federation); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina Str. 3, 11933 Moscow (Russian Federation)

    2016-10-15

    The results of recent studies have provided strong evidence for the transgenerational effects of parental exposure to ionising radiation and chemical mutagens. However, the transgenerational effects of parental exposure on survival and fertility remain poorly understood. To establish whether parental irradiation can affect the survival and fertility of directly exposed organisms and their offspring, crustacean Daphnia magna were given 10, 100, 1000 and 10,000 mGy of acute γ-rays. Exposure to 1000 and 10,000 mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. The fertility of F{sub 0} and F{sub 1}Daphnia gradually declined with the dose of parental exposure and significantly decreased at dose of 100 mGy and at higher doses. The effects of parental irradiation on the number of broods were only observed among the F{sub 0}Daphnia exposed to 1000 and 10,000 mGy, whereas the brood size was equally affected in the two consecutive generations. In contrast, the F{sub 2} total fertility was compromised only among progeny of parents that received the highest dose of 10,000 mGy. We propose that the decreased fertility observed among the F{sub 2} progeny of parents exposed to 10,000 mGy is attributed to transgenerational effects of parental irradiation. Our results also indicate a substantial recovery of the F{sub 2} progeny of irradiated F{sub 0}Daphnia exposed to the lower doses of acute γ-rays. - Highlights: • Viability of irradiated daphnids and their F{sub 1} progeny is compromised. • Viability of the F{sub 2} progeny of irradiated parents is not affected. • Total fertility of irradiated daphnids and their F{sub 1} progeny declines with the dose. • Total fertility of the F{sub 2} progeny of parents exposed to 10,000 mGy is compromised. • The decreased fertility among the F{sub 2} progeny is transgenerational phenomenon.

  3. Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients

    Energy Technology Data Exchange (ETDEWEB)

    Xu, H.-X. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Lu, M.-D. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xie, X.-Y. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Yin, X.-Y. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Kuang, M. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, J.-W. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Z.-F. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, G.-J. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

    2005-09-01

    AIM: To identify prognostic factors for long-term outcome for patients with hepatocellular carcinoma (HCC) after percutaneous microwave or radiofrequency ablation. MATERIALS AND METHODS: In total, 137 consecutive patients with HCC underwent microwave or radiofrequency ablation with curative intent; 16 possible prognostic factors were evaluated for their association with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analysis. RESULTS: The median OS and DFS were 27.0 months and 8.2 months, respectively. OS rates for all patients at 1, 2, 3, 4 and 5 years were 73.9%, 52.1%, 42.8%, 26.2% and 20.1%, respectively. DFS rates at 1, 2, 3 and 4 years were 38.1%, 21.9%, 18.8%, and 14.1%, respectively. Pretreatment serum alpha-fetoprotein (AFP) >200 ng/ml, pretreatment serum albumin {<=}35 g/dl, liver function Child's class C and incomplete ablation were found to be significant predictors for OS by univariate analysis. Using multivariate analysis, incomplete ablation was identified to be the most significant independent predictor for OS. Other independent predictors for OS were serum albumin level, serum AFP level and Child-Pugh classification. Recurrence after hepatectomy and prothrombin time >14 s were identified to be significant predictors for DFS by univariate analysis, and the former was the only independent predictor for DFS by multivariate analysis. CONCLUSION: Prognosis for patients with HCC after thermal ablation with curative intent was determined by treatment response to ablation, pretreatment serum AFP, and liver function reserve. Tumour response to treatment was the most predictive factor for long-term survival and was related to tumour size, thus careful selection of patients for ablation therapy is recommended.

  4. Recurrence-free survival, but not surgical therapy per se, determines 583 patients' long-term satisfaction following primary pilonidal sinus surgery.

    Science.gov (United States)

    Doll, Dietrich; Luedi, Markus M; Evers, Theo; Kauf, Peter; Matevossian, Edouard

    2015-05-01

    With pilonidal sinus disease (PSD) incidence increasing and patients freely choosing their surgeon, patients' interest issues have been brought forward estimating patient satisfaction following pilonidal sinus surgery. The influence of wound healing time and long-term recurrence rate on patient satisfaction in primary PSD surgery has not been investigated yet. Five hundred eighty-three patients (German military cohort) were interviewed, compiling wound healing time, aesthetic satisfaction, long-term recurrence-free survival and patient satisfaction having undergone primary open (PO) treatment, marsupialization (MARS) or primary midline closure (PMC) treatment. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. Patient satisfaction ranking from 1 to 10 (10 = max. satisfied) showed an average satisfaction of 8.2 (range 0-10; 95% confidence interval (CI) 7891-8250). In-hospital stay time was significantly longer in primary open (PO) and marsupialization (MARS) group as compared to primary midline closure (PMC; p < 0.0001, Kruskal-Wallis test). Satisfaction was comparable between treatment groups, and was neither linked to in-hospital stay time nor to longer outpatient wound care period or total treatment time. Recurrence-free survival, as seen in the PO and PMC treatment group, revealed a highly significant difference for all patients. Improvement in MARS patients with versus without recurrence was low, as satisfaction with primary treatment was lower as the other groups. Neither choice of surgical treatment nor treatment duration within hospital or after hospital influences patient satisfaction, as long as recurrence-free survival can be provided. Marsupialization was ranked lower in both groups (with or without recurrence), and should be abandoned, as patients are significantly less satisfied with either results, independent of recurrence.

  5. Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow

    International Nuclear Information System (INIS)

    Longley, R.E.; Good, R.A.

    1986-01-01

    The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras

  6. Radiation-induced myelopathy in long-term surviving metastatic spinal cord compression patients after hypofractionated radiotherapy: a clinical and magnetic resonance imaging analysis

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; Bellavita, Rita; Floridi, Piero; Celani, Grazia; Righetti, Enrico; Lupattelli, Marco; Panizza, Bianca Moira; Frattegiani, Alessandro; Pelliccioli, Gian Piero; Latini, Paolo

    2001-01-01

    Background and purpose: Hypofractionated radiotherapy is often administered in metastatic spinal cord compression (MSCC), but no studies have been published on the incidence of radiation-induced myelopathy (RIM) in long-term surviving patients. Our report addresses this topic. Patients and methods: Of 465 consecutive MSCC patients submitted to radiotherapy between 1988 and 1997, 13 live patients (seven females, six males, median age 69 years, median follow-up 69 months) surviving for 2 years or more were retrospectively reviewed to evaluate RIM. All patients underwent radiotherapy. Eight patients underwent a short-course regimen of 8 Gy, with 7 days rest, and then another 8 Gy. Five patients underwent a split-course regimen of 5 Gy x3, 4 days rest, and then 3 Gy x5. Only one patient also underwent laminectomy. Full neurological examination and magnetic resonance imaging (MRI) were performed. Results: Of 12 patients submitted to radiotherapy alone, 11 were ambulant (eight without support and three with support) with good bladder function. In nine of these 11 patients, MRI was negative; in one case MRI evidenced an in-field relapse 30 months after the end of radiotherapy, and in the other, two new MSCC foci outside the irradiated spine. In the remaining patient RIM was suspected at 18 months after radiotherapy when the patient became paraplegic and cystoplegic, and magnetic resonance images evidenced an ischemic injury in the irradiated area. The only patient treated with surgery plus postoperative radiotherapy worsened and remained paraparetic. Magnetic resonance images showed cord atrophy at the surgical level, explained as an ischemic necrosis due to surgery injury. Conclusions: On the grounds of our data regarding RIM in long-term surviving MSCC patients, we believe that a hypofractionated radiotherapy regimen can be used for the majority of patients. For a minority of patients, more protracted radiation regimens could be considered

  7. Long-term survival of Naegleria polaris from Antarctica after 10 years of storage at 4 °C.

    Science.gov (United States)

    Matsuo, Junji; Nakamura, Shinji; Okubo, Torahiko; Fukui, Manabu; Yamaguchi, Hiroyuki

    2018-03-01

    A free-living amoeba, Naegleria is ubiquitously distributed in various natural environments. Since some Naegleria spp. are exclusively distributed in the Arctic and sub-Antarctic regions, we hypothesized that the amoeba may be useful to determine long-term survival of Naegleria in laboratory conditions at 4 °C. The main objective of the study is to determine that a species of an environmental amoebal isolated can live at low temperatures after a long time. Here, we therefore show long-term survival of an amoeba, Naegleria polaris isolated from a sediment sample, which was collected from Antarctica 10 years ago, and since stored at 4 °C. The sample was put on non-nutrient agar plates with heat-killed Escherichia coli, and then the plate was incubated at 4, 15, or 30 °C. Motile amoebae were seen only when the plate was incubated at 15 °C. The sequencing of ribosomal DNA including internal transcribed spacers (ITS) 1, 5.8S rDNA, and ITS2 region revealed the amoebae to be N. polaris, which is exclusively distributed in the Arctic and sub-Antarctic regions. Scanning electron microscopic observation showed that no typical sucker-like structure was seen on the surface of N. polaris, but the cysts were similar to those of Naegleria fowleri. Thus, our result shows, for the first time, that N. polaris can survive after 10 years of storage at 4 °C. This finding may help us understand the still undescribed effects of environmental samples on viability of amoebae.

  8. Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients

    International Nuclear Information System (INIS)

    Xu, H.-X.; Lu, M.-D.; Xie, X.-Y.; Yin, X.-Y.; Kuang, M.; Chen, J.-W.; Xu, Z.-F.; Liu, G.-J.

    2005-01-01

    AIM: To identify prognostic factors for long-term outcome for patients with hepatocellular carcinoma (HCC) after percutaneous microwave or radiofrequency ablation. MATERIALS AND METHODS: In total, 137 consecutive patients with HCC underwent microwave or radiofrequency ablation with curative intent; 16 possible prognostic factors were evaluated for their association with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analysis. RESULTS: The median OS and DFS were 27.0 months and 8.2 months, respectively. OS rates for all patients at 1, 2, 3, 4 and 5 years were 73.9%, 52.1%, 42.8%, 26.2% and 20.1%, respectively. DFS rates at 1, 2, 3 and 4 years were 38.1%, 21.9%, 18.8%, and 14.1%, respectively. Pretreatment serum alpha-fetoprotein (AFP) >200 ng/ml, pretreatment serum albumin ≤35 g/dl, liver function Child's class C and incomplete ablation were found to be significant predictors for OS by univariate analysis. Using multivariate analysis, incomplete ablation was identified to be the most significant independent predictor for OS. Other independent predictors for OS were serum albumin level, serum AFP level and Child-Pugh classification. Recurrence after hepatectomy and prothrombin time >14 s were identified to be significant predictors for DFS by univariate analysis, and the former was the only independent predictor for DFS by multivariate analysis. CONCLUSION: Prognosis for patients with HCC after thermal ablation with curative intent was determined by treatment response to ablation, pretreatment serum AFP, and liver function reserve. Tumour response to treatment was the most predictive factor for long-term survival and was related to tumour size, thus careful selection of patients for ablation therapy is recommended

  9. Long-term survivability of riprap for armoring uranium-mill tailings and covers: a literature review. [203 references

    Energy Technology Data Exchange (ETDEWEB)

    Lindsey, C.G.; Long, L.W.; Begej, C.W.

    1982-06-01

    Pacific Northwest Laboratory (PNL) is investigating the use of a rock armoring blanket (riprap) to mitigate wind and water erosion of an earthen radon suppression cover applied to uranium mill tailings. Because the radon suppression cover and the tailings must remain intact for up to 1000 years or longer, the riprap must withstand natural weathering forces. This report is a review of information on rock weathering and riprap durability. Chemical and physical weathering processes, rock characteristics related to durability, climatic conditions affecting the degree and rate of weathering, and testing procedures used to measure weathering susceptibilities have been reviewed. Sampling and testing techniques, as well as analyses of physical and chemical weathering susceptibilities, are necessary to evaluate rock durability. Many potential riprap materials may not be able to survive 1000 years of weathering. Available techniques for durability testing cannot adequately predict rock durability for the 1000-year period because they do not consider the issue of time (i.e., how long must riprap remain stable). This report includes an Appendix, which discusses rock weathering, written by Dr. Richard Jahns of Stanford University.

  10. Long-term survival of bladder preservation therapy with radiation and chemotherapy for locally invasive bladder cancer

    International Nuclear Information System (INIS)

    Noguchi, Sumio; Takase, Kazunori; Kubota, Yoshinobu; Masuda, Mitsunobu; Yao, Masahiro; Hosaka, Masahiko

    1998-01-01

    The prognoses and prognostic factors of the 54 patients with locally invasive bladder cancer who underwent bladder preservation therapy at Yokohama City University Hospital between 1977 and 1995 were analyzed statistically. The therapeutic modalities of bladder preservation were mainly radiation or chemotherapy. The prognosis for the patients who underwent bladder preservation therapy was worse than that for the patients who underwent total cystectomy. The prognostic factors of these patients were size and grade of tumor, presence of hydronephrosis and performance status (PS) of the patients by univariate analysis. Tumor grade was the most predictable prognostic factor using multivariate analysis. Only 17 patients survived more than 5 years after treatment; 78% of the survivors had good PS (0 or 1). Five of them died of cancer and two patients were alive with cancer. All of them had G3 tumors. These results suggest that patients with locally invasive G2 tumor could be candiates for bladder preservation therapy and patients who underwent bladder preservation therapy should be evaluated at 10 years post-therapy. (author)

  11. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.

    Directory of Open Access Journals (Sweden)

    Young-Mi Lim

    Full Text Available Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1 is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1 and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.

  12. Long-term survival after liver transplant for recurrent hepatocellular carcinoma with bile duct tumor thrombus: case report.

    Science.gov (United States)

    Liu, Chao; Wang, Jie

    2012-12-01

    Hepatocellular carcinoma with bile duct tumor thrombus is considered an aggressive malignancy, and the prognosis of liver transplant for it remains obscure. A 42-year-old man with recurrent hepatocellular carcinoma and a history of surgical resection was admitted to our hospital with a 10-day history of yellowish urine and itchy skin. There were 3 lesions in the right lobe with the diameter of 2 cm each. A mass was found in the upper part of common bile duct, and the intrahepatic bile duct was dilated. His serum alpha-fetoprotein level was 2476 μg/L, total bilirubin level was 327 μmol/L, direct bilirubin level was 261 μmol/L, and alanine aminotransferase was 714 U/L. There was no main portal vein thrombus or extrahepatic metastases. Because of his poor liver function, he was listed for a liver transplant. During the wait (30 d), he underwent 9 episodes of plasmapheresis to decrease the serum level of bilirubin. He had an orthotopic liver transplant with the graft from a deceased donor. After the liver transplant, he received 5 cycles of chemotherapy with the regimen of oxaliplatin and 5-fluorouracil. This patient has survived without recurrence of hepatocellular carcinoma for more than 82 months and remains in good condition. Liver transplant may have a favorable result for hepatocellular carcinoma patient with a bile duct tumor thrombus, within the Milan criteria.

  13. Long-term survivability of riprap for armoring uranium-mill tailings and covers: a literature review

    International Nuclear Information System (INIS)

    Lindsey, C.G.; Long, L.W.; Begej, C.W.

    1982-06-01

    Pacific Northwest Laboratory (PNL) is investigating the use of a rock armoring blanket (riprap) to mitigate wind and water erosion of an earthen radon suppression cover applied to uranium mill tailings. Because the radon suppression cover and the tailings must remain intact for up to 1000 years or longer, the riprap must withstand natural weathering forces. This report is a review of information on rock weathering and riprap durability. Chemical and physical weathering processes, rock characteristics related to durability, climatic conditions affecting the degree and rate of weathering, and testing procedures used to measure weathering susceptibilities have been reviewed. Sampling and testing techniques, as well as analyses of physical and chemical weathering susceptibilities, are necessary to evaluate rock durability. Many potential riprap materials may not be able to survive 1000 years of weathering. Available techniques for durability testing cannot adequately predict rock durability for the 1000-year period because they do not consider the issue of time (i.e., how long must riprap remain stable). This report includes an Appendix, which discusses rock weathering, written by Dr. Richard Jahns of Stanford University

  14. Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Winter, Stuart C; Stephenson, Sally-Anne; Subramaniam, Selva K; Paleri, Vinidh; Ha, Kien; Marnane, Conor; Krishnan, Suren; Rees, Guy

    2009-01-01

    Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further

  15. Splenectomy during whole liver transplantation: a morbid procedure which does not adversely impact long-term survival.

    Science.gov (United States)

    Golse, Nicolas; Mohkam, Kayvan; Rode, Agnès; Pradat, Pierre; Ducerf, Christian; Mabrut, Jean-Yves

    2017-06-01

    Indications for splenectomy (SP) during whole liver transplantation (LT) remain controversial and SP is often avoided because of common complications. We aimed to evaluate specific complications of these combined procedures. Data were retrospectively analysed. Splenectomy was performed in patients with splenorenal shunt and/or splenic artery aneurysms or hypersplenism. Patients undergoing simultaneous transplantation and splenectomy (LTSP group) were matched to a non-splenectomy group (LT group). Between 1994 and 2013, we included 47 and 94 patients in LTSP and LT groups, respectively. The LTSP patients had a higher rate of pre-LT portal vein thrombosis (PVT). The LTSP group had a longer operative time and greater blood loss. Mean follow-up was 101 months and 5-year survivals were identical (LTSP 85% vs LT 88%, p = 0.831). Hospital morbidity and rejection incidence were comparable, whereas de novo PVT (34% vs 2%, p Splenectomy during LT is technically demanding and exposes recipients to a higher thrombosis rate, therefore portal vein patency must be specifically assessed postoperatively. In selected recipients, SP can be performed without increased mortality but at the price of worsening outcome as evidenced by greater risk of infection and PVT. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  16. Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus

    Directory of Open Access Journals (Sweden)

    Natalia Avaliani

    2017-01-01

    Full Text Available Direct conversion of human somatic cells to induced neurons (iNs, using lineage-specific transcription factors has opened new opportunities for cell therapy in a number of neurological diseases, including epilepsy. In most severe cases of epilepsy, seizures often originate in the hippocampus, where populations of inhibitory interneurons degenerate. Thus, iNs could be of potential use to replace these lost interneurons. It is not known, however, if iNs survive and maintain functional neuronal properties for prolonged time periods in in vivo. We transplanted human fibroblast-derived iNs into the adult rat hippocampus and observed a progressive morphological differentiation, with more developed dendritic arborisation at six months as compared to one month. This was accompanied by mature electrophysiological properties and fast high amplitude action potentials at six months after transplantation. This proof-of-principle study suggests that human iNs can be developed as a candidate source for cell replacement therapy in temporal lobe epilepsy.

  17. Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

    Science.gov (United States)

    Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

    2012-01-01

    Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748

  18. Genome Wide Association Study for Predictors of Progression Free Survival in Patients on Capecitabine, Oxaliplatin, Bevacizumab and Cetuximab in First-Line Therapy of Metastatic Colorectal Cancer

    NARCIS (Netherlands)

    Pander, Jan; van Huis-Tanja, Lieke; Böhringer, Stefan; van der Straaten, Tahar; Gelderblom, Hans; Punt, Cornelis; Guchelaar, Henk-Jan

    2015-01-01

    Despite expanding options for systemic treatment, survival for metastatic colorectal cancer (mCRC) remains limited and individual response is difficult to predict. In search of pre-treatment predictors, pharmacogenetic research has mainly used a candidate gene approach. Genome wide association (GWA)

  19. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer

    Science.gov (United States)

    Park, Jun Seok; Sakai, Yoshiharu; Simon, NG Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

    2016-01-01

    Abstract Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer. An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate. The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively. Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

  20. The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors - results of a prospective study

    Directory of Open Access Journals (Sweden)

    Sullivan-Halley Jane

    2011-06-01

    Full Text Available Abstract Background Few data exist on survival or health-related quality of life (QOL related to herbal remedy use among long-term breast cancer survivors. The objective of this report is to examine whether herbal remedy use is associated with survival or the health-related QOL of these long-term breast cancer survivors. Methods In 1999-2000, we collected the information of herbal remedy use and QOL during a telephone interview with 371 Los Angeles Non-Hispanic/Hispanic white women who had survived more than 10 years after breast cancer diagnosis. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36 questionnaire. Patients were followed for mortality from the baseline interview through 2007. 299 surviving patients completed a second telephone interview on QOL in 2002-2004. We used multivariable Cox proportional hazards methods to estimate relative risks (RR and 95% confidence intervals (CI for mortality and applied multivariable linear regression models to compare average SF-36 change scores (follow-up - baseline between herbal remedy users and non-users. Results Fifty-nine percent of participants were herbal remedy users at baseline. The most commonly used herbal remedies were echinacea, herbal teas, and ginko biloba. Herbal remedy use was associated with non-statistically significant increases in the risks for all-cause (44 deaths, RR = 1.28, 95% CI = 0.62-2.64 and breast cancer (33 deaths, RR = 1.78, 95% CI = 0.72-4.40 mortality. Both herbal remedy users' and non-users' mental component summary scores on the SF-36 increased similarly from the first survey to the second survey (P = 0.16, but herbal remedy users' physical component summary scores decreased more than those of non-users (-5.7 vs. -3.2, P = 0.02. Conclusions Our data provide some evidence that herbal remedy use is associated with poorer survival and a poorer physical component score for health-related QOL among women who have survived breast cancer for at least

  1. Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium.

    Science.gov (United States)

    Blocki, Anna; Beyer, Sebastian; Dewavrin, Jean-Yves; Goralczyk, Anna; Wang, Yingting; Peh, Priscilla; Ng, Michael; Moonshi, Shehzahdi S; Vuddagiri, Susmitha; Raghunath, Michael; Martinez, Eliana C; Bhakoo, Kishore K

    2015-06-01

    The limited efficacy of cardiac cell-based therapy is thought to be due to poor cell retention within the myocardium. Hence, there is an urgent need for biomaterials that aid in long-term cell retention. This study describes the development of injectable microcapsules for the delivery of mesenchymal stem cells (MSCs) into the infarcted cardiac wall. These microcapsules comprise of low concentrations of agarose supplemented with extracellular matrix (ECM) proteins collagen and fibrin. Dextran sulfate, a negatively charged polycarbohydrate, was added to mimic glycosaminoglycans in the ECM. Cell viability assays showed that a combination of all components is necessary to support long-term survival and proliferation of MSCs within microcapsules. Following intramyocardial transplantation, microcapsules degraded slowly in vivo and did not induce a fibrotic foreign body response. Pre-labeling of encapsulated MSCs with iron oxide nanoparticles allowed continued cell-tracking by MRI over several weeks following transplantation into infarcted myocardium. In contrast, MSCs injected as cell suspension were only detectable for two days post transplantation by MRI. Histological analysis confirmed integration of transplanted cells at the infarct site. Therefore, microcapsules proved to be suitable for stem cell delivery into the infarcted myocardium and can overcome current limitations of poor cell retention in cardiac cell-based therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. The dark side of the moon: Impact of moon phases on long-term survival, mortality and morbidity of surgery for lung cancer

    Directory of Open Access Journals (Sweden)

    Kuehnl A

    2009-04-01

    Full Text Available Abstract Objective Superstition is common and causes discomfiture or fear, especially in patients who have to undergo surgery for cancer. One superstition is, that moon phases influence surgical outcome. This study was performed to analyse lunar impact on the outcome following lung cancer surgery. Methods 2411 patients underwent pulmonary resection for lung cancer in the past 30 years at our institution. Intra-and postoperative complications as well as long-term follow-up data were entered in our lung-cancer database. Factors influencing mortality, morbidity and survival were analyzed. Results Rate of intra-operative complications as well as rate of post-operative morbidity and mortality was not significantly affected by moon phases. Furthermore, there was no significant impact of the lunar cycle on long-term survial. Conclusion In this study there was no evidence that outcome of surgery for lung cancer is affected by the moon. These results may help the physician to quite the mind of patients who are somewhat afraid of wrong timing of surgery with respect to the moon phases. However, patients who strongly believe in the impact of moon phase should be taken seriously and correct timing of operations should be conceded to them as long as key-date scheduling doesn't constrict evidence based treatment regimens.

  3. Understanding cancer survivors' information needs and information-seeking behaviors for complementary and alternative medicine from short- to long-term survival: a mixed-methods study.

    Science.gov (United States)

    Scarton, Lou Ann; Del Fiol, Guilherme; Oakley-Girvan, Ingrid; Gibson, Bryan; Logan, Robert; Workman, T Elizabeth

    2018-01-01

    The research examined complementary and alternative medicine (CAM) information-seeking behaviors and preferences from short- to long-term cancer survival, including goals, motivations, and information sources. A mixed-methods approach was used with cancer survivors from the "Assessment of Patients' Experience with Cancer Care" 2004 cohort. Data collection included a mail survey and phone interviews using the critical incident technique (CIT). Seventy survivors from the 2004 study responded to the survey, and eight participated in the CIT interviews. Quantitative results showed that CAM usage did not change significantly between 2004 and 2015. The following themes emerged from the CIT: families' and friends' provision of the initial introduction to a CAM, use of CAM to manage the emotional and psychological impact of cancer, utilization of trained CAM practitioners, and online resources as a prominent source for CAM information. The majority of participants expressed an interest in an online information-sharing portal for CAM. Patients continue to use CAM well into long-term cancer survivorship. Finding trustworthy sources for information on CAM presents many challenges such as reliability of source, conflicting information on efficacy, and unknown interactions with conventional medications. Study participants expressed interest in an online portal to meet these needs through patient testimonials and linkage of claims to the scientific literature. Such a portal could also aid medical librarians and clinicians in locating and evaluating CAM information on behalf of patients.

  4. Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

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    Vargas, H.A.; Burger, I.A.; Micco, M.; Sosa, R.E.; Weber, W.; Hricak, H.; Sala, E. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Goldman, D.A. [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Chi, D.S. [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States)

    2015-11-15

    Our aim was to evaluate the associations between quantitative {sup 18}F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUV{sub max}), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUV{sub max} and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUV{sub max} was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. (orig.)

  5. Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

    International Nuclear Information System (INIS)

    Vargas, H.A.; Burger, I.A.; Micco, M.; Sosa, R.E.; Weber, W.; Hricak, H.; Sala, E.; Goldman, D.A.; Chi, D.S.

    2015-01-01

    Our aim was to evaluate the associations between quantitative 18 F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUV max ), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUV max and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUV max was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. (orig.)

  6. Predictors for contrast media-induced nephropathy and long-term survival: Prospectively assessed data from the randomized controlled Dialysis-Versus-Diuresis (DVD) trial

    Science.gov (United States)

    Hölscher, Birgit; Heitmeyer, Christine; Fobker, Manfred; Breithardt, Günter; Schaefer, Roland M; Reinecke, Holger

    2008-01-01

    patients’ long-term survival. PMID:18987758

  7. Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF.

    Science.gov (United States)

    Wong, Wai-Kai; Cheung, Anny Wan-Suen; Yu, Sau-Wai; Sha, Ou; Cho, Eric Yu Pang

    2014-10-01

    Different trophic factors are known to promote retinal ganglion cell survival and regeneration, but each had their own limitations. We report that hepatocyte growth factor (HGF) confers distinct advantages in supporting ganglion cell survival and axonal regeneration, when compared to two well-established trophic factors ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Ganglion cells in adult hamster were injured by cutting the optic nerve. HGF, CNTF, or BDNF was injected at different dosages intravitreally after injury. Ganglion cell survival was quantified at 7, 14, or 28 days postinjury. Peripheral nerve (PN) grafting to the cut optic nerve of the growth factor-injected eye was performed either immediately after injury or delayed until 7 days post-injury. Expression of heat-shock protein 27 and changes in microglia numbers were quantified in different growth factor groups. The cellular distribution of c-Met in the retina was examined by anti-c-Met immunostaining. Hepatocyte Growth Factor (HGF) was equally potent as BDNF in promoting short-term survival (up to 14 days post-injury) and also supported survival at 28 days post-injury when ganglion cells treated by CNTF or BDNF failed to be sustained. When grafting was performed without delay, HGF stimulated twice the number of axons to regenerate compared with control but was less potent than CNTF. However, in PN grafting delayed for 7 days after optic nerve injury, HGF maintained a better propensity of ganglion cells to regenerate than CNTF. Unlike CNTF, HGF application did not increase HSP27 expression in ganglion cells. Microglia proliferation was prolonged in HGF-treated retinas compared with CNTF or BDNF. C-Met was localized to both ganglion cells and Muller cells, suggesting HGF could be neuroprotective via interacting with both neurons and glia. Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to

  8. Newborn neurons in the olfactory bulb selected for long-term survival through olfactory learning are prematurely suppressed when the olfactory memory is erased.

    Science.gov (United States)

    Sultan, Sébastien; Rey, Nolwen; Sacquet, Joelle; Mandairon, Nathalie; Didier, Anne

    2011-10-19

    A role for newborn neurons in olfactory memory has been proposed based on learning-dependent modulation of olfactory bulb neurogenesis in adults. We hypothesized that if newborn neurons support memory, then they should be suppressed by memory erasure. Using an ecological approach in mice, we showed that behaviorally breaking a previously learned odor-reward association prematurely suppressed newborn neurons selected to survive during initial learning. Furthermore, intrabulbar infusions of the caspase pan-inhibitor ZVAD (benzyloxycarbonyl-Val-Ala-Asp) during the behavioral odor-reward extinction prevented newborn neurons death and erasure of the odor-reward association. Newborn neurons thus contribute to the bulbar network plasticity underlying long-term memory.

  9. Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

    Science.gov (United States)

    Sargento, Luis; Simões, Andre Vicente; Longo, Susana; Lousada, Nuno; Reis, Roberto Palma Dos

    2017-05-01

    Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P 40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P 40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

  10. Docosahexaenoic acid signaling modulates cell survival in experimental ischemic stroke penumbra and initiates long-term repair in young and aged rats.

    Directory of Open Access Journals (Sweden)

    Tiffany N Eady

    Full Text Available Docosahexaenoic acid, a major omega-3 essential fatty acid family member, improves behavioral deficit and reduces infarct volume and edema after experimental focal cerebral ischemia. We hypothesize that DHA elicits neuroprotection by inducing AKT/p70S6K phosphorylation, which in turn leads to cell survival and protects against ischemic stroke in young and aged rats.Rats underwent 2 h of middle cerebral artery occlusion (MCAo. DHA, neuroprotectin D1 (NPD1 or vehicle (saline was administered 3 h after onset of stroke. Neurological function was evaluated on days 1, 2, 3, and 7. DHA treatment improved functional recovery and reduced cortical, subcortical and total infarct volumes 7 days after stroke. DHA also reduced microglia infiltration and increased the number of astrocytes and neurons when compared to vehicle on days 1 and 7. Increases in p473 AKT and p308 AKT phosphorylation/activation were observed in animals treated with DHA 4 h after MCAo. Activation of other members of the AKT signaling pathway were also observed in DHA treated animals including increases in pS6 at 4 h and pGSK at 24 h. DHA or NPD1 remarkably reduced total and cortical infarct in aged rats. Moreover, we show that in young and aged rats DHA treatment after MCAo potentiates NPD1 biosynthesis. The phosphorylation of p308 AKT or pGSK was not different between groups in aged rats. However, pS6 expression was increased with DHA or NPD1 treatment when compared to vehicle.We suggest that DHA induces cell survival, modulates the neuroinflammatory response and triggers long term restoration of synaptic circuits. Both DHA and NPD1 elicited remarkable protection in aged animals. Accordingly, activation of DHA signaling might provide benefits in the management of ischemic stroke both acutely as well as long term to limit ensuing disabilities.

  11. KINET: a social marketing programme of treated nets and net treatment for malaria control in Tanzania, with evaluation of child health and long-term survival.

    Science.gov (United States)

    Schellenberg, J R; Abdulla, S; Minja, H; Nathan, R; Mukasa, O; Marchant, T; Mponda, H; Kikumbih, N; Lyimo, E; Manchester, T; Tanner, M; Lengeler, C

    1999-01-01

    We present a large-scale social marketing programme of insecticide-treated nets in 2 rural districts in southwestern Tanzania (population 350,000) and describe how the long-term child health and survival impact will be assessed. Formative and market research were conducted in order to understand community perceptions, knowledge, attitudes and practice with respect to the products to be socially marketed. We identified Zuia Mbu (Kiswahili for 'prevent mosquitoes') as a suitable brand name for both treated nets and single-dose insecticide treatment sachets. A mix of public and private sales outlets is used for distribution. In the first stage of a stepped introduction 31 net agents were appointed and trained in 18 villages: 15 were shop owners, 14 were village leaders, 1 was a parish priest and 1 a health worker. For net treatment 37 young people were appointed in the same villages and trained as agents. Further institutions in both districts such as hospitals, development projects and employers were also involved in distribution. Promotion for both products was intense and used a variety of channels. A total of 22,410 nets and 8072 treatments were sold during the first year: 18 months after launching, 46% of 312 families with children aged under 5 years reported that their children were sleeping under treated nets. A strong evaluation component in over 50,000 people allows assessment of the long-term effects of insecticide-treated nets on child health and survival, anaemia in pregnancy, and the costs of the intervention. This evaluation is based on cross-sectional surveys, and case-control and cohort studies.

  12. Survival and cardiovascular events after coarctation-repair in long-term follow-up (COAFU): Predictive value of clinical variables.

    Science.gov (United States)

    Bambul Heck, P; Pabst von Ohain, J; Kaemmerer, H; Ewert, P; Hager, A

    2017-02-01

    Long-term sequelae and events after coarctation repair are well described. However, the predictive value of variables from clinical follow-up investigation for late events and survival has rarely been investigated. All patients who participated in the prospective cross-sectional COALA Study in 2000 with a structural clinical investigation including blood pressure measurement and symptom-limited exercise test were contacted for reevaluation of survival, current clinical status and major cardiovascular events. Of 273 eligible patients, 209 were available for follow-up. Nine patients had died at a median age of 46years (range 30-64years), five of them due to cardiovascular complications. Late mortality after surgical intervention was 5.7% with a median age of 41years (range 16-64years). Twenty-five patients had a major cardiovascular event: 12 had procedures at the aortic valve or aortic arch, 8 had procedures for restenosis, 2 had endocarditis, 2 had a cerebrovascular insult and 1 an aortic dissection. The presence of bicuspid aortic valve (p=0.009), brachial-ankle blood pressure gradient >20mmHg (p<0.001) and reduced left ventricular function (p=0.002) correlated with major cardiovascular events. Surgical correction of coarctation of the aorta shows fairly low mortality in the long-term follow-up. Late morbidities include recoarctation, but also the consequences of the hemodynamics produced by a congenital bicuspid aortic valve, presence of which is predictive for aortic valve procedures: however the predictive value of clinical variables is limited. Copyright © 2016. Published by Elsevier Ireland Ltd.

  13. Long-Term Survival after Gamma Knife Radiosurgery in a Case of Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature

    Science.gov (United States)

    Thumma, Sudheer R.; Elaimy, Ameer L.; Daines, Nathan; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

    2012-01-01

    The management of recurrent glioblastoma is highly challenging, and treatment outcomes remain uniformly poor. Glioblastoma is a highly infiltrative tumor, and complete surgical resection of all microscopic extensions cannot be achieved at the time of initial diagnosis, and hence local recurrence is observed in most patients. Gamma Knife radiosurgery has been used to treat these tumor recurrences for select cases and has been successful in prolonging the median survival by 8–12 months on average for select cases. We present the unique case of a 63-year-old male with multiple sequential recurrences of glioblastoma after initial standard treatment with surgery followed by concomitant external beam radiation therapy and chemotherapy (temozolomide). The patient was followed clinically as well as with surveillance MRI scans at every 2-3-month intervals. The patient underwent Gamma Knife radiosurgery three times for 3 separate tumor recurrences, and the patient survived for seven years following the initial diagnosis with this aggressive treatment. The median survival in patients with recurrent glioblastoma is usually 8–12 months after recurrence, and this unique case illustrates that aggressive local therapy can lead to long-term survivors in select situations. We advocate that each patient treatment at the time of recurrence should be tailored to each clinical situation and desire for quality of life and improved longevity. PMID:22548078

  14. Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis.

    Science.gov (United States)

    Landau, H; Smith, M; Landry, C; Chou, J F; Devlin, S M; Hassoun, H; Bello, C; Giralt, S; Comenzo, R L

    2017-01-01

    Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with SCT with or without consolidation. Melphalan was administered at 100 (14%), 140 (52%) and 200 (34%) mg/m 2 . The TRM rate at 100 days was 5%. RA-SCT resulted in CR in 24% (3 months) and 48% (12 months) of patients. The CR rate was particularly high (62%) in patients offered bortezomib consolidation. With a median follow-up among survivors of 7.7 years, median event-free survival (EFS) with RA-SCT was 4.04 years (95% confidence interval (CI): 3.41-5.01 years); median OS was 10.4 years (95% CI: 7.3-not achieved). Patients with CR at 12 months after SCT had significantly longer EFS (P=0.01) and OS (P=0.04). In a multivariate analysis, melphalan dose had no impact on EFS (P=0.26) or OS (P=0.11). For selected patients, RA-SCT was safe and was associated with extended long-term survival. With the availability of novel agents for consolidation, RA-SCT remains a very effective and important backbone treatment for AL amyloidosis.

  15. Survival or revival: long-term preservation induces a reversible viable but non-culturable state in methane-oxidizing bacteria.

    Directory of Open Access Journals (Sweden)

    Sven Hoefman

    Full Text Available Knowledge on long-term preservation of micro-organisms is limited and research in the field is scarce despite its importance for microbial biodiversity and biotechnological innovation. Preservation of fastidious organisms such as methane-oxidizing bacteria (MOB has proven difficult. Most MOB do not survive lyophilization and only some can be cryopreserved successfully for short periods. A large-scale study was designed for a diverse set of MOB applying fifteen cryopreservation or lyophilization conditions. After three, six and twelve months of preservation, the viability (via live-dead flow cytometry and culturability (via most-probable number analysis and plating of the cells were assessed. All strains could be cryopreserved without a significant loss in culturability using 1% trehalose in 10-fold diluted TSB (TT as preservation medium and 5% DMSO as cryoprotectant. Several other cryopreservation and lyophilization conditions, all of which involved the use of TT medium, also allowed successful preservation but showed a considerable loss in culturability. We demonstrate here that most of these non-culturables survived preservation according to viability assessment indicating that preservation induces a viable but non-culturable (VBNC state in a significant fraction of cells. Since this state is reversible, these findings have major implications shifting the emphasis from survival to revival of cells in a preservation protocol. We showed that MOB cells could be significantly resuscitated from the VBNC state using the TT preservation medium.

  16. LONG-TERM RESULTS OF TARGET THERAPY WITH FIRST AND * SECOND-LINE TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    L. L. Vysotskaya

    2015-01-01

    Full Text Available Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib and second line (nilotinib, overall survival was 100%.Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival.

  17. Long-Term Survival According to Histology and Radiologic Response to Preoperative Chemotherapy in 126 Patients Undergoing Resection of Non-GIST Sarcoma Liver Metastases.

    Science.gov (United States)

    Goumard, Claire; Marcal, Leonardo P; Wang, Wei-Lien; Somaiah, Neeta; Okuno, Masayuki; Roland, Christina L; Tzeng, Ching-Wei D; Chun, Yun Shin; Feig, Barry W; Vauthey, Jean-Nicolas; Conrad, Claudius

    2018-01-01

    Non-gastrointestinal stromal tumor sarcomas (NGSs) have heterogeneous histology, and this heterogeneity may lead to uncertainty regarding the prognosis of patients with liver metastases from NGS (NGSLM) and decision regarding their surgical management. Furthermore, the role of preoperative chemotherapy in treatment of NGSLM remains poorly defined. We investigated long-term survival and its correlation to response to preoperative chemotherapy in patients with NGSLM. Patients who underwent liver resection for NGSLM during 1998-2015 were identified. Clinical, histopathologic, and survival data were analyzed. Multivariate analysis was performed using a Cox proportional hazards model. 126 patients [62 (49%) with leiomyosarcoma] were included. Five-year overall survival (OS) and recurrence-free survival (RFS) rates were 49.3 and 14.9%, respectively. Survival did not differ by histologic subtype, primary tumor location, or use of preoperative or postoperative chemotherapy. NGSLM ≥ 10 cm and extrahepatic metastases at NGSLM diagnosis were the only independent risk factors for OS. In the 83 (66%) patients with metachronous NSGLM, disease-free interval > 6 months was associated with improved OS and RFS. Among the 65 patients (52%) who received preoperative chemotherapy, radiologic response according to Choi criteria specifically was associated with improved OS (p = 0.04), but radiologic response according to RECIST 1.1 criteria was not. Resection of NGSLM led to a 5-year OS rate of 49%, independent of histologic subtype and primary tumor location. Choi criteria (which take into account tumor density) are superior to RECIST 1.1 in assessing radiologic response and should be used to assess response to preoperative chemotherapy.

  18. [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial.

    Science.gov (United States)

    Iten, Fabienne; Muller, Beat; Schindler, Christian; Rasch, Helmut; Rochlitz, Christoph; Oertli, Daniel; Maecke, Helmut R; Muller-Brand, Jan; Walter, Martin A

    2009-05-15

    The authors aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N'''-tetraacetic acid [(90)Y-DOTA]-Tyr(3)-octreotide (TOC) in advanced iodine-refractory thyroid cancer. In a phase 2 trial, the authors investigated biochemical response (assessed by serum thyroglobulin levels), survival, and the long-term safety profile of systemic [(90)Y-DOTA]-TOC treatment in metastasized iodine-refractory thyroid cancer. Adverse events were assessed according to the National Cancer Institute criteria. Survival analyses were performed by using multiple regression models. A total of 24 patients were enrolled. A median cumulative activity of 13.0 GBq (range, 1.7-30.3 GBq) was administered. Response was found in 7 (29.2%) patients. Eight (33.3%) patients developed hematologic toxicity grade 1-3, and 4 (16.7%) patients developed renal toxicity grade 1-4. The median survival was 33.4 months (range, 3.6-126.8 months) from time of diagnosis and 16.8 months (range, 1.8-99.1 months) from time of first [(90)Y-DOTA]-TOC treatment. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.03-0.92; P = .04) and from time of first [(90)Y-DOTA]-TOC therapy (HR, 0.20; 95% CI, 0.04-0.94; P = .04). The visual grade of scintigraphic tumor uptake was not associated with treatment response (odds ratio [OR], 0.98; 95% CI, 0.26-3.14; P = 1.00). Response to [(90)Y-DOTA]-TOC in metastasized iodine-refractory thyroid cancer was associated with longer survival. Upcoming trials should aim to increase the number of treatment cycles.

  19. Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Tao HM

    2016-03-01

    Full Text Available Hengmin Tao,1,2 Yumei Wei,1 Wei Huang,1 Xiujuan Gai,1,2 Baosheng Li11Department of 6th Radiation Oncology, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaAim: In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF have been involved in the treatment of nasopharyngeal carcinoma (NPC. However, the potential clinical effects and toxicities are still controversial.Methods: Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS, 5-year progression-free survival (PFS, 5-year locoregional recurrence-free survival (LRFS, and relevant toxicities were analyzed.Results: In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months. The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568. In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773 and 5-year LRFS (88.1% vs 90.8%, P=0.903. Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05.Conclusion: Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.Keywords: intensity

  20. The application of Gadopentate-Dimeneglumin has no impact on progression free and overall survival as well as renal function in patients with monoclonal plasma cell disorders if general precautions are taken

    Energy Technology Data Exchange (ETDEWEB)

    Hillengass, J. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany); Stoll, J.; Wagner, B.; Goldschmidt, H. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Zechmann, C.M. [Rinecker Proton Therapy Center, Munich (Germany); Kunz, C.; Heiss, C. [German Cancer Research Center Heidelberg, Department of Biostatistics, Heidelberg (Germany); Sumkauskaite, M. [University of Heidelberg, Department of Radiology, Heidelberg (Germany); Moehler, T.M. [InVentiv Health Clinical, Wiesbaden (Germany); Schlemmer, H.P.; Delorme, S. [German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany)

    2014-10-31

    The current analysis investigated the prognostic significance of gadopentetate dimeglumine on survival and renal function in patients with monoclonal plasma cell disorders. In this study 263 patients who had received gadopentetate dimeglumine within a prospective trial investigating dynamic contrast-enhanced magnetic resonance imaging (MRI) were compared with 335 patients who had undergone routine, unenhanced MRI. We found no significant prognostic impact of the application of contrast agent on progression-free survival in patients with either monoclonal gammopathy of undetermined significance, smouldering or symptomatic myeloma and no significant prognostic impact on overall survival in patients with symptomatic myeloma. Since renal impairment is a frequent complication of myeloma, and decreased renal function is associated with a higher risk of complications in patients receiving contrast agents, we evaluated the impact of contrast agent on renal function after 1 year. In the present analysis the only significant adverse impact on kidney function occurred in symptomatic myeloma patients who already had impaired renal parameters at baseline. Here, the renal function did not recover during therapy, whereas it did so in patients with normal or only slightly impaired renal function. If general recommendations are adhered to, gadopentetate dimeglumine can be safely applied in patients with monoclonal plasma cell disease. (orig.)

  1. Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models

    International Nuclear Information System (INIS)

    Mould, R F; Lederman, M; Tai, P; Wong, J K M

    2002-01-01

    Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1-2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15-53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529-50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944-1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20- 44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457-82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which

  2. The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Swallow, Elyse; Messali, Andrew; Ghate, Sameer; McDonald, Evangeline; Duchesneau, Emilie; Perez, Jose Ricardo

    2018-04-01

    When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment. To use an economic model to compare the additional cost per month of overall survival (OS) and of progression-free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for the second-line treatment of mRCC from a third-party U.S. payer perspective. The model evaluated mean OS and PFS and costs associated with drug acquisition/administration; adverse event (AE) treatment; monitoring; and postprogression (third-line treatment, monitoring, and end-of-life costs) over 1- and 2-year horizons. Efficacy, safety, and treatment duration inputs were estimated from regimens' pivotal clinical trials; for everolimus, results were weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and administration inputs were consistent with approved prescribing information and the clinical trials used to estimate efficacy and safety inputs. Cost inputs came from published literature and public data. Additional cost per additional month of OS or PFS was calculated using the ratio of the cost difference per treated patient and the corresponding difference in mean OS or PFS between everolimus and each comparator. One-way sensitivity analyses were conducted by varying efficacy and cost inputs. Compared with everolimus, cabozantinib, nivolumab, and axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS, respectively, over 1 year. Cabozantinib and nivolumab were associated with additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2 years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1

  3. EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

    Science.gov (United States)

    Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

    2014-01-01

    BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant

  4. Prehospital sodium bicarbonate use could worsen long term survival with favorable neurological recovery among patients with out-of-hospital cardiac arrest.

    Science.gov (United States)

    Kawano, Takahisa; Grunau, Brian; Scheuermeyer, Frank X; Gibo, Koichiro; Dick, William; Fordyce, Christopher B; Dorian, Paul; Stenstrom, Robert; Straight, Ronald; Christenson, Jim

    2017-10-01

    Sodium bicarbonate (SB) is widely used for resuscitation in out-of- hospital cardiac arrest (OHCA); however, its effect on long term outcomes is unclear. From 2005-2016, we prospectively conducted a province-wide population-based observational study including adult non-traumatic OHCA patients managed by paramedics. SB was administered by paramedics based on their clinical assessments. To examine the association of SB administration and survival and favorable neurological outcome to hospital discharge, defined as modified Rankin scale of 3 or less, we performed a multivariable logistic regression analysis: (1) within propensity score matched comparison groups, and; (2) within the full cohort with missing variables addressed by multiple imputation techniques. Of 15 601 OHCA patients, 13,865 were included in this study with 5165 (37.3%) managed with SB. In the SB treated group, 118 (2.3%) patients survived and 62 (1.2%) had favorable neurological outcomes to hospital discharge, compared to 1699 (19.8%) and 831 (10.6%) in the non-SB treated group, respectively. In the 1:1 propensity matched cohort including 5638 OHCA patients, SB was associated with decreased probability of outcomes (adjusted OR for survival: 0.64, 95% CI 0.45-0.91, and adjusted OR for favorable neurological outcome: 0.59, 95% CI 0.39-0.88, respectively). The association remained consistent in the multiply imputed cohort (adjusted OR 0.48, 95 CI 0.36-0.64, and adjusted OR 0.54, 95% CI 0.38-0.76, respectively). In OHCA patients, prehospital SB administration was associated with worse survival rate and neurological outcomes to hospital discharge. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice

    International Nuclear Information System (INIS)

    Kramer, M. Gabriela; Masner, Martín; Casales, Erkuden; Moreno, María; Smerdou, Cristian; Chabalgoity, José A.

    2015-01-01

    Metastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer. 2×10 8 particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×10 7 units of an aroC − Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay. SFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90 % of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not prevent establishment of distant metastasis and death of tumor-excised animals. On the other hand, LVR01 alone also showed a significant, although limited, antitumor potential, despite its ability to invade breast cancer cells and induce granulocyte recruitment. The efficacy of the combined therapy depended on the order in which both factors were administered; inasmuch the therapeutic effect was only observed when SFV-IL-12 was administered previous to LVR01, whereas administration of LVR01 before SFV-IL-12 had negligible antitumor activity. Moreover, pre-treatment with LVR01 seemed to suppress SFV-IL-12 antiangiogenic effects associated to lower IL-12 expression in this group. Re-challenged mice were unable to reject a second 4T1 tumor

  6. [Influence of pre-transplant serum level of soluble CD30 on the long-term survival rates of kidney transplant recipients and grafts].

    Science.gov (United States)

    Chen, Jiang-hua; Lü, Rong; Chen, Ying; Wu, Jian-yong; He, Qiang; Huang, Hong-feng; Qu, Li-hui

    2005-06-15

    To investigate the influence of pre-transplant sCD30 level on the long-term survival rates of kidney transplant recipients and grafts among Chinese. A retrospective cohort of 707 patients undergoing cadaver renal transplants between Dec.1998 and Aug 2003, 467 males and 240 females, aged 40 +/- 11, with their blood samples preserved was studied. The plasma levels of sCD30 were determined by ELISA. The 5-year graft survival/functional rates of the high sCD30 group were 77.7% +/- 3.5%/85.0% +/- 3.2%, significantly lower than those of the low and intermediate groups, 84.7% +/- 2.1%/98.9% +/- 1.1% and 88.1% +/- 2.9%/95.1% +/- 1.6% respectively (all P sCD30 group was 92.4% +/- 1.6%, higher than those of the low and high sCD30 groups, 84.7% +/- 3.9% and 87.1% +/- 2.7% respectively with a significant difference between the intermediate and high sCD30 groups (P = 0.032). Pre-transplant serum level of sCD30 reflects the immune status. Recipients with high sCD30 are prone to rejection while those with low sCD30 are prone to infections.

  7. Laparoscopic Complete Mesocolic Excision versus Open Complete Mesocolic Excision for Transverse Colon Cancer: Long-Term Survival Results of a Prospective Single Centre Non-Randomized Study.

    Science.gov (United States)

    Storli, Kristian Eeg; Eide, Geir Egil

    2016-01-01

    Laparoscopic complete mesocolic excision (CME) used in the treatment of transverse colon cancer has been questioned on the basis of the technical challenges. The aim of this study was to evaluate the medium- and long-term clinical and survival outcomes after laparoscopic and open CME for transverse colon cancer and to compare the 2 approaches. This study was a retrospective non-randomized study of patients with prospectively registered data on open and laparoscopic CME for transverse colon cancer tumour-node-metastasis stages I-III operated on between 2007 and 2014. This was a single-centre study in a community teaching hospital. A total of 56 patients with transverse colon cancer were included, excluding those with tumours in the colonic flexures. The outcome aims were 4-year time to recurrence (TTR) and cancer-specific survival (CSS). Morbidity was also measured. The 4-year TTR was 93.9% in the laparoscopic group and 91.3% in the open group (p = 0.71). The 4-year CSS was 97.0% in the laparoscopic group and 91.3% in the open group (p = 0.42). This was a prospective single-institution study with a small sample size. Results of the study suggest that the laparoscopic CME approach might be the preferred approach for transverse colon cancer, especially regarding its benefits in terms of short-term morbidity, length of stay and oncological outcome. © 2016 S. Karger AG, Basel.

  8. Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation.

    Science.gov (United States)

    Zhang, Qing; Deng, Yong-Lin; Liu, Chang; Huang, Li-Hong; Shang, Lei; Chen, Xin-Guo; Wang, Le-Tian; Du, Jin-Zan; Wang, Ying; Wang, Pei-Xiao; Zhang, Hui; Shen, Zhong-Yang

    2016-11-21

    To determine whether diabetes mellitus (DM) affects prognosis/recurrence after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent LT with antiviral prophylaxis. Patient data were obtained from the China Liver Transplant Registry (https://www.cltr.org/). To compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ 2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. Univariate analysis of 1631 patients who underwent LT found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after LT between the two groups were significant ( P = 0.041), but recurrence-free survival rates were not ( P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years ( P = 0.002), the presence of vascular invasion ( P = 0.096), tumors ≤ 3 cm ( P = 0.047), two to three tumor nodules ( P = 0.007), Child-Pugh grade B ( P = 0.018), and pre-LT alanine aminotransferase levels between 40 and 80 IU/L ( P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/mL ( P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM ( P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after LT. HBV-related HCC patients with DM have decreased long-term overall survival and poor LT outcomes. Prevention strategies for HCC patients with DM are recommended.

  9. Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?

    OpenAIRE

    Latimer, N.R.; White, I.R.; Abrams, K.R.; Sieburt, U.

    2017-01-01

    Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when e...

  10. Long-term outcomes for adult craniopharyngioma following radiation therapy

    International Nuclear Information System (INIS)

    Masson-Cote, Laurence; Masucci, Giuseppina Laura; Millar, Barbara-Ann; Laperriere, Normand J.; Atenafu, Eshetu G.; Cusimano, Michael; Croul, Sidney; Mason, Warren; Sahgal, Arjun; Dept. of Radiation Oncology, Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto

    2013-01-01

    Background. We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). Material and methods. Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. Results. Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age ( 2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. Conclusion. We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not

  11. Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

    Science.gov (United States)

    Lambertini, Matteo; Boni, Luca; Michelotti, Andrea; Gamucci, Teresa; Scotto, Tiziana; Gori, Stefania; Giordano, Monica; Garrone, Ornella; Levaggi, Alessia; Poggio, Francesca; Giraudi, Sara; Bighin, Claudia; Vecchio, Carlo; Sertoli, Mario Roberto; Pronzato, Paolo; Del Mastro, Lucia

    Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0

  12. Long-term survival and causes of death in patients with ST-elevation acute coronary syndrome without obstructive coronary artery disease.

    Science.gov (United States)

    Andersson, Hedvig Bille; Pedersen, Frants; Engstrøm, Thomas; Helqvist, Steffen; Jensen, Morten Kvistholm; Jørgensen, Erik; Kelbæk, Henning; Räder, Sune Bernd Emil Werner; Saunamäki, Kari; Bates, Eric; Grande, Peer; Holmvang, Lene; Clemmensen, Peter

    2018-01-07

    We aimed to study survival and causes of death in patients with ST-elevation acute coronary syndrome (STE-ACS) with and without obstructive coronary artery disease (CAD). We included 4793 consecutive patients with STE-ACS triaged for acute coronary angiography at a large cardiac invasive centre (2009-2014). Of these, 88% had obstructive CAD (stenosis ≥50%), 6% had non-obstructive CAD (stenosis 1-49%), and 5% had normal coronary arteries. Patients without obstructive CAD were younger and more often female with fewer cardiovascular risk factors. Median follow-up time was 2.6 years. Compared with patients with obstructive CAD, the short-term hazard of death (≤30 days) was lower in both patients with non-obstructive CAD [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.27-0.89, P = 0.018] and normal coronary arteries (HR 0.31, 95% CI 0.11-0.83, P = 0.021). In contrast, the long-term hazard of death (>30 days) was similar in patients with non-obstructive CAD (HR 1.15, 95% CI 0.77-1.72, P = 0.487) and higher in patients with normal coronary arteries (HR 2.44, 95% CI 1.58-3.76, P Causes of death were cardiovascular in 70% of patients with obstructive CAD, 38% with non-obstructive CAD, and 32% with normal coronary arteries. Finally, patients without obstructive CAD had lower survival compared with an age and sex matched general population. STE-ACS patients without obstructive CAD had a long-term risk of death similar to or higher than patients with obstructive CAD. Causes of death were less often cardiovascular. This suggests that STE-ACS patients without obstructive CAD warrant medical attention and close follow-up. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  13. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection.

    Science.gov (United States)

    Salvia, Roberto; Fernández-del Castillo, Carlos; Bassi, Claudio; Thayer, Sarah P; Falconi, Massimo; Mantovani, William; Pederzoli, Paolo; Warshaw, Andrew L

    2004-05-01

    To describe clinical characteristics and outcomes of a large cohort of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas affecting the main pancreatic duct. IPMNs are being diagnosed with increasing frequency. Preoperative determination of malignancy remains problematic, and reported results of long-term survival following resection are conflicting. The combined databases from the Massachusetts General Hospital and the Pancreatic Unit of the University of Verona were analyzed. To avoid confusing overlap with mucinous cystic neoplasms, only patients with tumors of the main pancreatic duct (with or without side branch involvement) were included. A total of 140 tumors consecutively resected between 1990 and 2002 were classified as either benign (adenoma and borderline tumors) or malignant (carcinoma in situ or invasive cancer) to compare their characteristics and survival. Men and women were equally affected (mean age 65 years). Seven patients (12%) had adenomas, 40 (28%) borderline tumors, 25 (18%) carcinoma in situ, and 58 (42%) invasive carcinoma. The median age of patients with benign IPMN was 6.4 years younger than those with malignant tumors (P = 0.04). The principal symptoms were abdominal pain (65%), weight loss (44%), acute pancreatitis (23%), jaundice (17%), and onset or worsening of diabetes (12%); 27% of patients were asymptomatic. Jaundice and diabetes were significantly associated with malignant tumors. Five- and 10-year cancer-specific survival for patients with noninvasive tumors was 100%, and comparable survival of the 58 patients with invasive carcinoma was 60% and 50%. Cancer is found in 60% of patients with main-duct IPMNs. Patients with malignant tumors are 6 years older than their benign counterparts and have a higher likelihood of presenting with jaundice or new onset diabetes. No patients with benign tumors or carcinoma in situ died of their disease following resection, and those with invasive cancer had a markedly better

  14. [A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

    Science.gov (United States)

    Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

    2005-12-01

    A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

  15. Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Lesuis, Sylvie L; Maurin, Herve; Borghgraef, Peter; Lucassen, Paul J; Van Leuven, Fred; Krugers, Harm J

    2016-06-28

    Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD outcome in a bigenic mouse model which progressively develops combined tau and amyloid pathology (biAT mice).Mice were subjected to either early life stress (ELS) or to 'positive' early handling (EH) postnatally (from day 2 to 9). In biAT mice, ELS significantly compromised long term survival, in contrast to EH which increased life expectancy. In 4 month old mice, ELS-reared biAT mice displayed increased hippocampal Aβ levels, while these levels were reduced in EH-reared biAT mice. No effects of ELS or EH were observed on the brain levels of APP, protein tau, or PSD-95. Dendritic morphology was moderately affected after ELS and EH in the amygdala and medial prefrontal cortex, while object recognition memory and open field performance were not affected. We conclude that despite the strong transgenic background, early life experiences significantly modulate the life expectancy of biAT mice. Parallel changes in hippocampal Aβ levels were evident, without affecting cognition of young adult biAT mice.

  16. Long-Term Survival in Patients With Synchronous, Solitary Brain Metastasis From Non-Small-Cell Lung Cancer Treated With Radiosurgery

    International Nuclear Information System (INIS)

    Flannery, Todd W.; Suntharalingam, Mohan; Regine, William F.; Chin, Lawrence S.; Krasna, Mark J.; Shehata, Michael K.; Edelman, Martin J.; Kremer, Marnie; Patchell, Roy A.; Kwok, Young

    2008-01-01

    Purpose: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). Patients and Methods: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. Results: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS ≥90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). Conclusions: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy

  17. Long-term survival, prevalence, and cure of cancer: a population-based estimation for 818 902 Italian patients and 26 cancer types

    Science.gov (United States)

    Dal Maso, L.; Guzzinati, S.; Buzzoni, C.; Capocaccia, R.; Serraino, D.; Caldarella, A.; Dei Tos, A. P.; Falcini, F.; Autelitano, M.; Masanotti, G.; Ferretti, S.; Tisano, F.; Tirelli, U.; Crocetti, E.; De Angelis, R.; Virdone, S.; Zucchetto, A.; Gigli, A.; Francisci, S.; Baili, P.; Gatta, G.; Castaing, M.; Zanetti, R.; Contiero, P.; Bidoli, E.; Vercelli, M.; Michiara, M.; Federico, M.; Senatore, G.; Pannozzo, F.; Vicentini, M.; Bulatko, A.; Pirino, D. R.; Gentilini, M.; Fusco, M.; Giacomin, A.; Fanetti, A. C.; Cusimano, R.

    2014-01-01

    Background Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking. Patients and methods Data on 818 902 Italian cancer patients diagnosed at age 15–74 years in 1985–2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds. Results The cure fractions ranged from >90% for patients aged cancers to cancers of all ages. Five- or 10-year CRS >95% were both reached in cancers of the stomach, colon–rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained 25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%. Conclusions A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective. PMID:25149707

  18. Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

    Science.gov (United States)

    Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei

    2013-01-01

    Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models. PMID:22788986

  19. Intricate Assessment and Evaluation of Effect of Bruxism on Long-term Survival and Failure of Dental Implants: A Comparative Study.

    Science.gov (United States)

    Yadav, Kajal; Nagpal, Abhishek; Agarwal, S K; Kochhar, Aarti

    2016-08-01

    affected by bruxism. Special attention is required in such patients while doing treatment planning. For the long-term clinical success and survival of dental implants in patients, special emphasis should be given on the patient's deleterious oral habits, such as bruxism as in long run, they influence the stability of dental implants.

  20. Carbon isotope variation in shrub willow (Salix spp.) ring-wood as an indicator of long-term water status, growth and survival

    International Nuclear Information System (INIS)

    Schifman, Laura A.; Stella, John C.; Volk, Timothy A.; Teece, Mark A.

    2012-01-01

    Quantifying interannual change in water status of woody plants using stable carbon isotopes provides insight on long-term plant ecophysiology and potential success in variable environments, including under-utilized agricultural land for biomass production and highly disturbed sites for phytoremediation applications. We analyzed δ 13 C values in annual ring-wood of four shrub willow varieties used for biomass production and phytoremediation at three sites in central New York State (U.S.A). We tested a cost-effective sampling method for estimating whole-shrub water status by comparing δ 13 C values of the plant’s largest stem against a composite sample of all stems. The largest stem showed 0.3‰ 13 C enrichment (range −0.7–1.1‰) compared to the whole-plant, making it a more sensitive indicator of water status than the composite sample. Growing season precipitation exerted a strong negative influence on wood tissue chemistry, with an average 0.26‰ 13 C depletion per 100 mm increase in precipitation. An average annual 0.28‰ 13 C enrichment was also observed with increased plant age; this pattern was consistent among all four willow varieties and across sites. Finally, increased 13 C enrichment in wood tissue was positively associated with plant size at the individual plant level, and associated negatively and more variably survival at the plot scale. These results have important implications for the design and management of biomass production and phytoremediation systems. Increased sensitivity of older plants suggests that longer rotations may experience growth limitations and/or lower survival in low-precipitation years, resulting in reduced yields of biomass crops and loss of effectiveness in phytoremediation applications. -- Highlights: ► A 0.26‰ 13 C depletion in wood tissue occurred per 100 mm increase in precipitation. ► There was an average 13 C enrichment with plant age and size for all varieties. ► Greater 13 C enrichment often lead to

  1. Predicting neo-adjuvant chemotherapy response and progression-free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F-18 FDG PET/CT and diffusion-weighted MR imaging.

    Science.gov (United States)

    Yoon, Hai-Jeon; Kim, Yemi; Chung, Jin; Kim, Bom Sahn

    2018-03-30

    Predicting response to neo-adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion-weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co-occurrence matrix, the voxel-alignment matrix, neighborhood intensity difference matrix, intensity size-zone matrix (ISZM), normalized gray-level co-occurrence matrix (NGLCM), neighboring gray-level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression-free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow-up period of 17.3 months, 14 patients experienced recurrence. High-intensity zone emphasis (HIZE) and high-intensity short-zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence. © 2018 Wiley Periodicals, Inc.

  2. Magnitude of the benefit of progression-free survival as a potential surrogate marker in phase 3 trials assessing targeted agents in molecularly selected patients with advanced non-small cell lung cancer: systematic review.

    Directory of Open Access Journals (Sweden)

    Katsuyuki Hotta

    Full Text Available BACKGROUND: In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC, overall survival (OS as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed. METHODS AND FINDINGS: We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an "all-comer" design. Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs (0.99 vs. 1.04, the former exhibited greater progression-free survival-hazard ratios (PFS-HR (mean, 0.40 vs. 1.01; P<0.01. A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%. The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01. An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%. CONCLUSION: The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of ∼0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial.

  3. Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2011-02-01

    Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

  4. Short-term Automated Quantification of Radiologic Changes in the Characterization of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and Prediction of Long-term Survival.

    Science.gov (United States)

    De Giacomi, Federica; Raghunath, Sushravya; Karwoski, Ronald; Bartholmai, Brian J; Moua, Teng

    2018-03-01

    Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP). Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings. IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality. Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.

  5. Severe brain atrophy after long-term survival seen in siblings with familial amyotrophic lateral sclerosis and a mutation in the optineurin gene: a case series.

    Science.gov (United States)

    Ueno, Hiroki; Kobatake, Keitaro; Matsumoto, Masayasu; Morino, Hiroyuki; Maruyama, Hirofumi; Kawakami, Hideshi

    2011-12-12

    Previous studies have shown widespread multisystem degeneration in patients with sporadic amyotrophic lateral sclerosis who develop a total locked-in state and survive under mechanical ventilation for a prolonged period of time. However, the disease progressions reported in these studies were several years after disease onset. There have been no reports of long-term follow-up with brain imaging of patients with familial amyotrophic lateral sclerosis at an advanced stage of the disease. We report the cases of siblings with amyotrophic lateral sclerosis with homozygous deletions of the exon 5 mutation of the gene encoding optineurin, in whom brain computed tomography scans were followed up for more than 20 years. The patients were a Japanese brother and sister. The elder sister was 33 years of age at the onset of disease, which began with muscle weakness of her left lower limb. Two years later she required mechanical ventilation. She became bedridden at the age of 34, and died at the age of 57. A computed tomography scan of her brain at the age of 36 revealed no abnormality. Atrophy of her brain gradually progressed. Ten years after the onset of mechanical ventilation, atrophy of her whole brain, including the cerebral cortex, brain stem and cerebellum, markedly progressed. Her younger brother was 36 years of age at the onset of disease, which presented as muscle weakness of his left upper limb. One year later, he showed dysphagia and dysarthria, and tracheostomy ventilation was performed. He became bedridden at the age of 37 and died at the age of 55. There were no abnormal intracranial findings on brain computed tomography scans obtained at the age of 37 years. At the age of 48 years, computed tomography scans showed marked brain atrophy with ventricular dilatation. Subsequently, atrophy of the whole brain rapidly progressed as in his elder sister. We conclude that a homozygous deletion-type mutation in the optineurin gene may be associated with widespread

  6. Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2

    Directory of Open Access Journals (Sweden)

    Anders Carey

    2007-09-01

    Full Text Available Abstract Background The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD-specific T cell and antibody responses. Methods Subjects with stage II (≥ 6 +LN, III, or stage IV breast cancerwith > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3, mature cultured DC (n = 3, or mature Flt3-ligand mobilized peripheral blood DC (n = 1 loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact. Results All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6–6.7 years of follow-up. Conclusion Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac

  7. Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Update of the Long-Term Survival Results of the GETUG-01 Randomized Study

    Energy Technology Data Exchange (ETDEWEB)

    Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France); Chabaud, Sylvie [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Lagrange, Jean-Leon [Department of Radiation Oncology, Centre Hospitalo-Universitaire H. Mondor, Créteil (France); Richaud, Pierre [Department of Radiation Oncology, Institut Bergognié, Bordeaux (France); Le Prise, Elisabeth [Department of Radiation Oncology, Centre Eugène Marquis, Rennes (France); Wagner, Jean-Philippe [Department of Radiation Oncology, Institut Andrée Dutreix, Dunkerque (France); Azria, David [Department of Radiation Oncology, Institut de Cancérologie de Montpellier, Montpellier (France); Beckendorf, Veronique [Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy (France); Suchaud, Jean-Philippe [Department of Radiation Oncology, Centre Hospitalier de Roanne, Roanne (France); Bernier, Valerie [Department of Radiation Oncology, Centre Oscar Lambret, Lille (France); Perol, David [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Carrie, Christian [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France)

    2016-11-15

    Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.

  8. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  9. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study.

    Science.gov (United States)

    McDonald, Craig M; Henricson, Erik K; Abresch, Richard T; Duong, Tina; Joyce, Nanette C; Hu, Fengming; Clemens, Paula R; Hoffman, Eric P; Cnaan, Avital; Gordish-Dressman, Heather

    2018-02-03

    Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy. For this prospective cohort study, we enrolled male patients aged 2-28 years with Duchenne muscular dystrophy at 20 centres in nine countries. Patients were followed up for 10 years. We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinically meaningful mobility and upper limb milestones. We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to stand from supine of 5 s or longer and 10 s or longer, and loss of stand from supine, four-stair climb, ambulation, full overhead reach, hand-to-mouth function, and hand function. Risk of death was also assessed. This study is registered with ClinicalTrials.gov, number NCT00468832. 440 patients were enrolled during two recruitment periods (2006-09 and 2012-16). Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated (log-rank p<0·0001). Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1-4·4 years and upper limb milestones by 2·8-8·0 years compared with treatment for less than 1 month. Deflazacort was associated with increased median age at loss of three milestones by 2·1-2·7 years in comparison with prednisone or prednisolone (log-rank p<0·012). 45 patients died during the 10-year follow-up. 39 (87%) of these deaths were attributable to Duchenne-related causes in patients with known duration of

  10. Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.

    Science.gov (United States)

    Song, Guohong; Wang, Xiaoli; Jia, Jun; Yuan, Yanhua; Wan, Fengling; Zhou, Xinna; Yang, Huabing; Ren, Jun; Gu, Jiezhun; Lyerly, Herbert Kim

    2013-06-01

    Suppression of cellular immunity resulting from tumorigenesis and/or therapy might promote cancer cells' growth, progression and invasion. Here, we explored whether T lymphocyte subtypes from peripheral blood of metastatic breast cancer (MBC) female patients could be used as alternative surrogate markers for cancer progress. Additionally, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and transforming growth factor-β1 were quantitated from MBC and healthy volunteers. This study included 89 female MBC patients during the post-salvage chemotherapy follow-up and 50 age- and sex-matched healthy volunteers as control. The percentages of T lymphocyte subpopulations from peripheral blood and plasma levels of cytokines were measured. Both CD8(+)CD28(-) and CD4(+)CD25(+) were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3(+) and CD8(+)CD28(+)cells were significantly lower in MBC patients (P < 0.0001, P = 0.045, respectively). MBC patients had elevated levels of immunosuppressive cytokines IL-6 and IL-10. Patients with elevated CD8(+)CD28(-) and CD4(+)CD25(+) cells showed increased levels of IL-6, and only patients with elevated CD8(+)CD28(-) had decreased interferon-γ. Univariate analysis indicated increased CD3(+)CD4(+) or CD8(+)CD28(+)correlated with prolonged progression-free survival (PFS), while elevated CD8(+)CD28(-)associated with shorten PFS. The percent of CD8(+)CD28(-) T lymphocytes is an independent predictor for PFS through multivariate analysis. This study suggests that progressive elevated levels of CD8(+)CD28(-) suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.

  11. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

    Science.gov (United States)

    Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

    2016-01-01

    In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

  12. Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival.

    Science.gov (United States)

    Kapetanakis, Nikiforos-Ioannis; Uzan, Catherine; Jimenez-Pailhes, Anne-Sophie; Gouy, Sébastien; Bentivegna, Enrica; Morice, Philippe; Caron, Olivier; Gourzones-Dmitriev, Claire; Le Teuff, Gwénaël; Busson, Pierre

    2015-11-03

    Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2-ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2-ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.

  13. Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

    Science.gov (United States)

    Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

    2018-05-01

    The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

  14. Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients.

    Science.gov (United States)

    Cui, Shaohua; Zhao, Yizhuo; Dong, Lili; Gu, Aiqin; Xiong, Liwen; Qian, Jialin; Zhang, Wei; Niu, Yanjie; Pan, Feng; Jiang, Liyan

    2016-06-01

    Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

    Science.gov (United States)

    Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R.; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B.; Niedzwiecki, Donna; Saltz, Leonard B.; Bertagnolli, Monica M.; Goldberg, Richard M.; Rabinovitch, Peter S.; Emond, Mary; Monnat, Raymond J.; Maizels, Nancy

    2014-01-01

    Purpose Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Patients and Methods Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Results Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Conclusions Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. Trial Registration ClinicalTrials.gov NCT00003835 PMID:25310185

  16. MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.

    Directory of Open Access Journals (Sweden)

    Thomas Pavelitz

    Full Text Available Colon cancers deficient in mismatch repair (MMR may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.Cancer and Leukemia Group B 89803 (Alliance randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV or irinotecan+FU/LV (IFL, with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS, and a secondary endpoint was disease-free survival (DFS. Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.Of 625 tumor cases examined, 70 (11.2% exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11. In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.ClinicalTrials.gov NCT00003835.

  17. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    International Nuclear Information System (INIS)

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

    1981-01-01

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

  18. Severe brain atrophy after long-term survival seen in siblings with familial amyotrophic lateral sclerosis and a mutation in the optineurin gene: a case series

    Directory of Open Access Journals (Sweden)

    Ueno Hiroki

    2011-12-01

    Full Text Available Abstract Introduction Previous studies have shown widespread multisystem degeneration in patients with sporadic amyotrophic lateral sclerosis who develop a total locked-in state and survive under mechanical ventilation for a prolonged period of time. However, the disease progressions reported in these studies were several years after disease onset. There have been no reports of long-term follow-up with brain imaging of patients with familial amyotrophic lateral sclerosis at an advanced stage of the disease. We report the cases of siblings with amyotrophic lateral sclerosis with homozygous deletions of the exon 5 mutation of the gene encoding optineurin, in whom brain computed tomography scans were followed up for more than 20 years. Case presentation The patients were a Japanese brother and sister. The elder sister was 33 years of age at the onset of disease, which began with muscle weakness of her left lower limb. Two years later she required mechanical ventilation. She became bedridden at the age of 34, and died at the age of 57. A computed tomography scan of her brain at the age of 36 revealed no abnormality. Atrophy of her brain gradually progressed. Ten years after the onset of mechanical ventilation, atrophy of her whole brain, including the cerebral cortex, brain stem and cerebellum, markedly progressed. Her younger brother was 36 years of age at the onset of disease, which presented as muscle weakness of his left upper limb. One year later, he showed dysphagia and dysarthria, and tracheostomy ventilation was performed. He became bedridden at the age of 37 and died at the age of 55. There were no abnormal intracranial findings on brain computed tomography scans obtained at the age of 37 years. At the age of 48 years, computed tomography scans showed marked brain atrophy with ventricular dilatation. Subsequently, atrophy of the whole brain rapidly progressed as in his elder sister. Conclusion We conclude that a homozygous deletion

  19. SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

    International Nuclear Information System (INIS)

    Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W; Latifi, K; Hoffe, S; Moros, E; Saeed, Nadia; Tan, S; Shridhar, R

    2015-01-01

    Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

  20. SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States); Latifi, K; Hoffe, S; Moros, E [Moffitt Cancer Center, Tampa, FL (United States); Saeed, Nadia [Brwon University, Providence, RI (United States); Tan, S [Huazhong University of Science & Technology, Wuhan (China); Shridhar, R [Florida Hospital, Orlando, FL (United States)

    2015-06-15

    Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

  1. Long-Term Collections

    CERN Multimedia

    Comité des collectes à long terme

    2011-01-01

    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  2. Long-term outcomes for adult craniopharyngioma following radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Masson-Cote, Laurence; Masucci, Giuseppina Laura; Millar, Barbara-Ann; Laperriere, Normand J. [Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Atenafu, Eshetu G. [Dept. of Biostatistics, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Cusimano, Michael [Dept. of Surgery, Div. of Neurosurgery, St. Michaels Hospital, Toronto (Canada); Croul, Sidney [Dept. of Pathology, Univ. of Toronto, Toronto (Canada); Mason, Warren [Dept. of Medicine, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Sahgal, Arjun [Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada), E-mail: Arjun.sahgal@rmp.uhn.on.ca; Dept. of Radiation Oncology, Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto (Canada)

    2013-01-15

    Background. We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). Material and methods. Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. Results. Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age (<53 or {>=}53) as a prognostic factor for OS (p =0.0003) and CSS (p =0.05). PFS was observed to be worse in patients with >2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. Conclusion. We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not.

  3. Understanding cancer survivors’ information needs and information-seeking behaviors for complementary and alternative medicine from short- to long-term survival: a mixed-methods study

    Directory of Open Access Journals (Sweden)

    Lou Ann Scarton

    2018-01-01

    Conclusion: Patients continue to use CAM well into long-term cancer survivorship. Finding trustworthy sources for information on CAM presents many challenges such as reliability of source, conflicting information on efficacy, and unknown interactions with conventional medications. Study participants expressed interest in an online portal to meet these needs through patient testimonials and linkage of claims to the scientific literature. Such a portal could also aid medical librarians and clinicians in locating and evaluating CAM information on behalf of patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Malzoni, Carlos Eduardo

    1996-12-31

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Malzoni, Carlos Eduardo

    1997-12-31

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

  6. Proteomic Analysis Reveals Autophagy as Pro-Survival Pathway Elicited by Long-Term Exposure with 5-Azacitidine in High-Risk Myelodysplasia.

    Science.gov (United States)

    Romano, Alessandra; Giallongo, Cesarina; La Cava, Piera; Parrinello, Nunziatina L; Chiechi, Antonella; Vetro, Calogero; Tibullo, Daniele; Di Raimondo, Francesco; Liotta, Lance A; Espina, Virginia; Palumbo, Giuseppe A

    2017-01-01

    Azacytidine (5-AZA) is the standard first-choice treatment for high-risk myelodysplasia (MDS) patients. However, the clinical outcome for those patients who interrupt treatment or whose disease failed to respond is very poor. In order to identify the cellular pathways that are modified by long-term exposure to 5-AZA, we evaluated key proteins associated with the autophagy pathway by reverse-phase microarray (RPPA). Comparing bone marrow mononucleated cells (BMMCs) obtained from 20 newly-diagnosed patients and after four 5-AZA cycles we found an increased autophagy signaling. We then evaluated ex-vivo the effect of the combination of 5-AZA with autophagy inhibitors chloroquine (CQ) and leupeptin. Since 5-AZA and CQ showed synergism due to an increase of basal autophagy after 5-AZA exposure, we adopted a sequential treatment treating BMMCs with 5 μM 5-AZA for 72 h followed by 10 μM CQ for 24 h and found increased apoptosis, associated to a reduction of G2M phase and increase in G0-G1 phase. Long-term exposure to 5-AZA induced the reduction of the autophagic marker SQSTM1/p62, reversible by CQ or leupeptin exposure. In conclusion, we identified autophagy as a compensatory pathway occurring in MDS-BM after long-term exposure to 5-AZA and we provided evidences that a sequential treatment of 5-AZA followed by CQ could improve 5-AZA efficacy, providing novel insight for tailored therapy in MDS patients progressing after 5-AZA therapy.

  7. Proteomic Analysis Reveals Autophagy as Pro-Survival Pathway Elicited by Long-Term Exposure with 5-Azacitidine in High-Risk Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Alessandra Romano

    2017-04-01

    Full Text Available Azacytidine (5-AZA is the standard first-choice treatment for high-risk myelodysplasia (MDS patients. However, the clinical outcome for those patients who interrupt treatment or whose disease failed to respond is very poor. In order to identify the cellular pathways that are modified by long-term exposure to 5-AZA, we evaluated key proteins associated with the autophagy pathway by reverse-phase microarray (RPPA. Comparing bone marrow mononucleated cells (BMMCs obtained from 20 newly-diagnosed patients and after four 5-AZA cycles we found an increased autophagy signaling. We then evaluated ex-vivo the effect of the combination of 5-AZA with autophagy inhibitors chloroquine (CQ and leupeptin. Since 5-AZA and CQ showed synergism due to an increase of basal autophagy after 5-AZA exposure, we adopted a sequential treatment treating BMMCs with 5 μM 5-AZA for 72 h followed by 10 μM CQ for 24 h and found increased apoptosis, associated to a reduction of G2M phase and increase in G0-G1 phase. Long-term exposure to 5-AZA induced the reduction of the autophagic marker SQSTM1/p62, reversible by CQ or leupeptin exposure. In conclusion, we identified autophagy as a compensatory pathway occurring in MDS-BM after long-term exposure to 5-AZA and we provided evidences that a sequential treatment of 5-AZA followed by CQ could improve 5-AZA efficacy, providing novel insight for tailored therapy in MDS patients progressing after 5-AZA therapy.

  8. Long-term survival of patients with primary oral squamous cell carcinoma. Comparison of two treatment protocols in a prospective study; 5-Jahres-Ueberlebenswahrscheinlichkeit von Patienten mit primaeren Plattenepithelkarzinomen der Mundhoehle. Vergleich von zwei Behandlungsstrategien in einer prospektiven Studie

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, P.; Bloch-Birkholz, A.; Neukam, F.W. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Mund-, Kiefer-, Gesichtschirurgie; Grabenbauer, G.; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Leher, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Medizininformatik, Biometrie und Epidemiologie; Vairaktaris, E. [Univ. of Athens Medical School (Greece). Dept. of Maxillofacial Surgery

    2007-04-15

    Background and Purpose: In recent years, different concepts for the treatment of oral squamous cell carcinomas (OSCC) have been developed; these include preoperative simultaneous neoadjuvant radiochemotherapy and one-stage surgery with tumor ablation and reconstruction. When considering long-term survival, there is substantial evidence that multimodality treatment based on a neoadjuvant radiochemotherapy is superior to adjuvant therapy concepts based on a surgical approach with postoperative irradiation. The aim of this study was to discuss the 5-year survival rate in a neoadjuvant and an adjuvant combination treatment in patients with primary OSCC. Patients and Methods: This nonrandomized longitudinal study prospectively evaluates the long-term tumor-free survival in 128 patients with oral cancer. Two groups consisting of 74 neoadjuvantly and 54 primarily surgically treated patients were formed. 99 patients suffered from stage III and IV disease according to the UICC criteria. Long-term survival was estimated according to the Kaplan-Meier assumption. Results: The neoadjuvant treatment increases the prospect of a long-term tumor-free survival. According to Kaplan-Meier assumption the estimation for a 5-year tumor-free survival in OSCC in category T1 is 83.1% in neoadjuvant, and 70.1% in adjuvant treatment, in T2 79.6% and 57.7%, in T3 68.2% and 33.2%, in T4 51.4% and 30.5%, respectively. Significance (p < 0.05) could be proven for T1 (p = 0.002), T2 (p = 0.028), and T4 (p < 0.0001) tumors. The effectiveness of the preoperative radiochemotherapy was demonstrated in the pathohistological result of tumor-free resection specimens in 28 patients of the neoadjuvant treatment group (37.8%). On the other hand, four patients died during the preoperative combination therapy. 64.8% of the patients in the adjuvant and 71.6% in the neoadjuvant treatment group survived the observation period. Conclusion: Neoadjuvant therapy is highly effective and results in a better 5-year

  9. Survival and growth of isolated pre-antral follicles from human ovarian medulla tissue during long-term 3D culture

    DEFF Research Database (Denmark)

    Yin, H L; Kristensen, S G; Jiang, H

    2016-01-01

    during long-term culture has received only little attention. STUDY DESIGN, SIZE, DURATION: Two to ten human pre-antral follicles were encapsulated together within an alginate bead and cultured with or without ovarian interstitial tissue for either 7 days or >30 days. Follicles were cultured in either 20...... interregional project ReproHigh are thanked for having funded this study; and the Key Program of Medical Science and Technology Innovation of Nanjing Military Area Command in China (14ZX06; 11Z010). They had no role in the study design, collection and analysis of data, data interpretation or in writing...

  10. Whole-Body Exposure to 28Si-Radiation Dose-Dependently Disrupts Dentate Gyrus Neurogenesis and Proliferation in the Short Term and New Neuron Survival and Contextual Fear Conditioning in the Long Term.

    Science.gov (United States)

    Whoolery, Cody W; Walker, Angela K; Richardson, Devon R; Lucero, Melanie J; Reynolds, Ryan P; Beddow, David H; Clark, K Lyles; Shih, Hung-Ying; LeBlanc, Junie A; Cole, Mara G; Amaral, Wellington Z; Mukherjee, Shibani; Zhang, Shichuan; Ahn, Francisca; Bulin, Sarah E; DeCarolis, Nathan A; Rivera, Phillip D; Chen, Benjamin P C; Yun, Sanghee; Eisch, Amelia J

    2017-11-01

    Astronauts traveling to Mars will be exposed to chronic low doses of galactic cosmic space radiation, which contains highly charged, high-energy (HZE) particles. 56 Fe-HZE-particle exposure decreases hippocampal dentate gyrus (DG) neurogenesis and disrupts hippocampal function in young adult rodents, raising the possibility of impaired astronaut cognition and risk of mission failure. However, far less is known about how exposure to other HZE particles, such as 28 Si, influences hippocampal neurogenesis and function. To compare the influence of 28 Si exposure on indices of neurogenesis and hippocampal function with previous studies on 56 Fe exposure, 9-week-old C57BL/6J and Nestin-GFP mice (NGFP; made and maintained for 10 or more generations on a C57BL/6J background) received whole-body 28 Si-particle-radiation exposure (0, 0.2 and 1 Gy, 300 MeV/n, LET 67 KeV/μ, dose rate 1 Gy/min). For neurogenesis assessment, the NGFP mice were injected with the mitotic marker BrdU at 22 h postirradiation and brains were examined for indices of hippocampal proliferation and neurogenesis, including Ki67 + , BrdU + , BrdU + NeuN + and DCX + cell numbers at short- and long-term time points (24 h and 3 months postirradiation, respectively). In the short-term group, stereology revealed fewer Ki67 + , BrdU + and DCX + cells in 1-Gy-irradiated group relative to nonirradiated control mice, fewer Ki67 + and DCX + cells in 0.2 Gy group relative to control group and fewer BrdU + and DCX + cells in 1 Gy group relative to 0.2 Gy group. In contrast to the clearly observed radiation-induced, dose-dependent reductions in the short-term group across all markers, only a few neurogenesis indices were changed in the long-term irradiated groups. Notably, there were fewer surviving BrdU + cells in the 1 Gy group relative to 0- and 0.2-Gy-irradiated mice in the long-term group. When the short- and long-term groups were analyzed by sex, exposure to radiation had a similar effect on neurogenesis indices

  11. Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial

    International Nuclear Information System (INIS)

    Eltabbakh, Gamal H.; Piver, M. Steven; Hempling, Ronald E.; Shin, Kyu H.

    1997-01-01

    Purpose: The value of adjuvant radiation therapy and staging pelvic lymphadenectomy in patients with low-risk, early-stage endometrial cancer is controversial. The aim of this study was to report the long-term survival, rate of recurrences, and complications in patients with Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion treated with hysterectomy (without formal staging pelvic and periaortic lymph node sampling or lymph-adenectomy) and postoperative vaginal brachytherapy. Methods and Materials: A total of 303 patients with pathologic Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion and nonmalignant peritoneal cytology, were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal brachytherapy (30 Gy to point 0.5 cm depth) in a prospective study extending from 1958 to 1994. In addition, 29 additional Stage I, Grade 1-2 patients with <50% myometrial invasion and malignant peritoneal cytology were treated with 1 year of progesterone therapy. Patients were followed for 1.2-32 years (median 8.1 y). Results: Six patients had recurrences and died secondary to disease. There were no vaginal recurrences. The 5-, 10-, 20-, and 30-year disease-free survivals of the 303 patients with nonmalignant peritoneal cytology were 98.9%, 97.8%, 96.7%, and 96.7%, respectively. Patients with malignant peritoneal cytology had a 5- and 10-year disease-free survival of 100%. Significant radiation complications occurred in 2.1% of the patients. Conclusion: In patients with low-risk, Stage I endometrial cancer, hysterectomy and adjuvant postoperative vaginal brachytherapy provide excellent long-term survival, eliminate vaginal recurrences, and are not associated with significant complications. The addition of 1 year of progesterone therapy to patients with malignant cytology provides 100% long-term survival. Based on these results, patients with low-risk, Stage I endometrial adenocarcinoma do not need

  12. Long-term follow-up of patients receiving allogeneic stem cell transplant for chronic lymphocytic leukaemia: mixed T-cell chimerism is associated with high relapse risk and inferior survival.

    Science.gov (United States)

    Thompson, Philip A; Stingo, Francesco; Keating, Michael J; Wierda, William G; O'Brien, Susan M; Estrov, Zeev; Ledesma, Celina; Rezvani, Katayoun; Qazilbash, Muzaffar; Shah, Nina; Parmar, Simrit; Popat, Uday; Anderlini, Paolo; Yago, Nieto; Ciurea, Stefan O; Kebriaei, Partow; Champlin, Richard; Shpall, Elizabeth J; Hosing, Chitra M

    2017-05-01

    There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P CLL. © 2017 John Wiley & Sons Ltd.

  13. Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy

    International Nuclear Information System (INIS)

    Bianco, Fernando J.; Scardino, Peter T.; Stephenson, Andrew J.; DiBlasio, Christopher J.; Fearn, Paul A.; Eastham, James A.

    2005-01-01

    Purpose: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. Methods and Materials: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of ≥0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). Results: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of 10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. Conclusions: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent

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

    Science.gov (United States)

    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

  15. Can resistant coral-Symbiodinium associations enable coral communities to survive climate change? A study of a site exposed to long-term hot water input

    Directory of Open Access Journals (Sweden)

    Shashank Keshavmurthy

    2014-04-01

    Full Text Available Climate change has led to a decline in the health of corals and coral reefs around the world. Studies have shown that, while some corals can cope with natural and anthropogenic stressors either through resistance mechanisms of coral hosts or through sustainable relationships with Symbiodinium clades or types, many coral species cannot. Here, we show that the corals present in a reef in southern Taiwan, and exposed to long-term elevated seawater temperatures due to the presence of a nuclear power plant outlet (NPP OL, are unique in terms of species and associated Symbiodinium types. At shallow depths (<3 m, eleven coral genera elsewhere in Kenting predominantly found with Symbiodinium types C1 and C3 (stress sensitive were instead hosting Symbiodinium type D1a (stress tolerant or a mixture of Symbiodinium type C1/C3/C21a/C15 and Symbiodinium type D1a. Of the 16 coral genera that dominate the local reefs, two that are apparently unable to associate with Symbiodinium type D1a are not present at NPP OL at depths of <3 m. Two other genera present at NPP OL and other locations host a specific type of Symbiodinium type C15. These data imply that coral assemblages may have the capacity to maintain their presence at the generic level against long-term disturbances such as elevated seawater temperatures by acclimatization through successful association with a stress-tolerant Symbiodinium over time. However, at the community level it comes at the cost of some coral genera being lost, suggesting that species unable to associate with a stress-tolerant Symbiodinium are likely to become extinct locally and unfavorable shifts in coral communities are likely to occur under the impact of climate change.

  16. Major clinical events, signs and severity assessment scores related to actual survival in patients who died from primary biliary cirrhosis. A long-term historical cohort study

    NARCIS (Netherlands)

    van Dam, GM; Gips, CH; Reisman, Y; Maas, KW; Purmer, IM; Huizenga, [No Value; Verbaan, BW

    1999-01-01

    BACKGROUND/AIMS: One of the prognostic methods for survival in primary biliary cirrhosis (PBC) is the Mayo model, with a time-scale limited to 7 years. The aim of our study was to assess how major clinical events, signs, several severity assessment methods and Mayo survival probabilities fit in with

  17. Long-Term Collections

    CERN Multimedia

    Staff Association

    2016-01-01

    45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

  18. Long-Term Collection

    CERN Multimedia

    Staff Association

    2016-01-01

    Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

  19. Collectes à long terme

    CERN Multimedia

    Collectes à long terme

    2014-01-01

    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  20. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  1. Multi-Trial Evaluation of Progression-Free Survival (PFS) as a Surrogate Endpoint for Overall Survival (OS) in First-Line Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

    Science.gov (United States)

    Foster, Nathan R.; Renfro, Lindsay A.; Schild, Steven E.; Redman, Mary W.; Wang, Xiaofei F.; Dahlberg, Suzanne E.; Ding, Keyue; Bradbury, Penelope A.; Ramalingam, Suresh S.; Gandara, David R.; Shibata, Taro; Saijo, Nagahiro; Vokes, Everett E.; Adjei, Alex A.; Mandrekar, Sumithra J.

    2015-01-01

    Introduction We previously reported that PFS may be a candidate surrogate endpoint for OS in first-line ES-SCLC using data from 3 randomized trials (Foster, Cancer 2011). In this validation study (N0424-Alliance), we assessed the patient- and trial-level surrogacy of PFS using data from 7 new first-line phase II/III ES-SCLC trials and across all 10 trials as well (7 new, 3 previous). Methods Individual patient data were utilized across the 7 new trials (2259 patients) and all 10 trials (2855 patients). Patient-level surrogacy (Kendall’s τ) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed via association of the log hazard ratios on OS and PFS across trials, including weighted (by trial size) least squares regression of Cox model effects (WLS R2) and correlation of the copula effects (Copula R2). The minimum effect on the surrogate (MES) needed to detect a non-zero treatment effect on OS was also calculated. Results The median OS and PFS across all 10 trials were 9.8 and 5.9 months, respectively. PFS showed strong surrogacy within the 7 new trials (Copula R2 = 0.90 (SE=0.27); WLS R2 = 0.83 (95% CI: 0.43, 0.95); MES=0.67; Kendall’s τ = 0.58) and across all 10 trials (Copula R2 =0.81 (SE=0.25); WLS R2=0.77 (95% CI: 0.47–0.91); MES=0.70; Kendall’s τ =0.57). Conclusions PFS demonstrated strong surrogacy for OS in first-line ES-SCLC based on this external validation study of individual patient data. PFS is a good alternative endpoint to OS and should be considered when resource constraints (time or patient) might make it useful or desirable in place of OS. Additional analyses are needed to assess its appropriateness for targeted agents in this disease setting. PMID:26134227

  2. Long-term results of radiation combined with cisplatin in localized muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Hara, Takahiro; Nishijima, Jun; Miyachika, Yoshihiro; Yamamoto, Yoshiaki; Nagao, Kazuhiro; Sakano, Shigeru; Matsuyama, Hideyasu; Naito, Katsusuke

    2011-01-01

    Although radical cystectomy is the standard treatment for localized muscle invasive-bladder cancer, bladder preservation therapies have been tried for selective patients in several institutes. However, the indication of bladder preservation therapy remains controversial. To select patients who are good candidates for bladder preservation therapy, we evaluated our long-term experience with radiation therapy (conformal radiotherapy (CRT)) combined with cisplatin. Between 1994 and 2009, 90 patients with bladder cancer (clinical stage T2-4N0M0) with no evidence of upper urinary tract cancer were treated with CRT. The response was evaluated by transurethral resection (TUR) of the tumor, urine cytology and CT scan. Thirty-seven cases (41.1%) achieved pathological complete response (CR) which was defined as no microscopic residual tumor in the bladder. After TUR, 74 cases (82.2%) achieved local control of the cancer that was considered as clinical CR. Among 16 patients for whom clinical CR was not achieved, 8 cases were treated with immediate radical cystectomy. We evaluated the long-term results of CRT in 82 cases with bladder preservation. The median follow-up was 36.6 months (range, 4.1-155.1). The five-year overall survival rate and the 5-year progression-free survival rate were 73.0% and 59.2%, respectively. Clinical T stage and type of tumor (primary or recurrent) were prognostic factors for overall survival (p=0.003 and p=0.017). Likewise, clinical T stage and type of tumor were prognostic factors for progression-free survival (p=0.022 and p=0.033). In addition, primary cT2 cases had a significantly better prognosis than those with other T stage and recurrence in overall survival and progression-free survival (p=0.007 and p=0.018). Based on these data, we concluded that primary cT2 tumors were good candidates for radiation combined with cisplatin for bladder preservation therapy. (author)

  3. CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Daniel Gómez-Cabello

    2017-02-01

    Full Text Available Acquired genomic instability is one of the major concerns for the clinical use of induced pluripotent stem cells (iPSCs. All reprogramming methods are accompanied by the induction of DNA damage, of which double-strand breaks are the most cytotoxic and mutagenic. Consequently, DNA repair genes seem to be relevant for accurate reprogramming to minimize the impact of such DNA damage. Here, we reveal that reprogramming is associated with high levels of DNA end resection, a critical step in homologous recombination. Moreover, the resection factor CtIP is essential for cell reprogramming and establishment of iPSCs, probably to repair reprogramming-induced DNA damage. Our data reveal a new role for DNA end resection in maintaining genomic stability during cell reprogramming, allowing DNA repair fidelity to be retained in both human and mouse iPSCs. Moreover, we demonstrate that reprogramming in a resection-defective environment has long-term consequences on stem cell self-renewal and differentiation.

  4. Long-term survival benefit of revascularization compared with medical therapy in patients with coronary chronic total occlusion and well-developed collateral circulation.

    Science.gov (United States)

    Jang, Woo Jin; Yang, Jeong Hoon; Choi, Seung-Hyuk; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Kim, Wook Sung; Lee, Young Tak; Gwon, Hyeon-Cheol

    2015-02-01

    The purpose of this study was to compare the long-term clinical outcomes of patients with chronic total occlusion (CTO) and well-developed collateral circulation treated with revascularization versus medical therapy. Little is known about the clinical outcomes and optimal treatment strategies of CTO with well-developed collateral circulation. We screened 2,024 consecutive patients with at least 1 CTO detected on coronary angiogram. Of these, we analyzed data from 738 patients with Rentrop 3 grade collateral circulation who were treated with medical therapy alone (n = 236), coronary artery bypass grafting (n = 170) or percutaneous coronary intervention (n = 332; 80.1% successful). Patients who underwent revascularization and medical therapy (revascularization group, n = 502) were compared with those who underwent medical therapy alone (medication group, n = 236) in terms of cardiac death and major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, and repeat revascularization. During a median follow-up duration of 42 months, multivariate analysis revealed a significantly lower incidence of cardiac death (hazard ratio [HR]: 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p collateral circulation, aggressive revascularization may reduce the risk of cardiac mortality and MACE. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.

    Science.gov (United States)

    Chen, Hongliang; Wu, Kejin; Wang, Maoli; Wang, Fuwen; Zhang, Mingdi; Zhang, Peng

    2017-12-01

    There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers.

    Science.gov (United States)

    Imhof, Anna; Brunner, Philippe; Marincek, Nicolas; Briel, Matthias; Schindler, Christian; Rasch, Helmut; Mäcke, Helmut R; Rochlitz, Christoph; Müller-Brand, Jan; Walter, Martin A

    2011-06-10

    To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers. In a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [(90)Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [(90)Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity. Overall, 1,109 patients received 2,472 cycles of [(90)Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.

  7. Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol

    International Nuclear Information System (INIS)

    Sedlacek, Scot M; Playdon, Mary C; Wolfe, Pamela; McGinley, John N; Wisthoff, Mark R; Daeninck, Elizabeth A; Jiang, Weiqin; Zhu, Zongjian; Thompson, Henry J

    2011-01-01

    Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction. Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m 2 ) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin. While clinical data indicate that excess weight for height is associated with poor prognosis for long term

  8. Industrial Foundations as Long-Term Owners

    DEFF Research Database (Denmark)

    Thomsen, Steen; Poulsen, Thomas; Børsting, Christa Winther

    Short-termism has become a serious concern for corporate governance, and this has inspired a search for institutional arrangements to promote long-term decision-making. In this paper, we call attention to long-term ownership by industrial foundations, which is common in Northern Europe but little...... known in the rest of the world. We use a unique Danish data set to document that industrial foundations are long-term owners that practice long-term governance. We show that foundation ownership is highly stable compared to other ownership structures. Foundation-owned companies replace managers less...... frequently. They have conservative capital structures with low financial leverage. They score higher on an index of long-termism in finance, investment, and employment. They survive longer. Overall, our paper supports the hypothesis that corporate time horizons are influenced by ownership structures...

  9. Long-Term Results of Radiochemotherapy for Solitary Lymph Node Metastasis After Curative Resection of Esophageal Cancer

    International Nuclear Information System (INIS)

    Jingu, Keiichi; Ariga, Hisanori; Nemoto, Kenji; Narazaki, Kakutaro; Umezawa, Rei; Takeda, Ken; Koto, Masashi; Sugawara, Toshiyuki; Kubozono, Masaki; Miyata, Go; Onodera, Ko; Yamada, Shogo

    2012-01-01

    Purpose: To evaluate the long-term efficacy and toxicity of definitive radiochemotherapy for solitary lymph node metastasis after curative surgery of esophageal cancer. Methods and Materials: We performed a retrospective review of 35 patients who underwent definitive radiochemotherapy at Tohoku University Hospital between 2000 and 2009 for solitary lymph node metastasis after curative esophagectomy with lymph node dissection for esophageal cancer. Radiotherapy doses ranged from 60 to 66 Gy (median, 60 Gy). Concurrent chemotherapy was platinum based in all patients. The endpoints of the present study were overall survival, cause-specific survival, progression-free survival, irradiated-field control, overall tumor response, and prognostic factors. Results: The median observation period for survivors was 70.0 months. The 5-year overall survival was 39.2% (median survival, 39.0 months). The 5-year cause-specific survival, progression-free survival, and irradiated-field control were 43.3%, 31.0% and 59.9%, respectively. Metastatic lesion, size of the metastatic lymph node, and performance status before radiochemotherapy were significantly correlated with prognosis. Complete response and partial response were observed in 22.9% and 57.1% of the patients, respectively. There was no Grade 3 or higher adverse effect based on theCommon Terminology Criteria for Adverse Events (CTCAE v3.0) in the late phase. Conclusions: Based on our study findings, approximately 40% of patients with solitary lymph node metastasis after curative resection for esophageal cancer have a chance of long-term survival with definitive radiochemotherapy.

  10. Radiotoxicity of systemically administered 211At-labeled human/mouse chimeric monoclonal antibody: a long-term survival study with histologic analysis

    International Nuclear Information System (INIS)

    McLendon, Roger E.; Archer, Gary E.; Larsen, Roy H.; Akabani, Gamal; Bigner, Darell D.; Zalutsky, Michael R.

    1999-01-01

    Purpose: The antitenascin human/mouse chimeric monoclonal antibody labeled with the α-particle-emitting radionuclide 211 At is of interest as an endo radiotherapeutic agent for the treatment of brain tumors. To facilitate the investigation of 211 At-labeled chimeric 81C6 in patients, the long-term radiotoxicity of this radiopharmaceutical has been evaluated. Methods and Materials: Antibody labeling was performed using N-succinimidyl 3-[ 211 At]astato-benzoate. After an initial dose-finding experiment, a second toxicity study was carried out at 4 dose levels in groups of 30 non thyroid blocked B6C3F 1 mice per group (15 males, 15 females). Male mice received either saline or 15-81 kBq/g and females received either saline or 16-83 kBq/g of 211 At-labeled antibody. Ten animals (5 males, 5 females) were followed for 6 months and the remainder for 1 year. Results: The lethal dose in 10% of animals (LD 10 ) for 211 At-labeled chimeric 81C6 was 46 kBq/g in females and 102 kBq/g in males. Toxic effects--perivascular fibrosis of the intraventricular septum of the heart, bone marrow suppression, splenic white pulp atrophy, and spermatic maturational delay--generally were confined to a few animals receiving the highest doses of labeled antibody. Conclusions: The LD 10 of 211 At-labeled chimeric 81C6 in this mouse strain was about half that of [ 211 At]astatide. These results establish the preclinical maximum tolerated dose of 211 At-labeled chimeric 81C6 and define in the mouse the target organs for toxicity. These studies will be useful for determining starting doses for clinical studies with 211 At-labeled chimeric 81C6

  11. Effect of preinfarction angina pectoris on long-term survival in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.

    Science.gov (United States)

    Taniguchi, Tomohiko; Shiomi, Hiroki; Toyota, Toshiaki; Morimoto, Takeshi; Akao, Masaharu; Nakatsuma, Kenji; Ono, Koh; Makiyama, Takeru; Shizuta, Satoshi; Furukawa, Yutaka; Nakagawa, Yoshihisa; Ando, Kenji; Kadota, Kazushige; Horie, Minoru; Kimura, Takeshi

    2014-10-15

    The influence of preinfarction angina pectoris (AP) on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) remains controversial. In 5,429 patients with acute myocardial infarction (AMI) enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto AMI Registry, the present study population consisted of 3,476 patients with STEMI who underwent primary PCI within 24 hours of symptom onset and in whom the data on preinfarction AP were available. Preinfarction AP defined as AP occurring within 48 hours of hospital arrival was present in 675 patients (19.4%). Patients with preinfarction AP was younger and more often had anterior AMI and longer total ischemic time, whereas they less often had history of heart failure, atrial fibrillation, and shock presentation. The infarct size estimated by peak creatinine phosphokinase was significantly smaller in patients with than in patients without preinfarction AP (median [interquartile range] 2,141 [965 to 3,867] IU/L vs 2,462 [1,257 to 4,495] IU/L, p <0.001). The cumulative 5-year incidence of death was significantly lower in patients with preinfarction AP (12.4% vs 20.7%, p <0.001) with median follow-up interval of 1,845 days. After adjusting for confounders, preinfarction AP was independently associated with a lower risk for death (hazard ratio 0.69, 95% confidence interval 0.54 to 0.86, p = 0.001). The lower risk for 5-year mortality in patients with preinfarction AP was consistently observed across subgroups stratified by total ischemic time, initial Thrombolysis In Myocardial Infarction flow grade, hemodynamic status, infarct location, and diabetes mellitus. In conclusion, preinfarction AP was independently associated with lower 5-year mortality in patients with STEMI who underwent primary PCI. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Introduction: Long term prediction

    International Nuclear Information System (INIS)

    Beranger, G.

    2003-01-01

    Making a decision upon the right choice of a material appropriate to a given application should be based on taking into account several parameters as follows: cost, standards, regulations, safety, recycling, chemical properties, supplying, transformation, forming, assembly, mechanical and physical properties as well as the behaviour in practical conditions. Data taken from a private communication (J.H.Davidson) are reproduced presenting the life time range of materials from a couple of minutes to half a million hours corresponding to applications from missile technology up to high-temperature nuclear reactors or steam turbines. In the case of deep storage of nuclear waste the time required is completely different from these values since we have to ensure the integrity of the storage system for several thousand years. The vitrified nuclear wastes should be stored in metallic canisters made of iron and carbon steels, stainless steels, copper and copper alloys, nickel alloys or titanium alloys. Some of these materials are passivating metals, i.e. they develop a thin protective film, 2 or 3 nm thick - the so-called passive films. These films prevent general corrosion of the metal in a large range of chemical condition of the environment. In some specific condition, localized corrosion such as the phenomenon of pitting, occurs. Consequently, it is absolutely necessary to determine these chemical condition and their stability in time to understand the behavior of a given material. In other words the corrosion system is constituted by the complex material/surface/medium. For high level nuclear wastes the main features for resolving problem are concerned with: geological disposal; deep storage in clay; waste metallic canister; backfill mixture (clay-gypsum) or concrete; long term behavior; data needed for modelling and for predicting; choice of appropriate solution among several metallic candidates. The analysis of the complex material/surface/medium is of great importance

  13. Long-Term Symbolic Learning

    National Research Council Canada - National Science Library

    Kennedy, William G; Trafton, J. G

    2007-01-01

    What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

  14. Long-Term Survival of Dental Implants with Different Prosthetic Loading Times in Healthy Patients: A 5-Year Retrospective Clinical Study.

    Science.gov (United States)

    Muelas-Jiménez, M Isabel; Olmedo-Gaya, Maria Victoria; Manzano-Moreno, Francisco J; Reyes-Botella, Candela; Vallecillo-Capilla, Manuel

    2017-02-01

    To compare survival rates among dental implants restored with immediate, early, and conventional loading protocols, also comparing between maxillary and mandibular implants, and to evaluate the influence of implant length and diameter and the type of prosthesis on treatment outcomes. This retrospective cohort study initially included all 52 patients receiving dental implants between July 2006 and February 2008 at a private oral surgery clinic in Granada (Southern Spain). Clinical and radiographic examinations were performed, including periapical or panoramic radiographs, and incidences during completion of the restoration were recorded at 1 week, 3 months, 6 months, and at 1, 2, 3, 4, and 5 years. After a 5-year follow-up, 1 patient had died, 3 were lost to follow-up, and 6 required grafting before implant placement; therefore, the final study sample comprised 42 patients with 164 implants. Variables associated with the survival/failure of the restoration were: number of implants (higher failure rate with fewer implants), bone type (higher failure rate in type III or IV bone), and type of prosthesis (higher failure rate with single crowns). No significant association was found in univariate or multivariate analyses between survival rate and the loading protocol, implant length or diameter, or maxillary/mandibular location. Immediate occlusal loading, immediate provisionalization without occlusal loading, and early loading are viable treatment options with similar survival rates to those obtained with conventional loading. Bone quality and number of implants per patient were the most influential factors. © 2015 by the American College of Prosthodontists.

  15. Clinical characteristics of long-term survival with non-invasive ventilation and factors affecting the transition to invasive ventilation in ALS.

    Science.gov (United States)

    Hirose, Takahiko; Kimura, Fumiharu; Tani, Hiroki; Ota, Shin; Tsukahara, Akihiro; Sano, Eri; Shigekiyo, Taro; Nakamura, Yoshitsugu; Kakiuchi, Kensuke; Motoki, Mikiko; Unoda, Kiichi; Ishida, Simon; Nakajima, Hideto; Arawaka, Shigeki

    2018-04-20

    Introduction We evaluated post non-invasive ventilation survival and factors for the transition to tracheostomy in amyotrophic lateral sclerosis. Methods We analyzed 197 patients using a prospectively-collected database, with 114 patients since 2000. Results Of 114 patients, 59 patients underwent non-invasive ventilation (NIV), which prolonged the total median survival time to 43 months compared with 32 months without treatment. The best post-NIV survival was associated with a lack of bulbar symptoms, higher measured pulmonary function, and a slower rate of progression at diagnosis. The transition rate from NIV to tracheostomy gradually decreased over the years. Patients using NIV for more than 6 months were more likely to refuse tracheostomy and to be female. Discussion This study confirmed a positive survival effect with NIV, which was less effective in patients with bulbar dysfunction. Further studies are necessary to determine the best timing for using NIV with ALS in patients with bulbar dysfunction. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  16. Influence of age on the prognostic importance of left ventricular dysfunction and congestive heart failure on long-term survival after acute myocardial infarction. TRACE Study Group

    DEFF Research Database (Denmark)

    Køber, L; Torp-Pedersen, C; Ottesen, M

    1996-01-01

    for entry into the TRAndolapril Cardiac Evaluation (TRACE) study. Medical history, echocardiographic estimation of LV systolic function determined as wall motion index, infarct complications, and survival were documented for all patients. To study the importance of congestive heart failure and wall motion...... dysfunction was more pronounced in the elderly than in the young....

  17. Long-term survival of subcutaneous anti-tumor necrosis factor biological drugs administered between 2008 and 2012 in a cohort of rheumatoid arthritis patients.

    Science.gov (United States)

    Alvarez Rivas, Noelia; Vazquez Rodriguez, Tomas R; Miranda Filloy, Jose A; Garcia-Porrua, Carlos; Sanchez-Andrade Fernández, Amalia

    2017-05-25

    To compare the survival of subcutaneous anti-tumor necrosis factor (TNF) drugs used between 2008 and 2012 prescribed in accordance with clinical practice. Retrospective, observational study of the patients in our center diagnosed with rheumatoid arthritis (RA). We included patients who had received a subcutaneous anti-TNF agent for at least 6 months. The data were analyzed using the SPSS V17.0 statistical package. Forty-nine RA patients started subcutaneous biological treatment with an anti-TNF agent (32 with etanercept and 17 with adalimumab). The mean age was 45.94 years (75.5% female). The mean disease duration prior to starting anti-TNF administration was 2.67 years. The mean age at the start of treatment was 51.84 years, and the average Disease Activity Score 28 was 4.93. The median survival of the anti-TNF treatment was 8.40 years; the survival of etanercept was the longer of the two. The main reason for discontinuation was secondary failure (90.9%). In routine clinical practice, the survival of subcutaneous anti-TNF treatment was extensive and was independent of whether or not the patients received concomitant immunosuppressive therapy. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  18. Early post-transplant immune monitoring can predict long-term kidney graft survival: soluble CD30 levels, anti-HLA antibodies and IgA-anti-Fab autoantibodies.

    Science.gov (United States)

    Amirzargar, Mohammad Ali; Amirzargar, Aliakbar; Basiri, Abbas; Hajilooi, Mehrdad; Roshanaei, Ghodratollah; Rajabi, Gholamreza; Mohammadiazar, Sina; Solgi, Ghasem

    2014-01-01

    This study aimed to investigate the predictive power of anti-HLA antibodies, sCD30 levels and IgA-anti-Fab autoantibody before and early after transplantation in relation to long-term kidney allograft survival. Pre- and post-transplant sera samples of 59 living-unrelated donor kidney recipients were tested for above risk factors by enzyme-linked immunoabsorbent assay. 15 out of 59 cases experienced rejection episodes (failure group). Pre- and post-transplant high sCD30 levels were significantly associated with graft failure (P=0.02 and P=0.004) and decreased 4 year graft survival (P = 0.009 and P = 0.001). Higher frequency of post-transplant HLA class-II antibody in the absence of class-I antibody was observed in failure group (P=0.007). Patients with post-transplant HLA class-I and class-II antibodies either alone or in combination showed significant lower 4 year graft survival. Recipients with high sCD30 levels in the presence of HLA class-I or class-II antibodies within 2 weeks post-transplant had poor graft survival (P = 0.004 and P = 0.002, respectively). High levels of post-transplant IgA-anti-Fab antibody was more frequent in functioning-graft patients (P = 0.00001), correlated with decreased serum creatinine levels (P = 0.01) and associated with improved graft survival (P = 0.008). Our findings indicate the deleterious effect of early post-transplant HLA antibodies and increased sCD30 levels dependently and protective effect of IgA-anti-Fab antibodies on long-term renal graft outcomes. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  19. LONG TERM COLLECTIONS