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Background: The aim of this study is to evaluate the effectiveness of TachoSil sponge on distal pancreatectomy remnant stump in reducing the rate and severity of postoperative pancreatic fistula (POPF)., Methods: All consecutive patients requiring distal pancreatectomy were randomized in 45 centers. The principal end point was onset of "clinically relevant" POPF. Univariate and multivariate analyses were searched for predictive factors., Results: Of the 270 patients randomized (134 with TachoSil; 136 without), 150 (55.6%) patients sustained a POPF [74 clinically relevant and 76 clinically silent (27.4% and 28.1%), respectively]: no statistically significant difference was found between patients sustaining clinically relevant POPF [41 (30.6%) with vs 33 (24.3%) without TachoSil (P = .276)], or overall POPF [73 (54.5%) with vs 77 (56.6%) without TachoSil, (P = .807)], but there were more clinically relevant POPF after hand-sewn (32.3%) versus mechanical closure (19.8%) (P = .025) and, in case of splenic preservation, after splenic vessel ligation (15/32, 46.9%) versus vascular preservation (17/72, 23.6%) (P = .024). Hand-sewn pancreatic remnant closure (P = .023) and splenic vessel ligation in splenic preservation (P = .035) were independent predictive factors for the onset of clinically relevant POPF., Conclusion: TachoSil sponge reinforcement of the proximal remnant after distal pancreatectomy reduced neither the rate nor the severity of POPF., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer., Methods: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9)., Results: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items., Conclusion: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background and Aim: The use of abdominal binders after laparotomy is a question of habit. Scientific evidence of their usefulness is limited. The aims of this work were to review the scientific literature and to depict the practices of French surgeons regarding the use of these devices., Methods: A systematic review of the literature about the use of abdominal binders after laparotomy was conducted. In order to depict surgeons' habits, an anonymous questionnaire was sent to all surgical departments affiliated to the FRENCH network (Federation of Surgical Research) and their surgical contacts. They were all asked about their use of binders, the type of binders they ordered, the expected benefit, the cost and the need for a randomized trial in this field., Results: Only four trials have been published regarding the use of abdominal binders after laparotomy, all with a small number of patients. Some authors suggested that wearing binders procured a benefit in terms of postoperative comfort, but no significant difference was found. One study also suggested an improvement in respiratory volumes. No study focused on incisional hernia. Regarding the survey of practices, 50 questionnaires were retained for the final analysis (one questionnaire per department of surgery). The use of this device is really very frequent in France (94 % of surgeons order them), a habit usually acquired during the training in surgery. The main expected benefit is the prevention of abdominal wall dehiscence (83 %), but also an improvement in patients' postoperative comfort and pain (66 %). Although some surgeons order an abdominal binder for all their patients, most use them in selected patients (according to the operation and the patients' characteristics)., Conclusion: Abdominal binders are frequently ordered by French surgeons after laparotomy. The expected benefit is the prevention of abdominal-wall complications, even though no data actually support this practice. Binders might have a benefit in terms of postoperative pain relief, but this needs to be analyzed. A prospective randomized trial is warranted.

Purpose: Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma, but the optimal duration and time to initiate chemotherapy is unknown., Patients and Methods: Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they had been randomly assigned to chemotherapy. Overall survival analysis was performed on an intention-to-treat basis, retaining patients in their randomized groups, and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy., Results: There were 985 patients, of whom 486 (49%) received gemcitabine and 499 (51%) received fluorouracil; 675 patients (68%) completed all six cycles of chemotherapy (full course) and 293 patients (30%) completed one to five cycles. Lymph node involvement, resection margins status, tumor differentiation, and completion of therapy were all shown by multivariable Cox regression to be independent survival factors. Overall survival favored patients who completed the full six courses of treatment versus those who did not (hazard ratio [HR], 0.516; 95% CI, 0.443 to 0.601; P < .001). Time to starting chemotherapy did not influence overall survival rates for the full study population (HR, 0.985; 95% CI, 0.956 to 1.015). Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy, in favor of later treatment (P < .001)., Conclusion: Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma. There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery.

Background: Despite the prevalence of complex ventral hernias, there is little agreement on the most appropriate technique or prosthetic to repair these defects, especially in contaminated fields. Our objective was to determine French surgical practice patterns among academic surgeons in complex ventral hernia repair (CVHR) with regard to indications, most appropriate techniques, choice of prosthesis, and experience with complications., Methods: A survey consisting of 21 questions and 6 case-scenarios was e-mailed to French practicing academic surgeons performing CVHR, representing all French University Hospitals., Results: Forty over 54 surgeons (74%) responded to the survey, representing 29 French University Hospitals. Regarding the techniques used for CVHR, primary closure without reinforcement was provided in 31.6% of cases, primary closure using the component separation technique without mesh use in 43.7% of cases, mesh positioned as a bridge in 16.5% of cases, size reduction of the defect by using aponeurotomy incisions without mesh use in 8.2% of cases. Among the 40 respondents, 36 had experience with biologic mesh. There was a strong consensus among surveyed surgeons for not using synthetic mesh in contaminated or dirty fields (100%), but for using it in clean settings (100%). There was also a strong consensus between respondents for using biologic mesh in contaminated (82.5%) or infected (77.5%) fields and for not using it in clean setting (95%). In clean-contaminated surgery, there was no consensus for defining the optimal therapeutic strategy in CVHR. Infection was the most common complication reported after biologic mesh used (58%). The most commonly reported influences for the use of biologic grafts included literature, conferences and discussion with colleagues (85.0%), personal experience (45.0%) and cost (40.0%)., Conclusions: Despite a lack of level I evidence, biologic meshes are being used by 90% of surveyed surgeons for CVHR. Importantly, there was a strong consensus for using them in contaminated or infected fields and for not using them in clean setting. To better guide surgeons, prospective, randomized trials should be undertaken to evaluate the short- and long-term outcomes associated with these materials in various surgical wound classifications., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection., Methods: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided., Results: Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)₁= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)₁ = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)₁ = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients., Conclusions: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

Context: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas., Objective: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection., Design, Setting, and Patients: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers., Interventions: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months., Main Outcome Measures: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life., Results: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03)., Conclusions: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy., Trial Registration: clinicaltrials.gov Identifier: NCT00058201.

A recent examination of a bilioportal fistula led us to suspect a link between this case and the death of Ignatius of Loyola. Realdo Colombo, professor of anatomy, eviscerated Ignatius prior to his embalming In his book De re anatomica, published in 1559, he wrote that he extracted stones from the portal vein of the venerable Ignatius. Before his death, Ignatius suffered from epigastric pain and fever (Monumenta historica societatis Jesu). Colombo latin text is difficult to interpret and the data are meager. Other possible causes of Ignatius' death include gastroduodenal ulcer, tuberculosis and hyperparathyroidism, but despite of rarity bilioportal fistula is the best guess.

Background: Prosthetic reinforcement is the gold standard treatment for inguinal hernia and reduces the risk of recurrence. Yet up to one-third of patients complain of post-surgical pain due to irritation and inflammation caused by the mesh and the fixation materials. Of these patients, 3-4% will experience severe and disabling chronic pain. We performed a prospective multicenter clinical study of a self-adhering prosthesis, consisting of a lightweight polypropylene mesh (40 g/m²) coated on each side with synthetic glue, to evaluate early postoperative complications and patient outcomes., Patients and Methods: Between August 2008 and June 2010, 186 patients underwent hernia repair using the Lichtenstein technique and the self-adhering prosthesis. Primary endpoints were the frequency of disabling complications and quality of life (QoL) at 3-month follow-up. Pain, numbness, and groin discomfort were evaluated pre- and postoperatively (1 week, 1 and 3 months) using a visual analogue scale (VAS). Patients' pre- and postoperative QoL were measured using the SF12 questionnaire. Secondary endpoints were number of complications and recurrence rate, use of analgesic drugs, length of hospital stay, delay to return to normal activities, and patient satisfaction. The quality of the self-adhering mesh and its clinical utility were also evaluated by the participating surgeons., Results: A total of 186 patients were enrolled and followed for at least 3 months after inguinal hernia repair. A total of 174 (95%) primary hernias and 12 (5%) recurrent hernias were treated. There were no intraoperative complications, no recurrences, and no repeat interventions performed during the study. The post-surgical complication rate was 4.5%. The mean delay to recover normal physical activity was 4 days. For the primary endpoint of pain, a VAS of zero was reported by 93/184 (50.5%) patients at 1 week, 130/171 (76.0%) patients at 1 month and 119/132 (90.2%) patients at 3 months' follow-up (P < 0.0001). The postoperative SF12 scores showed a significant improvement in patient QoL following surgery (P < 0.0001)., Conclusions: Adhesix( ® ) self-adhering mesh for prosthetic reinforcement following inguinal hernia repair is atraumatic and associated with infrequent post-surgical complications or pain, a rapid recovery rate, and a high patient-reported QoL. A longer follow-up is underway to assess the frequency of post-surgical recurrence.

Background and Study Aims: To summarize the published literature on assessment of appropriateness of colonoscopy for surveillance after polypectomy and after curative-intent resection of colorectal cancer (CRC), and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II., Methods: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of surveillance colonoscopy after polypectomy and after resection of CRC was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions., Results: Most CRCs arise from adenomatous polyps. The characteristics of removed polyps, especially the distinction between low-risk adenomas (1 or 2, small [< 1 cm], tubular, no high-grade dysplasia) vs. high-risk adenomas (large [> or = 1 cm], multiple [> 3], high-grade dysplasia or villous features), have an impact on advanced adenoma recurrence. Most guidelines recommend a 3-year follow-up colonoscopy for high-risk adenomas and a 5-year colonoscopy for low-risk adenomas. Despite the lack of evidence to support or refute any survival benefit for follow-up colonoscopy after curative-intent CRC resection, surveillance colonoscopy is recommended by most guidelines. The timing of the first surveillance colonoscopy differs. The expert panel considered that 56 % of the clinical indications for colonoscopy for surveillance after polypectomy were appropriate. For surveillance after CRC resection, it considered colonoscopy appropriate 1 year after resection., Conclusions: Colonoscopy is recommended as a first-choice procedure for surveillance after polypectomy by all published guidelines and by the EPAGE II criteria. Despite the limitations of the published studies, colonoscopy is also recommended by most of the guidelines and by EPAGE II criteria for surveillance after curative-intent CRC resection.

F. Lacaine Lymph node metastasis carries enormous prognostic weight in the evaluation of colon cancer and raises the question of how extensive a lymph node dissection should be. Lymph node dissection has several goals: 1) staging of the cancer at the time of intervention; 2) improving the chances for complete resection and cure; 3) evaluating the thoroughness and quality of a particular surgical procedure. The prognostic value of lymphadenectomy is evident from the direct practical decisions it entails: evidence-based recommendations (Level A) have proposed adjuvant chemotherapy for all patients with Stage III colon cancer since 1990. Studies have shown a statistically significant correlation between the number of nodes examined in an operative specimen and long-term survival in patients with Stage II disease. The more closely lymph nodes are examined, the more metastasis is found; one can then see the aberrations of stage migration described as the "Will Rogers Phenomenon." Without randomized studies, it is impossible to say whether resection of a larger number of lymph nodes actually improves the prognosis or whether that number is simply a marker of better surgical management including the quality of the surgical gesture, the careful pathologic examination of the specimen, and subsequent choices for adjuvant chemotherapy. The recovery of 12 lymph nodes correlates with a better global prognosis. At the very least, it is an effective marker for the quality of the surgical resection and can be used in the evaluation of professional practice., (Copyright © 2008 Elsevier Masson SAS. All rights reserved.)

F. Lacaine Lymph node metastasis carries enormous prognostic weight in the evaluation of colon cancer and raises the question of how extensive a lymph node dissection should be. Lymph node dissection has several goals: 1) staging of the cancer at the time of intervention; 2) improving the chances for complete resection and cure; 3) evaluating the thoroughness and quality of a particular surgical procedure. The prognostic value of lymphadenectomy is evident from the direct practical decisions it entails: evidence-based recommendations (Level A) have proposed adjuvant chemotherapy for all patients with Stage III colon cancer since 1990. Studies have shown a statistically significant correlation between the number of nodes examined in an operative specimen and long-term survival in patients with Stage II disease. The more closely lymph nodes are examined, the more metastasis is found; one can then see the aberrations of stage migration described as the "Will Rogers Phenomenon." Without randomized studies, it is impossible to say whether resection of a larger number of lymph nodes actually improves the prognosis or whether that number is simply a marker of better surgical management including the quality of the surgical gesture, the careful pathologic examination of the specimen, and subsequent choices for adjuvant chemotherapy. The recovery of 12 lymph nodes correlates with a better global prognosis. At the very least, it is an effective marker for the quality of the surgical resection and can be used in the evaluation of professional practice., (Copyright © 2008 Elsevier Masson SAS. All rights reserved.)

Lymph node metastasis carries enormous prognostic weight in the evaluation of colon cancer and raises the question of how extensive a lymph node dissection should be. Lymph node dissection has several goals: 1) staging of the cancer at the time of intervention; 2) improving the chances for complete resection and cure; 3) evaluating the thoroughness and quality of a particular surgical procedure. The prognostic value of lymphadenectomy is evident from the direct practical decisions it entails: evidence-based recommendations (Level A) have proposed adjuvant chemotherapy for all patients with Stage III colon cancer since 1990. Studies have shown a statistically significant correlation between the number of nodes examined in an operative specimen and long-term survival in patients with Stage II disease. The more closely lymph nodes are examined, the more metastasis is found; one can then see the aberrations of stage migration described as the "Will Rogers Phenomenon." Without randomized studies, it is impossible to say whether resection of a larger number of lymph nodes actually improves the prognosis or whether that number is simply a marker of better surgical management including the quality of the surgical gesture, the careful pathologic examination of the specimen, and subsequent choices for adjuvant chemotherapy. The recovery of 12 lymph nodes correlates with a better global prognosis. At the very least, it is an effective marker for the quality of the surgical resection and can be used in the evaluation of professional practice.

We have assessed the possibility to build a prognosis predictor (PP), based on non-neoplastic mucosa microarray gene expression measures, for stage II colon cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10 with a metachronous metastasis, 14 with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into 1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Mean prognosis prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for sensitivity and 87.1% for specificity. Informative genes suggested branching signal-transduction pathways with possible extensive networks between individual pathways. They also included genes coding for proteins involved in immune surveillance. In conclusion, our study suggests that one can build an accurate PP for stage II colon cancer patients, based on non-neoplastic mucosa microarray gene expression measures.

This study seeks to evaluate the time interval between initial inguinal hernia repair and the appearance of recurrent hernia in patients undergoing re-operation. Recurrent hernia was identified in 94 (6.4%) of 1,474 patients having undergone initial hernia repair at our institution. Recurrence appeared within two years in 40 patients (42%). Recurrences were noted beyond five years in 32 patients (34%), and after 20 years in 18 patients (19%). 75% of recurrences had occurred within 15 years. We conclude that almost two-thirds of recurrences occur later than five years after the initial intervention and a quarter occur at an interval of more than fifteen years. Most studies underestimate hernia recurrence due to an insufficient period of post-operative observation.

Aim and Methods: Are physicians and their relatives at risk of postoperative complications when they are scheduled for surgery? With the aim to answer this question, a case control study was performed from a cohort of 11,756 patients scheduled for surgery from 01/01/1987 to 12/31/2002. Fourty seven patients were physicians and 122 were a close relative to a physician. The percentage of physicians in the current series is comparable to that in the general urban population in France. Each of these patients was matched with 5 patients as controls regarding sex, age, diagnosis, procedure, and date of surgery., Results: No statistically significant difference was observed between the 47 physicians and their 235 controls in the occurence of postoperative complications: 6% vs 6% (Odds ratio (OR)=1,07; CI(95%): 0,28-3,74), unplanned return to the operative room: 2% vs 2% (OR=1,00; CI: 0,11-8,8), and postoperative mortality: 0% vs 0,5% (p=0,07). No stastistically significant difference was observed between the 122 close relatives to a physician and their 610 controls in the occurence of postoperative complications: 6% vs 6% (OR=1,00; CI: 0,43-2,3), unplanned return to the operative room: 2% vs 3% (OR=0,55; CI: 0,18-3,4), and postoperative mortality: 1% vs 0,5% (OR=1,67; CI: 0,13-12,12)., Conclusion: this study does not confirm the widespread opinion that postoperative course would be worse in physicians as patients and in their close relatives. Their recovery is not different from that to other patients if they are treated as well as other patients.

Background: Ischemic colitis almost always occurs in older patients. Because life expectancy is increasing, more and more often physicians will face this problem. The aim of this study was to identify factors leading to surgery in the acute phase of the disease, and to evaluate mortality and long-term follow-up evaluation., Methods: We performed a retrospective study of 73 patients (mean age, 73 y) in the Department of General and Digestive Surgery. Diagnosis was obtained by endoscopic and pathologic procedures. The median follow-up period was 4.5 years (range, 2-9 y)., Results: Thirty-six patients had 1 or more co-existing medical diseases. All the patients had either lower intestinal bleeding (45 patients) or diarrhea (28 patients). Thirty-three patients had undergone surgery (45%). In the surgical group, 13 patients underwent immediate surgery for abdominal tenderness and/or shock. Eight of these patients died (62%). Out of 60 patients undergoing nonsurgical immediate management, 1 patient died (septic shock). Delayed surgery was indicated in 20 out of the 59 remaining patients for clinical or endoscopic aggravation. Six of these patients died (30%). Multivariate analysis selected 4 factors of severity: age younger than 80 years, male sex, absence of bleeding, and abdominal tenderness. In the follow-up period 13 patients died from a cardiovascular disease. The 2- and 5-year actuarial survival rates of patients who survived the initial hospitalization were 88% and 68%, respectively., Conclusions: Multivariate analysis selected the risk factors of severity. In severely ill patients serial endoscopic evaluations are the best indicator for surgery before appearance of tenderness, septic shock, full-thickness gangrene, and perforation. At discharge, anticoagulant or anti-arrhythmic therapy should be considered for patients who have cardiovascular disease.

Purpose: This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated., Patients and Methods: Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes., Results: The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy., Conclusion: Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.

Purpose: This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in Stage II and III colon cancer patients., Methods: Tumor and nonneoplastic mucosa mRNA samples from 12 colon cancer patients were profiled using the Affymetrix HGU133A GeneChip. Six of 12 patients experienced a metachronous metastasis, whereas the 6 others remained disease-free for more than five years. Three datasets were constituted, including, respectively, the gene expression measures in tumor samples (T), in adjacent nonneoplastic mucosa samples (A), and the log-ratio of the gene expression measures (L). The step-down procedure of Westfall and Young and the k-nearest neighbor class prediction method were applied on T, A, and L. Leave-one-out cross-validation was used to estimate the generalization error of predictors based on different numbers of genes and neighbors., Results: The most frequent results were one false prediction with the A-based predictors (95 percent) and two false predictions with the T- and L: -based predictors (65 and 60 percent, respectively). A-based predictors were more stable (i.e., less sensitive to changes of parameters, such as numbers of genes and neighbors) than T- and L: -based predictors. Informative genes in A-based predictors included genes involved in the oxidative and phosphorylative mitochondrial metabolism and genes involved in cell-signaling pathways and their receptors., Conclusions: This study suggests that one can build a prognosis predictor for Stage II and III colon cancer patients, based on microarray gene expression measures, and suggests the potential usefulness of nonneoplastic mucosa for this purpose.

This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in stage II and III colon cancer patients. Tumour (T) and non-neoplastic mucosa (NM) mRNA samples from 18 patients (nine with a recurrence, nine with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. The k-nearest neighbour method was used for prognosis prediction using T and NM gene expression measures. Six-fold cross-validation was applied to select the number of neighbours and the number of informative genes to include in the predictors. Based on this information, one T-based and one NM-based predictor were proposed and their accuracies were estimated by double cross-validation. In six-fold cross-validation, the lowest numbers of informative genes giving the lowest numbers of false predictions (two out of 18) were 30 and 70 with the T and NM gene expression measures, respectively. A 30-gene T-based predictor and a 70-gene NM-based predictor were then built, with estimated accuracies of 78 and 83%, respectively. This study suggests that one can build an accurate prognosis predictor for stage II and III colon cancer patients, based on gene expression measures, and one can use either tumour or non-neoplastic mucosa for this purpose.

There are now five classic steps for analysis of diagnostic and therapeutic medical decision-making policies: (1) formulate a clear clinical question based on a particular patient's problem; (2) search the literature for relevant clinical articles; (3) evaluate the evidence for its validity and usefulness; (4) implement useful findings into clinical practice; (5) audit the validity of the process. The clinician must have the necessary skills to appraise critically the information retrieved. Rather than focusing on the discussion and conclusion sections of articles, the reader should concentrate on the review of the methods and results sections to formulate an opinion regarding the strength of evidence presented in the paper. The process is intellectually demanding and difficult to achieve. This particular step in the validation of evidence implies that each clinician must be methodologically and statistically sound, an "expert," capable of analyzing the method used in that particular publication to achieve the published result.

Background/aims: 18Fluorodeoxyglucose positron emission tomography has been proposed for the preoperative staging of carcinomas of the esophagus and gastric cardia. The aim of this study was to assess its diagnostic value and its influence on therapeutical decisions., Methodology: Twenty-eight patients with a cancer of the esophagus or gastric cardia underwent a 18Fluorodeoxyglucose positron emission tomography on a gamma camera with coincidence detection electronics, in addition to our standard preoperative procedures (barium swallow, liver ultrasonography, chest X-ray). Four types of lesions were searched for: primary tumor, abdominal and mediastinal lymph nodes, and distant metastases. Results of 18Fluorodeoxyglucose positron emission tomography were compared to pathological findings., Results: Sensitivity for the primary tumor was 86%. Sensitivity for mediastinal and abdominal lymph nodes was 75 and 54%, respectively, whereas specificity was 100%. Distant metastases were detected in 4 patients: liver metastasis in 2 patients and bone metastasis in 2 patients. Results of 18Fluorodeoxyglucose positron emission tomography influenced therapeutical decisions for 2 patients., Conclusions: 18Fluorodeoxyglucose positron emission tomography seems to be worthwhile in the preoperative staging of carcinomas of the esophagus and gastric cardia, mainly because it may detect distant metastases.

Background: The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results., Methods: In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation., Results: The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors., Conclusions: Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival., (Copyright 2004 Massachusetts Medical Society)

The results from pancreatic ductal adenocarcinoma appear to be improving with increased resection rates and reduced postoperative mortality reported by specialist pancreatic cancer teams. Developments with medical oncological treatments have been difficult, however, due to the fundamentally aggressive biological nature of pancreatic cancer and its resistance to chemotherapy coupled with a relative dearth of randomised controlled trials. The European Study Group for Pancreatic Cancer (ESPAC)-1 trial recruited nearly 600 patients and is the largest trial in pancreatic cancer. The results demonstrated that the current best adjuvant treatment is chemotherapy using bolus 5-fluorouracil with folinic acid. The median survival of patients randomly assigned to chemoradiotherapy was 15.5 months and is comparable with many other studies, but the median survival in the chemotherapy arm was 19.7 months and is as good or superior to multimodality treatments including intra-operative radiotherapy, adjuvant chemoradiotherapy and neo-adjuvant therapies. The use of adjuvant 5-fluorouracil with folinic acid may be supplanted by gemcitabine but requires confirmation by ongoing clinical trials, notably ESPAC-3, which plans to recruit 990 patients from Europe, Canada and Australasia. Major trials such as ESPAC-1 and ESPAC-3 have set new standards for the development of adjuvant treatment and it is now clear that such treatment in this field has the potential to significantly improve both patient survival and quality of life after curative resection.

Contrary to the fears raised in surgical publications of the 1950's and 60's, the prognosis of porcelain gallbladder is not automatically associated with an increased risk of gallbladder carcinoma. Two recent cohort studies have allowed a better definition of the appropriate therapeutic attitude for a patient with a calcified gallbladder. In cases of "true" porcelain gallbladder, i.e., the presence of complete transmural calcification of the entire gallbladder wall, indications for cholecystectomy are based on biliary symptoms, all the more so since choledocholithiasis is often associated with porcelain gallbladder. In the case of partial calcification of the gallbladder, i.e., focal plaques of calcification involving the mucosa, prophylatic operative treatment is indicated. In these cases, the incidence of malignancy is markedly increased (14 times that of a control population). Cholecystectomy can still be performed laparascopically as long as the rules for prevention of peritoneal dissemination of tumor cells are scrupulously observed--the gallbladder should not be opened nor bile spilled, the specimen should be placed in a bag for removal through the abdominal wall, the pneumoperitoneum should be evacuated with the trocars still in place and the specimen should be opened and examined after removal with immediate frozen section pathologic exam if there is any question of tumor.

Background: This retrospective study aimed to compare the prognosis for rectal cancer in patients more than 80 years old with that observed in younger patients., Methods: Patients operated on for a rectal adenocarcinoma, from 1980 to 1998, were divided into two groups: group 1 (>80 years, n = 92); group 2 (<80 years, n = 276)., Results: There were significant differences between the two groups with regard to the sex ratio, the American Society of Anesthesiologists (ASA) classification, the emergency presentation, and the curative operation rate. The operative mortality rate was 8% in group 1, 4% in group 2 (P = 0.26). The overall 5-year survival rate was 35% in group 1, 53% in group 2 (P = 0.0004). In patients operated on for cure, the cancer-specific 5-year survival rate was 50% in group 1, 59% in group 2 (P = 0.08)., Conclusions: The prognosis for rectal cancer in patients over 80 years is not significantly different from that of younger patients. Surgery should not be restricted on the basis of age.

Frequency of local and distant failures after gastrectomy has led to extended lymph nodes dissection to obtain a better locoregional control. However, five year survival rates were not significantly different between patients undergoing D2 and D1 lymphadenectomy, and higher morbidity and post operative deaths were reported in large randomised trials (respectively 25% vs 48% and 4 vs 13%). Additionally, several metanalysis failed to demonstrate a significant survival advantage with adjuvant chemotherapy. The results of the first trial demonstrating one advantage to adjuvant post-operative chemoradiotherapy should modify the standard care. Disease free and overall survival after surgery alone and after surgery and concurrent chemoradiotherapy were respectively 31% vs 48% and 41% vs 50%. The intergroup trial demonstrate that better local control improve survival if radiation fields include stamps, tumour bed, proximal nodal chains and nodes corresponding to D2 extended lymph nodes dissection. Treatment was feasible with few severe toxic effects (1%). Of the 281 patients, 17% stopped treatment because toxic effects. Technical modalities of radiotherapy and post-operative nutrition support, which are critical points of interest for this treatment, are also discussed.

Objective: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study., Summary Background Data: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies., Methods: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status., Results: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups., Conclusions: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.

Background: The role of adjuvant treatment in pancreatic cancer remains uncertain. The European Study Group for Pancreatic Cancer (ESPAC) assessed the roles of chemoradiotherapy and chemotherapy in a randomised study., Methods: After resection, patients were randomly assigned to adjuvant chemoradiotherapy (20 Gy in ten daily fractions over 2 weeks with 500 mg/m(2) fluorouracil intravenously on days 1-3, repeated after 2 weeks) or chemotherapy (intravenous fluorouracil 425 mg/m(2) and folinic acid 20 mg/m(2) daily for 5 days, monthly for 6 months). Clinicians could randomise patients into a two-by-two factorial design (observation, chemoradiotherapy alone, chemotherapy alone, or both) or into one of the main treatment comparisons (chemoradiotherapy versus no chemoradiotherapy or chemotherapy versus no chemotherapy). The primary endpoint was death, and all analyses were by intention to treat. Findings 541 eligible patients with pancreatic ductal adenocarcinoma were randomised: 285 in the two-by-two factorial design (70 chemoradiotherapy, 74 chemotherapy, 72 both, 69 observation); a further 68 patients were randomly assigned chemoradiotherapy or no chemoradiotherapy and 188 chemotherapy or no chemotherapy. Median follow-up of the 227 (42%) patients still alive was 10 months (range 0-62). Overall results showed no benefit for adjuvant chemoradiotherapy (median survival 15.5 months in 175 patients with chemoradiotherapy vs 16.1 months in 178 patients without; hazard ratio 1.18 [95% CI 0.90-1.55], p=0.24). There was evidence of a survival benefit for adjuvant chemotherapy (median survival 19.7 months in 238 patients with chemotherapy vs 14.0 months in 235 patients without; hazard ratio 0.66 [0.52-0.83], p=0.0005). Interpretation This study showed no survival benefit for adjuvant chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy, justifying further randomised controlled trials of adjuvant chemotherapy in pancreatic cancer.

General Design: Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). A randomised, placebo controlled, double-blinded, single-centre study is performed at an University Hospital (n = 40 patients for each group). This part presents the course of the individual patient and a complication algorithm for the management of anastomotic leakage and quality management., Objective: In part three of the protocol, the three major sections include: The course of the individual patient using a comprehensive graphic display, including the perioperative period, hospital stay and post discharge outcome. A center based clinical practice guideline for the management of the most important postoperative complication--anastomotic leakage--including evidence based support for each step of the algorithm. Data management, ethics and organisational structure., Conclusions: Future studies with immune modifiers will also fail if not better structured (reduction of variance) to achieve uniform patient management in a complex clinical scenario. This new type of a single-centre trial aims to reduce the gap between animal experiments and clinical trials or--if it fails--at least demonstrates new ways for explaining the failures.