bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nomogram Predicting 10-Year Life Expectancy in Candidates for Radical Prostatectomy or Radiotherapy for Prostate Cancer
Authors: Walz Jochen , Gallina Andrea , Saad Fred , Montorsi Francesco , Perrotte Paul , Shariat Shahrokh F. , Jeldres Claudio , Graefen Markus , Bénard Francois , McCormack Michael , Valiquette Luc , Karakiewicz Pierre I. 
Published: August 2007

Purpose Candidates for definitive therapy for localized prostate cancer (PCa) should have life expectancy (LE) in excess of 10 years. However, LE estimation is difficult. To circumvent this problem, we developed a nomogram predicting 10-year LE for patients treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and compared it with an existing tool. Patients and Methods Between 1989 and 2000, 9,131 men were treated with either RP (n = 5,955) or EBRT (n = 3,176), without any secondary therapy and all deaths were considered unrelated to PCa. Age and Charlson comorbidity index (CCI) predicted 10-year LE in Cox regression models. We used 200 bootstrap resamples to internally validate the nomogram. Results Median age was 66 years, median CCI was 1, median follow-up was 5.9 years and median actuarial survival was 13.8 years. Advanced age (P < .001), elevated CCI score (P < .001) and treatment type (EBRT v RP, P < .001) were independent predictors of poor 10 year LE. The nomogram predicting 10 year LE after either RP or EBRT was 84.3% accurate in split sample validation and was 2.9% (P = .007) more accurate than the existing tool. A cutoff of 70% or less was 84% accurate in identifying men who did not survive beyond 10 years. Conclusion Our nomogram can accurately identify those individuals who do not have sufficient LE to warrant definitive PCa treatment and can help optimizing therapy decision-making.
Long-Term Results of RTOG Trial 8911 (USA Intergroup 113): A Random Assignment Trial Comparison of Chemotherapy Followed by Surgery Compared With Surgery Alone for Esophageal Cancer
Authors: Kelsen David P. , Winter Katryn A. , Gunderson Leonard L. , Mortimer Joanne , Estes Norman C. , Haller Daniel G. , Ajani Jaffer A. , Kocha Walter , Minsky Bruce D. , Roth Jack A. , Willett Christopher G. 
Published: August 2007

Purpose We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed. Patients and Methods The chemotherapy group received preoperative cisplatin plus fluorouracil. Outcome based on the type of resection (R0, R1, R2, or no resection) was evaluated. The main end point was overall survival. Disease-free survival, relapse pattern, the influence of postoperative treatment, and the relationship between response to preoperative chemotherapy and outcome were also evaluated. Results Two hundred sixteen patients received preoperative chemotherapy, 227 underwent immediate surgery. Fifty-nine percent of surgery only and 63% of chemotherapy plus surgery patients underwent R0 resections (P = .5137). Patients undergoing less than an R0 resection had an ominous prognosis; 32% of patients with R0 resections were alive and free of disease at 5 years, only 5% of patients undergoing an R1 resection survived for longer than 5 years. The median survival rates for patients with R1, R2, or no resections were not significantly different. While, as initially reported, there was no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group, patients with objective tumor regression after preoperative chemotherapy had improved survival. Conclusion For patients with localized esophageal cancer, whether or not preoperative chemotherapy is administered, only an R0 resection results in substantial long-term survival. Even microscopically positive margins are an ominous prognostic factor. After a R1 resection, postoperative chemoradiotherapy therapy offers the possibility of long-term disease-free survival to a small percentage of patients.
Assessing Individual Risk for Prostate Cancer
Authors: Nam Robert K. , Toi Ants , Klotz Laurence H. , Trachtenberg John , Jewett Michael A.S. , Appu Sree , Loblaw D. Andrew , Sugar Linda , Narod Steven A. , Kattan Michael W. 
Published: August 2007

Purpose To construct a clinical nomogram instrument to estimate individual risk for having prostate cancer (PC) for patients undergoing prostate specific antigen (PSA) screening, using all risk factors known for PC. Patients and Methods We conducted a cross-sectional study of 3,108 men who underwent a prostate biopsy, including a subset of 408 volunteers with normal PSA levels. Factors including age, family history of PC (FHPC), ethnicity, urinary symptoms, PSA, free:total PSA ratio, and digital rectal examination (DRE) were incorporated in the model. A nomogram was constructed to assess risk for any and high-grade PC (Gleason score ≥ 7). Results Of the 3,108 men, 1,304 (42.0%) were found to have PC. Among the 408 men with a normal PSA (< 4.0 ng/mL), 99 (24.3%) had PC. All risk factors were important predictors for PC by multivariate analysis (P, .01 to .0001). The area under the curve (AUC) for the nomogram in predicting cancer, which included age, ethnicity, FHPC, urinary symptoms, free:total PSA ratio, PSA, and DRE, was 0.74 (95% CI, 0.71 to 0.81) and 0.77 (95% CI, 0.74 to 0.81) for high-grade cancer. This was significantly greater than the AUC that considered using the conventional screening method of PSA and DRE only (0.62; 95% CI, 0.58 to 0.66 for any cancer; 0.69; 95% CI, 0.65 to 0.73 for high-grade cancer). From receiver operating characteristic analysis, risk factors including age, ethnicity, FHPC, symptoms, and free:total PSA ratio contributed significantly more predictive information than PSA and DRE. Conclusion In a PC screening program, it is important to consider age, family history of PC, ethnicity, urinary voiding symptoms, and free:total PSA ratio, in addition to PSA and DRE.
Toxicity of Older and Younger Patients Treated With Adjuvant Chemotherapy for Node-Positive Breast Cancer: The Cancer and Leukemia Group B Experience
Authors: Muss Hyman B. , Berry Donald A. , Cirrincione Constance , Budman Daniel R. , Henderson I. Craig , Citron Marc L. , Norton Larry , Winer Eric P. , Hudis Clifford A. 
Published: August 2007

Purpose Older node-positive patients treated with newer adjuvant chemotherapy regimens have improvements in relapse-free and overall survival similar to younger patients. We compared toxicity of older and younger patients in three randomized trials of adjuvant chemotherapy. Patients and Methods Toxicity data were available for 93% of 6,642 patients enrolled. The three trials included: Cancer and Leukemia Group B (CALGB) 8541, a comparison of cyclophosphamide, doxorubicin, and fluorouracil in three dose schedules; CALGB 9344: cyclophosphamide and doxorubicin with or without paclitaxel; and CALGB 9741: cyclophosphamide, doxorubicin, and paclitaxel every 2 versus every 3 weeks. National Cancer Institute grade 3 to 5 toxicities were compared among age groups. Results Seven percent of patients (n = 458) were age 65 or older, 3% were 70 or older, 38% were 51 to 64, and 55% were 50 or younger. Twenty-four deaths (0.4%) were attributed to treatment; seven (1.5%) of 486 in patients 65 or older, 10 (0.40%) of 2,480 in patients who were 51 to 64 years, and seven (0.19%) of 3,676 occurred in patients younger than 50. In multivariate analysis, older patients were significantly more likely to have grade 4 hematologic toxicity, to have discontinued treatment for toxicity, or to have died of acute myeloid leukemia/myelodysplastic syndrome. There were no significant differences in grade 3 to 4 nonhematologic toxicity. Conclusion Healthy older patients who met the strict eligibility criteria for these trials had a higher rate of hematologic toxicity and treatment-related deaths than younger patients, but no increase in nonhematologic toxicity. Elderly patients treated with newer adjuvant chemotherapy regimens derive the same benefits from newer chemotherapy regimens as younger patients but should be cautioned about the increased risk of toxicity and treatment-related death.
Combination of Polymorphisms From Genes Related to Estrogen Metabolism and Risk of Prostate Cancers: The Hidden Face of Estrogens
Authors: Cussenot Olivier , Azzouzi Abdel Rhamene , Nicolaiew Nathalie , Fromont Gaelle , Mangin Philippe , Cormier Luc , Fournier Georges , Valeri Antoine , Larre Stephane , Thibault Frederic , Giordanella Jean-Pierre , Pouchard Michel , Zheng Yan , Hamdy Freddie C. , Cox Angela , Cancel-Tassin Geraldine 
Published: August 2007

PurposeThe association between common functional polymorphisms from the CYP17, CYP19, CYP1B1, and COMT genes involved in the estrogen metabolism and the risk of prostate carcinoma was evaluated.Patients and MethodsThe study investigated 1,983 white French men (1,101 patients with prostate cancer and 882 healthy controls) aged between 40 and 98 years. The different alleles and genotypes were analyzed according to case-control status, aggressiveness pattern of the tumors, age at onset, and family history of cancers.ResultsThe VV (high activity) genotype of the V432L polymorphism from CYP1B1 (odds ratio [OR] = 1.36; 95% CI, 1.03 to 1.79; P = .031), and the long allele (> 175 bp) of the TTTA repeat from CYP19 (OR, 1.26; 95% CI, 1.08 to 1.47; P = .003) were significantly associated with the risk of prostate cancer. An additive effect was observed when we combined the two at-risk alleles (OR = 1.63; 95% CI, 1.24 to 2.13; P < .001). The association was stronger for the CYP1B1 VV genotype (OR = 1.55; 95% CI, 1.13 to 2.13; P = .007) among the group of patients with highly aggressive disease. Stratification by age at onset showed that the associations of CYP1B1 and CYP19 variants were largely confined to the younger prostate cancer patients.ConclusionThis association between polymorphisms from genes related to estrogen metabolism and prostate cancer risk suggest new clinical considerations in the management of prostate cancer: the development of new prevention trials based on genetic profiling and the evaluation of specific inhibitors involving the estrogen pathways.
Role of Human Papillomavirus Genotype in Prognosis of Early-Stage Cervical Cancer Undergoing Primary Surgery
Authors: Lai Chyong-Huey , Chang Chee-Jen , Huang Huei-Jean , Hsueh Swei , Chao Angel , Yang Jung-Erh , Lin Cheng-Tao , Huang Shang-Lang , Hong Ji-Hong , Chou Hung-Hsueh , Wu Tzu-I , Huang Kuan-Gen , Wang Chun-Chieh , Chang Ting-Chang 
Published: August 2007

Purpose Our aim was to evaluate the prognostic significance of human papillomavirus (HPV) genotype in early-stage cervical carcinoma primarily treated with surgery in a large tertiary referral medical center. Patients and Methods Consecutive patients who underwent primary surgery for invasive cervical carcinoma of International Federation of Gynecology and Obstetrics (FIGO) stage I to IIA between 1993 and 2000 were retrospectively reviewed. Polymerase chain reaction (PCR) using a general primer set followed by reverse-blot detection of 38 types of HPV DNA in a single reaction was performed for genotyping. E6 type-specific PCR was performed to validate multiple types. Results A total of 1,067 eligible patients were analyzed. HPV DNA sequences were detected in 95.1% of the specimens, among which 9.6% contained multiple types. HPV 16 was detected in 63.8% of the samples, and HPV 18 was detected in 16.5% of the samples. The median follow-up time of surviving patients was 77 months. By multivariate analysis, FIGO stage, lymph node metastasis, depth of cervical stromal invasion, grade of differentiation, and HPV 18 positivity were significantly related to cancer relapse. FIGO stage II, deep stromal invasion, parametrial extension, HPV 18 positivity, and age older than 45 years were significant predictors for death. Using the seven selected variables from either recurrence-free or overall survival analysis, death-predicting (P < .0001) and relapse-predicting (P < .0001) models classifying three risk groups (low, intermediate, and high risk) were constructed and endorsed by internal validation. Conclusion The independent prognostic value of HPV genotype is confirmed in this study. The prognostic models could be useful in counseling patients and stratifying patients in future clinical trials.
High Incidence of Cetuximab-Related Infusion Reactions in Tennessee and North Carolina and the Association With Atopic History
Authors: O'Neil Bert H. , Allen Robert , Spigel David R. , Stinchcombe Thomas E. , Moore Dominic T. , Berlin Jordan D. , Goldberg Richard M. 
Published: August 2007

Purpose To confirm the anecdotal observation that patients in North Carolina (NC) and Tennessee (TN) treated with cetuximab experience hypersensitivity reactions (HSR) at a much higher rate than are reported nationally and internationally (≤ 3%). Patients and Methods Data from patients treated with cetuximab on clinical trials (n = 88) at three research sites were analyzed for grade 3 or 4 HSR. Additional information was obtained from medical records for patients treated with cetuximab at the University of North Carolina (Chapel Hill, NC) to determine whether history of other significant allergy was a risk factor for HSR to cetuximab. Results Data for 88 patients on clinical trials and an additional 55 patients treated outside of trials were included in this analysis. Patients had a variety of tumor types. For the clinical trial group (n = 88), the overall rate of grade 3 to 4 HSR was 22%, significantly higher than the rate noted in any large published trial. All HSRs occurred during the first dose. There was a strong relationship between prior allergy history and chance of HSR. Conclusion At the sites in neighboring NC and TN studied, HSR was far more common than reported in national studies. History of prior allergy is a strong predictor of HSR. Further investigation of more specific predictors of HSR in the US middle south region is warranted, and patients being treated with cetuximab in this area should be observed particularly closely during their first infusion.
Phase III Study Comparing a Semimonthly With a Monthly Regimen of Fluorouracil and Leucovorin As Adjuvant Treatment for Stage II and III Colon Cancer Patients: Final Results of GERCOR C96.1
Authors: André Thierry , Quinaux Emmanuel , Louvet Christophe , Colin Philippe , Gamelin Erik , Bouche Olivier , Achille Emmanuel , Piedbois Pascal , Tubiana-Mathieu Nicole , Boutan-Laroze Arnaud , Flesch Michel , Lledo Gérard , Raoul Yves , Debrix Isabelle , Buyse Marc , de Gramont Aimery 
Published: August 2007

Purpose This randomized, 2 × 2 factorial study compared a semimonthly regimen (fluorouracil [FU] and leucovorin [LV] semi-monthly is LV5FU2) with a monthly regimen of FU and LV (mFU/LV) as well as 24 weeks versus 36 weeks of each regimen as adjuvant treatment of stage II and III colon cancer. Patients and Methods LV5FU2 was administered semimonthly for 2 days as racemate (dl) or levogyre (l-; 200 or 100 mg/m2) as a 2-hour infusion, followed by 400 mg/m2 FU bolus and a 600-mg/m2 FU 22-hour continuous infusion. FU and LV were administered monthly (mFU/LV) for 5 days as dl- or l-LV 15-minute infusion, followed by a 400 mg/m2 FU 15-minute infusion. The primary end point was disease-free survival (DFS). Results Between September 1996 and November 1999, 905 patients with stage II (43%) and III (57%) colon cancer were enrolled. The median follow-up was 6 years. There was no statistically significant difference between mFU/LV and LV5FU2 in terms of DFS (150 v 148 events; hazard ratio [HR],1.01; 95% CI, 0.806 to 1.269; P = .94) and overall survival (OS; 104 v 103 events; HR,1.02; 95% CI, 0.77 to 1.34; P = .91). No statistical difference was observed between 24 or 36 weeks of chemotherapy. Median survival from metastatic relapse was 24 months. The survival of patients with metastatic relapse (n = 243) was significantly longer for patients with a longer time from random assignment to relapse (< 1, 1 to 2, ≥ 2 years; log-rank test for trend P, .0497). Conclusion DFS and OS were not statistically different between treatment groups and treatment durations. These data confirm the value of LV5FU2 as control arm in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer and Pan-European Trials in Adjuvant Colon Cancer studies.
Antarctic fish can compensate for rising temperatures: thermal acclimation of cardiac performance in Pagothenia borchgrevinki
Authors: Franklin Craig E. , Davison William , Seebacher Frank 
Published: August 2007

SUMMARY
Antarctic fish Pagothenia borchgrevinki in McMurdo Sound,Antarctica, inhabit one of the coldest and most thermally stable of all environments. Sea temperatures under the sea ice in this region remain a fairly constant –1.86°C year round. This study examined the thermal plasticity of cardiac function in P. borchgrevinki to determine whether specialisation to stable low temperatures has led to the loss of the ability to acclimate physiological function. Fish were acclimated to–1°C and 4°C for 4–5 weeks and cardiac output was measured at rest and after exhaustive exercise in fish acutely transferred from their acclimation temperature to –1, 2, 4, 6 and 8°C. In the–1°C acclimated fish, the factorial scope for cardiac output was greatest at –1°C and decreased with increasing temperature. Increases in cardiac output with exercise in the –1°C acclimated fish was achieved by increases in both heart rate and stroke volume. With acclimation to 4°C, resting cardiac output was thermally independent across the test temperatures; furthermore, factorial scope for cardiac output was maintained at 4, 6 and 8°C, demonstrating thermal compensation of cardiac function at the higher temperatures. This was at the expense of cardiac function at –1°C, where there was a significant decrease in factorial scope for cardiac output in the 4°C acclimated fish. Increases in cardiac output with exercise in the 4°C acclimated fish at the higher temperatures was achieved by changes in heart rate alone, with stroke volume not varying between rest and exercise. The thermal compensation of cardiac function in P. borchgrevinki at higher temperatures was the result of a change in pumping strategy from a mixed inotropic/chronotropic modulated heart in –1°C acclimated fish at low temperatures to a purely chronotropic modulated heart in the 4°C acclimated fish at higher temperatures. In spite of living in a highly stenothermal cold environment, P. borchgrevinki demonstrated the capacity to thermally acclimate cardiac function to elevated temperatures, thereby allowing the maintenance of factorial scope and the support of aerobic swimming at higher temperatures.
Distance, shape and more: recognition of object features during active electrolocation in a weakly electric fish
Authors: von der Emde Gerhard , Fetz Steffen 
Published: August 2007

SUMMARYIn the absence of light, the weakly electric fish Gnathonemus petersii detects and distinguishes objects in the environment through active electrolocation. In order to test which features of an object the fish use under these conditions to discriminate between differently shaped objects,we trained eight individuals in a food-rewarded, two-alternative,forced-choice procedure. All fish learned to discriminate between two objects of different shapes and volumes. When new object combinations were offered in non-rewarded test trials, fish preferred those objects that resembled the one they had been trained to (S+) and avoided objects resembling the one that had not been rewarded (S–). For a decision, fish paid attention to the relative differences between the two objects they had to discriminate. For discrimination, fish used several object features, the most important ones being volume, material and shape. The importance of shape was demonstrated by reducing the objects to their 3-dimensional contours, which sufficed for the fish to distinguish differently shaped objects. Our results also showed that fish attended strongly to the feature `volume', because all individuals tended to avoid the larger one of two objects. When confronted with metal versus plastic objects, all fish avoided metal and preferred plastic objects, irrespective of training. In addition to volume, material and shape,fish attended to additional parameters, such as corners or rounded edges. When confronted with two unknown objects, fish weighed up the positive and negative properties of these novel objects and based their decision on the outcome of this comparison. Our results suggest that fish are able to link and assemble local features of an electrolocation pattern to construct a representation of an object, suggesting that some form of a feature extraction mechanism enables them to solve a complex object recognition task.
Temperature adaptation in two bivalve species from different thermal habitats: energetics and remodelling of membrane lipids
Authors: Pernet Fabrice , Tremblay Réjean , Comeau Luc , Guderley Helga 
Published: August 2007

SUMMARYWe compared lipid dynamics and the physiological responses of blue mussels Mytilus edulis, a cold-adapted species, and oysters Crassostrea virginica, a warmer-water species, during simulated overwintering and passage to spring conditions. To simulate overwintering, animals were held at 0°C, 4°C and 9°C for 3 months and then gradually brought to and maintained at 20°C for 5 weeks to simulate spring–summer conditions. Changes in lipid class and fatty acid composition were related to clearance rate and oxygen consumption.We found major differences between species in triglyceride (TAG) metabolism during overwintering. Mussels used digestive gland TAG stores for energy metabolism or reproductive processes during the winter, whereas oysters did not accumulate large TAG stores prior to overwintering. Mussel TAG contained high levels of 20:5n-3 compared to levels in oysters and in the diet. This may help to counteract the effect of low temperature by reducing the melting point of TAG and thus increasing the availability of storage fats at low temperature. Mussels seemed better able to mobilise 20:5n-3 and 18:4n-3 than other fatty acids.We also found that both bivalves underwent a major remodelling of membrane phospholipids. The unsaturation index decreased in the gills and digestive glands of both species during the early stages of warming, principally due to decreases in 22:6n-3 and 20:5n-3. In digestive glands, the unsaturation index did not increase with decreasing temperature beyond a threshold attained at 9°C whereas a perfect negative relationship was observed in gills, as predicted by homeoviscous adaptation. The presence of digestive enzymes and acids in the digestive gland microenvironment may lead to specific requirements for membrane stability. That oysters had lower metabolic rates than mussels coincides with a lower unsaturation index of their lipids, as predicted by Hulbert's theory of membranes as metabolic pacemakers. Both species showed increased 20:4n-6 levels in their tissues as temperature rose,suggesting an increasing availability of this fatty acid for eicosanoid biosynthesis during stress responses.The contrast between the species in TAG dynamics and the similarity of their phospholipid remodelling emphasises the essential functional role of membrane phospholipid structure and the contrasting use of TAG by oysters and mussels during overwintering.