Perioperative FOLFOX 4 Versus FOLFOX 4 Plus Cetuximab Versus Immediate Surgery for High-Risk Stage II and III Colon Cancers: A Phase II Multicenter Randomized Controlled Trial (PRODIGE 22).

BACKGROUND: Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC). OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients with locally advanced nonmetastatic CC. METHODS: This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery. RESULTS: A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P < 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group. CONCLUSIONS: Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients.

Influence of Molecular Status on Recurrence Site in Patients Treated for a Stage III Colon Cancer: a Post Hoc Analysis of the PETACC-8 Trial.

BACKGROUND: Recurrence patterns in stage III colon cancer (CC) patients according to molecular markers remain unclear. The objective of the study was to assess recurrence patterns according to microsatellite instability (MSI), RAS and BRAFV600E status in stage III CC patients. METHODS: All stage III CC patients from the PETACC-8 randomized trial tested for MSI, RAS and BRAFV600E status were included. The site and characteristics of recurrence were analyzed according to molecular status. Survival after recurrence (SAR) was analyzed. RESULTS: A total of 1650 patients were included. Recurrence occurred in 434 patients (26.3%). Microsatellite stable (MSS) patients had a significantly higher recurrence rate (27.2% vs. 18.7%, P = 0.02) with a trend to more pulmonary recurrence (28.8% vs. 12.9%, P = 0.06) when compared to MSI patients. MSI patients experienced more regional lymph nodes compared to MSS (12.9% vs. 4%, P = 0.046). In the MSS population, the recurrence rate was significantly higher in RAS (32.2%) or BRAF (32.3%) patients when compared to double wild-type patients (19.9%) (p < 0.001); no preferential site of recurrence was observed according to RAS and BRAFV600E mutations. Finally, decreased SAR was observed in the case of peritoneal recurrence or more than two recurrence sites. CONCLUSIONS: Microsatellite, RAS and BRAFV600E status influences recurrence rates in stage III CC patients. However, only microsatellite status seems to be associated with specific recurrence patterns. More than two recurrence sites and recurrence in the peritoneum were associated with poorer SAR.

Prognostic factors in patients treated with second-line chemotherapy for advanced gastric cancer: results from the randomized prospective phase III FFCD-0307 trial.

AIM: The aim of this study was to determine prognostic factors in patients treated with second-line therapy (L2) for locally advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma in a randomized phase III study with predefined L2. METHODS: In the FFCD-0307 study, patients were randomly assigned to receive in L1 either epirubicin, cisplatin, and capecitabine (ECX arm) or fluorouracil, leucovorin, and irinotecan (FOLFIRI arm). L2 treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). Chi square tests were used to compare the characteristics of patients treated in L2 with those of patients who did not receive L2. Prognostic factors in L2 for progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox model. RESULTS: Among 416 patients included, 101/209 (48.3%) patients in the ECX arm received FOLFIRI in L2, and 81/207 (39.1%) patients in the FOLFIRI arm received ECX in L2. Patients treated in L2, compared with those who only received L1 had : a better ECOG score (0-1: 90.4% versus 79.7%; p = 0.0002), more frequent GEJ localization (40.8% versus 27.6%; p = 0.005), and lower platelet count (median: 298000 versus 335000/mm3; p = 0.02). In multivariate analyses, age < 60 years at diagnosis (HR 1.49, 95% CI 1.09-2.03, p = 0.013) and ECOG score 2 before L2 (HR 2.62, 95% CI 1.41-4.84, p = 0.005) were the only significant poor prognostic factors for OS. CONCLUSION: Age ≥ 60 years at diagnosis and ECOG score 0/1 before L2 were the only favorable prognostic factors for OS.

Identification of resources and skills developed by partners of patients with advanced colon cancer: a qualitative study.

PURPOSE: Family caregivers play an important role in caring for patients with advanced cancer. To become competent, individuals must draw on and mobilise an adequate combination of resources. Our goal was to identify the skills developed by caregivers of patients with advanced cancer and the associated resources mobilised. We chose to do it with partners of patients with colon cancer. METHODS: The study used a cross-sectional qualitative design based on 20 individual interviews and a focus group. Partners were recruited from patients treated in three hospitals of France. Semi-structured interviews were conducted until data saturation was achieved. Each interview was transcribed verbatim, and thematic analyses were performed to extract significant themes and subthemes. RESULTS: Results from the individual and focus group interviews showed that the skills implemented by the partners (in domains of social relationships and health, domestic, organisational, emotional and well-being dimensions) were singular constructs, dependant on if resources (personal, external and schemes) may have been missing and insufficient. In addition, partners may have had these resources but not mobilised them. CONCLUSION: The identification of the skills and associated resources could allow healthcare professionals better identifying and understanding of the difficulties met by partners in taking care of patients. This could enable them to offer appropriate support to help the caregivers in their accompaniment.

[Outcomes after a 2-year pharmaceutical care program for patients taking vitamin K antagonist therapy? Community pharmacist's perception]. / Quel bilan à deux ans de la mise en place de l'accompagnement des patients traités par anti-vitamines K ? Le point de vue du pharmacien d'officine.

OBJECTIVES: Since 2013 French community pharmacist are involved in pharmaceutical care program (PCP) for patients treated with vitamin K antagonist (VKA). While PCPs are now extending to other patient populations, we aimed to evaluate pharmacists' perception after 2-years implementation and leading of PCP. METHODS: A prospective investigational survey from 1st August to 31st December, 2015 from 400 community pharmacies in Champagne-Ardenne Region. Survey focuses on 3 points: first about implementation and leading of PCP; secondly about patient's population description; finally on the global perception by CP about new tasks. RESULTS: Among n=47, 72% of pharmacists performed VKA PCP. Almost all received appropriate training (96%). Remuneration appears to be insufficient given the time spent for 73%. Ninety-five percent met patient's refusal mainly because of interest lacking or time lacking (54% and 22%, respectively). Pharmacists reported 3 main lacks of knowledges of patients: drugs, which increase drug-drug interaction risk (28%), VKA overdose effects (27%) and VKA-food interactions (23%). Overall view of pharmacist for PCP appears to be positive (81%) in part because of improvement of pharmacist-patient relationship perception for 66%. CONCLUSIONS: Community pharmacists' perception for PCP for patients treated by VKA is broadly positive. However, organizational or economic constraints can lead to a decreasing adherence by pharmacists to PCPs. A global issue about amount of compensation and communications campaigns to patients and others health professionals will be useful in order to reinforced PCP implementation and leading taxonomy.

Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients.

Background: RAS mutations have been shown to confer resistance to anti- epidermal growth factor receptor (EGFR) treatment. We analysed the results of the PETACC8 trial (cetuximab + FOLFOX vs FOLFOX) in full RAS and BRAF wildtype (WT) patients (pts) with resected stage III colon cancer. Patients and methods: Exons 2, 3 and 4 of KRAS and NRAS, and BRAF exons 11 and 15, were sequenced using the Ampliseq colon-lung cancer panel version 2, in PETACC8 trial pts who consented to translational research. The impact of cetuximab on time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS) was investigated in pts with tumours harbouring RAS and BRAF WT, and RAS mutations. The prognostic value of each individual mutation was also tested. Results: Among the 2559 pts analysed, 745 pts (29%) were known to have KRAS exon 2 mutations and 163 pts (6.4%) the BRAF V600E mutation. Of the remaining 1651 pts, 1054 were assessed by NGS, showing that a further 227 pts (21%) had KRAS exon 2, 3, 4 or NRAS exon 2, 3, 4 mutations, and that 46 pts (4.4%) had a newly diagnosed BRAF mutation. Cetuximab added to FOLFOX did not significantly improve TTR, DFS or OS in pts with RAS WT or RAS and BRAF WT tumours (HR 0.77-1.03, all P > 0.05). Cetuximab addition was not either significantly deleterious in RAS mutant pts or in pts with rare RAS or BRAF mutations. In the overall trial population, NRAS and KRAS codon 61 mutations were the only rare mutations with the same pejorative prognostic value as KRAS exon 2 or BRAF V600E mutations. Conclusion: Though not significant, the clinically relevant 0.76 adjusted HR observed for DFS in favour of adding cetuximab to FOLFOX, in full RAS and BRAF WT stage III colon cancer pts, may justify a new randomized controlled trial testing EGFR inhibitors in this setting. Clinical trial number: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

[Benefits of volumetric to facial rejuvenation. Part 1: Fat grafting]. / Apport de la volumétrie au rajeunissement facial. Partie 1 : greffe adipocytaire.

For a number of years, a volumetric approach using autologous fat injection has been implemented to improve cosmetic outcome in face-lift procedures and to achieve lasting rejuvenation. Autologous fat as filling tissue has been used in plastic surgery since the late 19th century, but has only recently been associated to face lift procedures. The interest of the association lies on the one hand in the pathophysiology of facial aging, involving skin sag and loss of volume, and on the other hand in the tissue induction properties of grafted fat, "rejuvenating" the injected area. The strict methodology consisting in harvesting, treating then injecting an autologous fat graft is known as LipoStructure® or lipofilling. We here describe the technique overall, then region by region. It is now well known and seems simple, effective and reproducible, but is nevertheless delicate. For each individual, it is necessary to restore a harmonious face with well-distributed volumes. By associating volumetric to the face lift procedure, the plastic surgeon plays a new role: instead of being a tailor, cutting away excess skin, he or she becomes a sculptor, remodeling the face to restore the harmony of youth.

[Benefits of volumetric to facial rejuvenation. Part 2: Dermal fillers]. / Apport de la volumétrie au rajeunissement facial. Partie 2 : produits de comblement.

Injectable substances known as fillers are used to palliate age-related atrophy and ptosis, and for their so-called "pseudo-lifting" action. They do not replace face and neck lift, but allow it to be postponed or, when injected after surgical lifting, make the result durable. Hyaluronic acid has a predominant and unchallenged place among fillers, well ahead of poly-L-lactic acid or calcium hydroxyapatite. Approaches and injection methods are the same for all fillers, corresponding to those for autologous fat injection, the reference substance, with a few particularities. The substance used, the level of hyaluronic acid reticulation, and the depth of the injection depend on the injection site and intended effect. Effects range from smoothing superficial wrinkles to remodeling whole parts of the face. Complications related to such fillers are well known, especially in the case of hyaluronic acid, where overcorrection is the most frequent. To limit the risk of complications and also to offer each patient the most individually adapted corrections, before any procedure, the plastic surgeon needs to question the patient and perform precise medical examination.

Childhood cognitive ability accounts for associations between cognitive ability and brain cortical thickness in old age.

Associations between brain cortical tissue volume and cognitive function in old age are frequently interpreted as suggesting that preservation of cortical tissue is the foundation of successful cognitive aging. However, this association could also, in part, reflect a lifelong association between cognitive ability and cortical tissue. We analyzed data on 588 subjects from the Lothian Birth Cohort 1936 who had intelligence quotient (IQ) scores from the same cognitive test available at both 11 and 70 years of age as well as high-resolution brain magnetic resonance imaging data obtained at approximately 73 years of age. Cortical thickness was estimated at 81 924 sampling points across the cortex for each subject using an automated pipeline. Multiple regression was used to assess associations between cortical thickness and the IQ measures at 11 and 70 years. Childhood IQ accounted for more than two-third of the association between IQ at 70 years and cortical thickness measured at age 73 years. This warns against ascribing a causal interpretation to the association between cognitive ability and cortical tissue in old age based on assumptions about, and exclusive reference to, the aging process and any associated disease. Without early-life measures of cognitive ability, it would have been tempting to conclude that preservation of cortical thickness in old age is a foundation for successful cognitive aging when, instead, it is a lifelong association. This being said, results should not be construed as meaning that all studies on aging require direct measures of childhood IQ, but as suggesting that proxy measures of prior cognitive function can be useful to take into consideration.

Epidemiology, Management, and Survival of Peritoneal Carcinomatosis from Colorectal Cancer: A Population-Based Study.

BACKGROUND: Modern chemotherapy aims to improve long-term survival for selected patients with peritoneal carcinomatosis. Publications suggest promising results, but the spread of these new aggressive treatment strategies in the general population is not well known. OBJECTIVE: The aim of this study was to draw a picture of epidemiology, management, and survival in synchronous and metachronous peritoneal carcinomatosis from colorectal cancer. DESIGN: The cumulative risk of metachronous peritoneal carcinomatosis was estimated in patients resected for cure. Net survival rates were calculated for synchronous and metachronous peritoneal carcinomatosis. SETTINGS: The study was conducted with the use of the Burgundy Digestive Cancer Registry. PATIENTS: Overall, 9174 primary colorectal cancers registered between 1976 and 2011 by the population-based digestive cancer registry were considered. RESULTS: In total, 7% of patients were diagnosed with synchronous peritoneal carcinomatosis. The 5-year cumulative risk of metachronous peritoneal carcinomatosis was 6%, and the stage of the colorectal cancer at diagnosis was the major risk factor. Other independent risk factors were mucinous adenocarcinoma, ulceroinfiltrating tumors, and diagnosis after obstruction or perforation. The proportion of patients resected for cure was 11% and 9% for synchronous and metachronous peritoneal carcinomatosis, and 3-year overall net survival was 8% and 5%. The corresponding rates after resection for cure were 21% and 17%. There was a dramatic increase in the proportion of patients receiving systemic chemotherapy: from 11% before 1997 to 48% in 2011 for synchronous peritoneal carcinomatosis and from 3% to 38% for metachronous peritoneal carcinomatosis. LIMITATIONS: This is a retrospective observational population-based study. CONCLUSION: Peritoneal carcinomatosis complicating colorectal cancer is a major reason for treatment failure. This study identified patients at a high risk of developing peritoneal carcinomatosis who may benefit from specific surveillance. New therapeutic modalities are also needed to improve the prognosis.

Clinical and economic impact of drug eluting beads in transarterial chemoembolization for hepatocellular carcinoma.

WHAT IS KNOWN AND OBJECTIVE: Drug eluting beads (DEBs) theoretically improve the efficacy and safety of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Nonetheless, their economic profile has not been assessed. Our retrospective before/after study aimed to compare efficacy, safety and economic profile of two strategies of TACE without (Period 1) or with the possibility of using DEBs (Period 2). METHODS: All HCC patients treated by TACE in our hospital between March 2006 and May 2013 were included. Economic analyses were performed from the French Public Health Insurance point of view according to the French Diagnosis-Related Group prospective payment system and from the analytic accountability. RESULTS AND DISCUSSION: One hundred and sixty-one patients were included. Median time to treatment failure and overall survival were 13.1 and 23.8 months in Period 1 vs. 14.1 and 30.2 months in Period 2 (P = 0.45 and P = 0.40). Mean hospital durations and tariffs were 14.9 ± 7.7 days and € 11 472 ± 5901 in Period 1 vs. 12.4 ± 8.4 days and € 7654 ± 4625 in Period 2 (P = 0.03 and P < 10(-4) ). WHAT IS NEW AND CONCLUSION: The possibility of using DEBs did not improve the prognosis in HCC patients treated by TACE. Nonetheless, it had a better medico-economic profile.

[Setting of a breast autologous microsurgical reconstructive surgery evolution in 20 years and review of 1138 cases]. / Mise en place d'une activité de reconstruction microchirurgicale du sein par tissus autologues. Évolution sur 20 ans et revue de 1138 cas.

UNLABELLED: The authors conducted a retrospective study of breast reconstruction with DIEP free flap between 1994 and 2014 by a single team. MATERIAL AND METHOD: A retrospective analysis of all operative charts and hospitalization was conducted for the period from 1994 to 2014. The number of cases per year, the complication rate of the donor site and recipient site, and surgery time were recorded. Sequence analysis was conducted to determine the elements that have enabled to implement this technique reliably and effects of the learning curve. The series was split into two periods (1994/2011 and 2012/2014) corresponding to two different hospitals with the same team. RESULTS: The total number of shreds of 1138 between November 1994 and December 2014 respectively with 477 and 661 the period 1994/2011 to 2012/2014 period. The failure rate increased from 8% to 2.2%. CONCLUSION: The establishment of units mainly dedicated to microsurgical reconstruction can offer the DIEP technique reliably and reproducibly.

Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset.

BACKGROUND: The prognostic value of KRAS mutations in colon adenocarcinoma is controversial. We examined this question as an ancillary study of the PETACC8 phase III trial. PATIENTS AND METHODS: We analyzed the prognostic impact of KRAS exon 2 mutations in stage III colon cancer patients (n = 1657) receiving adjuvant FOLFOX ± cetuximab therapy included in the PETACC8 trial. Patients with BRAF-mutated cancers were excluded and, as no difference was found for time to recurrence (TTR) and disease-free survival (DFS) between treatment arms, both were pooled for analysis. Associations with TTR and DFS were analyzed using a Cox proportional hazards model. RESULTS: KRAS mutations were found in 638 of 1657 tumors and linked to shorter TTR (P < 0.001). However, when specific mutations were compared with wild-type, codon 12 mutations [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.35-2.04; P < 0.001] but not codon 13 (HR 1.23, 95% CI 0.85-1.79; P = 0.26) were significantly associated with shorter TTR, independently of other covariates. The interaction test showed that, regarding tumor location (distal versus proximal), KRAS genotype affects differently on recurrence (P = 0.02) and DFS (P = 0.042). Subgroup analysis showed that KRAS only affected TTR and DFS in distal tumors (n = 1043; 692 wild type; 351 mutated), with an increased risk of relapse (HR 1.96, 95% CI 1.51-2.56; P < 0.0001) for KRAS codon 12 mutations and a borderline significance for codon 13 mutations (HR 1.59, 95% CI 1.00-2.56; P = 0.051). CONCLUSION: KRAS exon 2 mutations are independent predictors of shorter TTR in patients with resected stage III distal colon cancers receiving adjuvant therapy. Future clinical trials in the adjuvant setting should consider both the tumor location and KRAS mutations as important stratification factors. CLINICAL TRIAL NUMBER: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

Long-term net survival in patients with colorectal cancer in France: an informative contribution of recent methodology.

BACKGROUND: Net survival, the survival that might occur if cancer was the only cause of death, is a major epidemiological indicator. Recent findings have shown that the classical methods used for the estimation of net survival from cancer registry data, referred as to "relative-survival methods," provided biased estimates. OBJECTIVES: The aim of this study was to provide, for the first time, long-term net survival rates for colorectal cancer by using a population-based digestive cancer registry. DESIGN: This study is a population-based cancer registry analysis. The recently proposed unbiased nonparametric Pohar-Perme estimator was used. PATIENTS: Overall, 14,715 colorectal cancers diagnosed between 1976 and 2005 and registered in the population-based digestive cancer registry of Burgundy (France) were included. MAIN OUTCOME MEASURES: The primary outcome measured was cancer net survival, ie, the survival that might occur if all risks of dying of other causes than cancer were removed RESULTS: : Ten-year net survival increased from 31% during the 1976 to 1985 period to 47% during the 1986 to 1995 period and then leveled out (48% during the 1996-2005 period). There was a major improvement in 10-year net survival after resection for cure and for stage I to III. It was striking for stage III cancers, for which 10-year net survival increased from 21% (1976-1985) to 49% (1996-2005). The corresponding net survivals were 70% and 87% for stage I and 49% and 65% for stage II. These trends can be related to the decrease in operative mortality, the increase in the proportion of patients resected for cure, and the improvement in stage at diagnosis. They were mainly seen between 1976 and 1995, explaining why survival leveled out after 1995. LIMITATIONS: The study was limited by its retrospective and population-based nature. CONCLUSIONS: Further improvements for colorectal cancer management can be expected from more effective treatments and from the implementation of organized cancer screening.

Patterns of recurrence of obstructing colon cancers after surgery for cure: a population-based study.

AIM: Little is known about patterns of recurrence in obstructing colon cancer (OCC) at a population level. The aim of this study was to determine the risk of recurrence following potentially curative surgery in OCC compared with that in uncomplicated colon cancer (CC). METHOD: Data were obtained from the population-based digestive cancer registry of Burgundy (France). Local and distant failure rates were calculated using actuarial methods. A multivariate analysis was performed using a Cox model. RESULTS: Obstructing colon cancer represented 8.5% of all colon cancers resected with curative intent (n = 3375). The 5-year cumulative local recurrence rate was 14.2% for OCC and 7.6% for nonobstructing CC (P = 0.003). In the multivariate analysis, obstruction was an independent risk factor for local recurrence [hazard ratio 1.53 (1.01-2.34), P = 0.047]. The risk of local recurrence increased with advanced stage and age at diagnosis. The 5-year cumulative rate for distant metastases was also higher in OCC than in nonobstructing CC (36.1 vs 23.1%; P < 0.001). The relative risk of distant metastasis was borderline significant in the multivariate analysis [hazard ratio 1.25 (0.99-1.59), P = 0.057]. Stage at diagnosis, macroscopic type of growth, period of diagnosis and sex were also significant prognostic factors. Age and subsite were not significant in the multivariate analysis. CONCLUSION: It is possible to conduct special surveys in population-based registries to determine the recurrence rate of CC. Recurrence remains a substantial problem and is more frequent in OCC than in nonobstructing CC. Efforts must be made to diagnose CC earlier. Mass screening is a promising approach.

[Fibrin sealant significantly decrease postoperative drainage in breast reconstruction by deep inferior epigastric perforator (DIEP) flap]. / Diminution significative des volumes de drainage postopératoires en reconstruction mammaire différée par lambeau libre DIEP par utilisation de colle de fibrine.

PURPOSE: Serosanguinous drainage after breast reconstruction by deep inferior epigastric perforator (DIEP) flap constitute with the microsurgical monitoring, the main limiting factors for patient discharge. Fibrin sealant has already been studied to reduce post breast surgery drainage. The authors are presenting their experience in secondary breast reconstruction by DIEP flap with the use of sprayed fibrin sealant. PATIENTS AND METHODS: Twenty-one female patients aged 28 to 63 years old who underwent secondary breast reconstruction after mastectomy for cancer between October 2004 and June 2007 have been reviewed. These patients were separated into two groups. In group 1, patients (n=9) received two drains placed under the flap and in the axillary area. In group 2, (n=12) the DIEP flaps and thoracic areas were sprayed with fibrin sealant (Tissucol(®)) before the two drains inset. RESULTS: No adverse effect were reported, with a 36-month median follow-up. Drainages volumes or durations were not correlated to the patients' Body Mass Index (BMI). Lower drained volumes were collected from the thoracic region (372ml versus 629mL) and thoracic drains were removed earlier (5.5 days versus 6.9 days) in group 2. The length of stay was also significantly reduced after fibrin sealant use (5.5 days versus 7.22 days with P=0.0305 by log rank test). CONCLUSION: This study is a rare clinical one on fibrin sealant use to decrease postoperative drainage in breast reconstruction by DIEP flap. Fibrin sealant significantly decreased the postoperative drainage volume and duration.

[A cost analysis of DIEP flap in breast reconstruction]. / Analyse médico-économique du lambeau libre de DIEP en reconstruction mammaire.

BACKGROUND: We postulate that the absence of a CPT code for DIEP (deep inferior epigastric perforator) free flap in breast reconstruction is in part responsible for the delayed adoption of this modern technique in France. In order to provide data to our regulating health agency, we determined the cost of this technique compared to a gold standard. We performed a cost-identification study, comparing costs of DIEP free flap versus latissimus dorsi pedicled flap with implant (LD+I) in secondary breast reconstruction following irradiation. METHODS: Over a 12-month period, direct medical and non-medical costs as well as indirect costs were recorded in both groups (DIEP and LD+I). RESULTS: In an academic department funded by the national health system, total cost of a secondary breast reconstruction by DIEP free flap was 10,671 ± 3005€ (n=57) versus 8218 ± 2049€ (n=18) for the LD+I group (P<0.05). Mean OR occupation time was 390 ± 64minutes for DIEP versus 283 ± 44minutes for LD+I (P<0.05). Mean hospital stay was 6 ± 2 days for DIEP versus 5 ± 2 days for LD+I (P>0.05). CONCLUSION: DIEP free flap technique offers a long lasting breast reconstruction at an reasonable expense compared to the LD+I (+22%). Furthermore, in an academic department, collaboration of two microsurgeons during DIEP flaps allows OR times to drop significantly and become competitive with LD+I.

European disparities in malignant digestive endocrine tumours survival.

The aim of this study was to report on malignant digestive endocrine tumours (MDET) prognosis in several European countries. We analysed survival data from 19 cancer registries in 12 European countries on 3,715 MDET diagnosed between 1985 and 1994. The overall 5-year survival rate was 47.5%. It was 58.1% for differentiated MDET and 8.1% for small-cell MDET (p < 0.001), 55.9% for patients under 65 and 37.0% for older patients. Survival rates for small intestinal and colorectal were higher than for the other sites. The 5-year relative survival rates were 60.3% in Northern Europe, 53.6% in Western Continental Europe, 42.5% in the UK, 37.6% in Eastern Europe (p < 0.001). Among well-differentiated pancreatic tumours, 5-year relative survival was 55.6% for insulinoma, 48.4% for gastrinoma, 33.4% for glucagonoma, 28.8% for carcinoid tumours and 49.9% for non-functioning tumours. The relative excess risk of death was significantly lower in Western Continental Europe and Northern Europe and significantly higher in Easter European compared to the UK. MDET differentiation, site, geographic area, age and sex, were independent prognostic factors. Overall, in Europe approximately half of the patients with MDET survive 5 years after the initial diagnosis. Prognosis varies with tumour differentiation, anatomic site and histological type. There are significant differences in survival from MDET among European countries, independently of other prognostic factors.

Operative mortality after gastric cancer resection and long-term survival differences across Europe.

BACKGROUND: : Little is known at a population level about operative mortality after surgery for gastric cancer and whether differences between countries can explain differences in long-term survival. This study compared operative mortality recorded by ten cancer registries in seven European countries. METHODS: : Non-conditional logistic regression analysis was performed to estimate the independent effect of the studied factors on mortality within 30 days of surgery. A multivariable survival model was employed with and without operative mortality. RESULTS: : The overall operative mortality rate in 1611 patients studied was 8.9 (range 5.2-16) per cent. Country of residence was a significant prognostic factor in the multivariable analysis. The likelihood of operative mortality was lower in Italy, France and the UK than in the Netherlands, Spain, Slovenia and Poland. Age, type of gastrectomy and stage at diagnosis were also significant factors. Cancer site was not found to be significant in the multivariable analysis. The overall 5-year relative survival rate varied between 42.0 per cent (Italy) and 24 per cent (Poland); after excluding operative mortality, the 5-year survival rate was 44.3 and 28 per cent respectively. CONCLUSION: : Within Europe, the substantial differences in operative mortality after gastrectomy only partly explain marked differences in survival after gastric cancer resection.

Loss of SMARCB1 expression in colon carcinoma.

SMARCB1 is a tumor suppressor gene, which is part of SWI/SNF complex involved in transcriptional regulation. Recently, loss of SMARCB1 expression has been reported in gastrointestinal carcinomas. Our purpose was to evaluate the incidence and prognostic value of SMARCB1 loss in colon carcinoma (CC). Patients with stage III CC (n= 1695), and a second cohort of 23 patients with poorly differentiated CC were analyzed. Immunohistochemistry for SMARCB1 was performed on tissue microarrays, and cases with loss of expression were controlled on whole sections. Loss of SMARCB1 was compared with the clinico-pathological and molecular characteristics, and the prognostic value was evaluated. Loss of SMARCB1 was identified in 12 of 1695 (0.7%) patients with stage III CC. Whole section controls showed a complete loss in only one of these cases, corresponding to a medullary carcinoma. SMARCB1 loss was not associated with histological grade, tumor size nor survival. In the cohort of poorly differentiated CC, we detected 2/23 (8.7%) cases with loss of SMARCB1; one was rhabdoid while the other had medullary and mucinous histology. These 2 cases were deficient for MisMatched Repair (dMMR) and mutated for BRAF. SMARCB1 loss is rare in stage III CC, but appears more frequent in poorly differentiated CC.