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The aim of this paper was to review the entire literature on esophageal surgery to best define the surgical indications and the specifics of their management. The bibliographic research was carried out on Pubmed between January 1995 and June 2015, using French and English as publication languages.

International audience; Secreted mucins are large O-glycosylated proteins that participate in the protection/defence of underlying mucosae in normal adults. Alteration of their expression is a hallmark of numerous epithelial cancers and has often been correlated to bad prognosis of the tumour. The secreted mucin MUC5B is overexpressed in certain subtypes of gastric and intestinal cancers, but the consequences of this altered expression on the cancer cell behaviour are not known. To investigate the role of MUC5B in carcinogenesis, its expression was knocked-down in the human gastric cancer cell line KATO-III and in the colonic cancer cell line LS174T by using transient and stable approaches. Consequences of MUC5B knocking-down on cancer cells were studied with respect to in vitro proliferation, migration and invasion, and in vivo on tumour growth using a mouse subcutaneous xenograft model. Western blotting, luciferase assay and qRT-PCR were used to identify proteins and signalling pathways involved. In vitro MUC5B down-regulation leads to a decrease in proliferation, migration and invasion properties in both cell lines. Molecular mechanisms involved the alteration of β-catenin expression, localization and activity and decreased expression of several of its target genes. In vivo xenografts of MUC5B-deficient cells induced a decrease in tumour growth when compared with MUC5B-expressing Mock cells. Altogether, the present study shows that down-regulation of MUC5B profoundly alters proliferation, migration and invasion of human gastrointestinal cancer cells and that these alterations may be, in part, mediated by the Wnt/β-catenin pathway emphasizing the potential of MUC5B as an actor of gastrointestinal carcinogenesis.

Anastomotic leakage following total gastrectomy or esophagectomy is a significant complication that considerably increases postoperative mortality. The location of the anastomosis together with the anatomy of the esophagus explains the severity of this complication. Surgical knowledge should include general and specific predictive factors of leakage to avoid any technical-related cause of leakage. Clinical presentations may vary from minimally symptomatic to life-threatening situations. Investigations should be undertaken as soon as the diagnosis is suspected because delay greatly worsens the prognosis. CT scans with oral contrast and low insufflation early endoscopy are the preferred diagnostic tools and can also aid in therapeutic procedures. Communication and multidisciplinary teamwork are the cornerstones of treatment. When the leak occurs early with acute and important sepsis, the recommendation is surgical treatment. On the contrary, if the leak is late, non-symptomatic or minimally symptomatic, conservative management with intensive surveillance could be proposed. When the situation is in between these two extremes, endoscopic treatment is often proposed. Based on a review of the literature and experience from high volume centers, in this educational review, we present the incidence, predictive factors, clinical presentations, diagnostic tools, management, and therapeutic algorithms for anastomotic leaks following elective esophagectomy and total gastrectomy for cancer.

Background Even though the perioperative chemotherapy improves the overall survival (OS) compared to surgery alone in patients with a resectable gastroesophageal adenocarcinoma (GEA), prognosis of these patients remains poor. Docetaxel (D), cisplatin (C), and 5-fluorouracil (F) regimen improves OS compared to CF among patients with advanced GEA. We evaluated the potential interest of a perioperative DCF regimen, compared to standard (S) regimens, in resectable GEA patients. Methods We identified 459 patients treated with preoperative DCF or S regimens. The primary endpoint was OS. Propensity scores were estimated with a logistic regression model in which all baseline covariates were included. We then used two methods to take PS into account and thus make DCF and S patients comparable. OS analyses were performed with Kaplan–Meier and Cox models in propensity score matched samples, and inverse probability of treatment weighted (IPTW) samples. Results In the propensity score matched sample, the p-value from the log rank test for OS was 0.0961, and the 3-year OS rate was 73% and 55% in DCF and S groups, respectively. The multivariate Cox regression underlined a Hazard Ratio of 0.55 (95% CI 0.27–1.13) for DCF patients compared to S patients. The results from IPTW analyses showed that DCF was significantly and independently associated with OS (HR = 0.52; 95% CI 0.40–0.69). Conclusions In this retrospective multicenter, hypothesis-generating study, the propensity score analyses underlined encouraging results in favor of DCF compared to S regimens regarding OS. This promising result should be validated in a phase-3 trial.

Docetaxel, cisplatin, and 5‐fluorouracil (DCF) significantly improved overall survival in metastatic gastroesophageal adenocarcinoma (GEA). The aim of this study was to assess efficacy of DCF regimen as perioperative chemotherapy compared with surgery alone in patients with resectable GEA. We identified 789 patients who underwent surgery alone and 62 patients who received at least one cycle of DCF regimen consisting of docetaxel (75 mg/m2 on day 1), cisplatin (75 mg/m2 on day 1), and 5‐fluorouracil (750 mg/m2/day on continuous perfusion on days 1 to 5), every 3 weeks. Overall survival was compared using Cox proportional hazards regression model with adjustments for confounding factors provided by two propensity score methods: inverse probability of treatment weighting (IPTW) and matched‐pair analysis. In Cox multivariate analysis weighted by IPTW, DCF group was associated with favorable overall survival (OS) compared with the surgery group (HR = 0.59; 95% CI, 0.45–0.78; P = 0.0003). For the matched‐pair analysis (comparing 41 patients for each group with the same baseline characteristics), median OS was 22 months and 57 months for the surgery group and DCF group, respectively (log‐rank P = 0.0011). In Cox multivariate analysis, DCF group was associated with favorable OS compared with the surgery group (HR = 0.29; 95% IC, 0.14–0.64; P = 0.0019). In the matched‐pair population, major complications (Dindo‐Clavien grade 3–5) arose in six patients (14.63%) in the DCF group and seven patients (17.07%) in the surgery group (P = 1). Perioperative DCF chemotherapy is superior to surgery alone in terms of OS. A randomized phase III trial should compare DCF to standard perioperative regimens.

Extensive surgery is associated with greater mortality for elderly patients. For gastric adenocarcinoma (GA), it is unclear whether the benefit of an extended lymphadenectomy in this population outweighs the associated risks. This study aimed to determine the impact of lymphadenectomy on postoperative outcomes and survival for the elderly.To determine the impact of lymphadenectomy on postoperative outcomes and survival for elderly.From a cohort of 19 centers, patients who underwent resection of GA with curative intent between 1997 and 2010 were included in this study. Lymphadenectomy was defined according to the total number of lymph nodes in the surgical specimen (limited, 15; intermediate, 15-25; extended, 25). Postoperative outcomes and survival were compared between elderly (≥75 years) and younger patients and regarding the extent of lymphadenectomy for the elderly.Of 1348 patients, 386 were elderly. The elderly presented with a higher American Society of Anesthesiologist (ASA) score (ASA 3-4: 45 vs. 16.5 %; p 0.001) as well as greater postoperative morbidity (45 vs. 37 %; p = 0.009) and mortality (8 vs. 2.5 %; p 0.001) despite less aggressive treatment including less neoadjuvant chemotherapy (5 vs. 20 %; p 0.001) and adjuvant chemotherapy (7 vs. 44 %; p 0.001), fewer total gastrectomies (41.5 vs. 60 %; p 0.001), and less extended lymphadenectomy (38 vs. 48.5 %; p 0.001). Among the elderly patients, limited lymphadenectomy (n = 116), intermediate lymphadenectomy (n = 125), and extended lymphadenectomy (n = 145) were comparable with respect to tumor stage, perioperative treatment, morbidity, and mortality. For the elderly patients, overall survival (OS) was 30.8 months, and disease-specific survival (DSS) was 63.9 months. The extent of the lymphadenectomy did not have an impact on OS or DSS for the elderly patients.The expected benefit in terms of long-term survival did not justify an extended lymphadenectomy for elderly patients.

Total pancreatectomy with intraportal islet autotransplantation (TPIAT) rather than partial pancreatectomy could represent a major shift in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC) when risks of postoperative pancreatic fistula are well identified. This approach provides a theoretical risk of tumor cell dissemination when islet cells are transplanted into the portal vein. Our objective was to explore the safety of TPIAT in PDAC in a mouse preclinical model of subcutaneous xenotransplantation of human cells isolated from pancreatic specimen during partial pancreatectomy performed for PDAC.Patients requiring pancreatectomy for PDAC were prospectively included. Immunocompromised mice were transplanted with pancreatic cells isolated from the nonmalignant part of the surgical specimen (experimental group). Results were compared with pancreatic tumor implants (control group). Pancreatic grafts were explanted at 6 weeks for histological analyses.Nine patients were included, and 31 mice were transplanted. In the experimental group, explants were microscopically devoid of tumor cell, and no metastasis was observed. In the control group, all explants were composed of tumor.We report in a preclinical model the absence of local and distant spreading of malignant cells after pancreatic islets xenograft isolated from PDAC patients. These data supports the oncological safety of TPIAT as valuable alternative to partial pancreatectomy for PDAC patients with a high risk of postoperative pancreatic fistula.

The prognosis and chemoresistance of signet-ring cell (SRC) gastric adenocarcinoma have been reported and debated, and the utility of perioperative chemotherapy for such a tumor has been questioned . This study was performed to assess the impact of the SRC type on survival following resection of gastric adenocarcinoma, and to assess whether the prognostic factors (including perioperative chemotherapy) for non-SRC adenocarcinoma differed from those for SRC adenocarcinoma.1799 cases of adenocarcinoma that were consecutively treated from 1997 to 2010 in 19 French centers by subtotal or total gastrectomy were included in a retrospective study. A D2 lymphadenectomy was performed for antropyloric tumors, and a modified D2 for upper tumors. SRC adenocarcinoma was diagnosed based on the presence of isolated carcinoma cells containing mucin.A total gastrectomy was performed in 979 (54.4 %) patients. SRC adenocarcinoma was diagnosed in 899 (50 %) patients. Patients with an SRC tumor were more frequently female, younger, and malnourished, had lower ASA scores, and had larger tumors than non-SRC patients. Median survival in patients with non-SRC carcinoma was 51 months, as compared to 26 months in patients with SRC carcinoma (p 0.001). At multivariate analysis, SRC type remained an independent adverse prognostic factor (HR = 1.182). Factors that were prognostic in the SRC subgroup but not in the non-SRC subgroup were age60 years, linitis, and involvement of adjacent organs. In contrast to non-SRC tumors, pre- and postoperative chemotherapy did not significantly impact on survival following resection of SRC adenocarcinoma.In comparison to non-SRC adenocarcinoma, the SRC type has a worse prognosis, different prognostic factors, and is only poorly sensitive to perioperative chemotherapy. Non-SRC and SRC adenocarcinomas should be considered different entities in future therapeutic trials.

Background Patterns of disease recurrence in patients with oesophageal cancer following treatment with neoadjuvant chemoradiotherapy and surgery (nCRTS) or surgery alone are poorly reported. An understanding of patterns of disease recurrence is important for subsequent treatment planning. Methods An analysis was undertaken of patterns of disease recurrence from a phase III multicentre randomized trial (FFCD9901) comparing nCRTS with surgery alone in patients with stage I and II oesophageal cancer. Results Some 170 patients undergoing surgical resection were included in the study. R0 resection rates were similar in the two groups: 94 per cent following nCRTSversus 92 per cent after surgery alone (P = 0·749). After a median follow-up of 94·2 months, recurrent disease was found in 39·4 per cent of the overall cohort (31 per cent after nCRTSversus 47 per cent following surgery alone; P = 0·030). Locoregional recurrence was diagnosed in 41 patients (17 versus 30 per cent respectively; P = 0·047) and distant metastatic recurrence in 47 (23 versus 31 per cent respectively; P = 0·244). Metastatic recurrence was more frequent in patients with adenocarcinoma than in those with squamous cell cancer (40 versus 23·1 per cent respectively; P = 0·032). ypT0 N0 category was associated with prolonged time to mixed locoregional and metastatic recurrence (P = 0·009), and time to locoregional (P = 0·044) and metastatic (P = 0·055) recurrence. In multivariable analysis, node-positive disease predicted both locoregional (P = 0·001) and metastatic (P < 0·001) recurrence. Conclusion Locoregional disease control following nCRTS indicated a local field effect not related solely to completeness of resection. pN+ disease was strongly predictive of time to locoregional and metastatic disease recurrence.

Resume La fistule anastomotique est une complication majeure en chirurgie digestive, responsable d’une augmentation de la morbidite postoperatoire, et premiere cause de mortalite apres chirurgie d’exerese. L’identification des facteurs de risque est un prerequis indispensable a la prevention de la fistule. La fistule peut se manifester par differents tableaux cliniques, allant de l’absence de symptomes, au choc septique avec mise en jeu du pronostic vital. Le scanner injecte avec opacification est l’examen le plus exhaustif pour l’exploration de tout type de fistule et de ses repercussions. Un diagnostic precoce et une prise en charge optimale multidisciplinaire de la fistule permettent de diminuer la morbi-mortalite postoperatoire. Elle est basee sur trois options : medicale, interventionnelle de type radiologique ou endoscopique, ou chirurgicale, dont le choix depend de l’etat septique du malade. Si le patient est asymptomatique, le traitement peut etre exclusivement medical avec une surveillance rapprochee. Un traitement interventionnel est entrepris pour une fistule symptomatique si le pronostic vital n’est pas engage. Si par contre le pronostic vital est mis en jeu, une reintervention chirurgicale en urgence est necessaire, associee a une reanimation intensive. Plus que leur prevention, c’est la precocite et la qualite de la prise en charge des fistules anastomotiques qui en diminuent leur retentissement.

Anastomotic leakage represents a major complication of gastrointestinal surgery, leading to increased postoperative morbidity; it the foremost cause of mortality after intestinal resection. Identification of risk factors is essential for the prevention of AL. AL can present with various clinical pictures, ranging from the absence of symptoms to life-threatening septic shock. Contrast-enhanced CT scan is the most complete investigation to define AL and its consequences. Early and optimal multidisciplinary management is based on three options: medical management, radiologic or endoscopic intervention, or surgical re-intervention. Prompt treatment should help decrease postoperative morbidity and mortality, with the choice depending on the septic status of the patient. If the patient is asymptomatic, treatment can be medical only, coupled with close surveillance. Interventional management is indicated when the fistula is symptomatic but not life-threatening. On the other hand, when the vital prognosis is engaged, surgery is indicated, emergently, associated with intensive care. Even more than their prevention, early and appropriate management counts most to decrease their consequences.

Signet ring cell (SRC) tumors have a worse prognosis when compared with non-SRC tumors, and neoadjuvant chemotherapy has been suggested to be an ineffective treatment strategy. Preoperative radiochemotherapy, of already proven efficacy for esophagogastric junction adenocarcinomas (EGJA), could be an alternative neoadjuvant strategy for SRC EGJA. The aim of this retrospective study was to evaluate the survival impact of preoperative radiochemotherapy on patients with advanced resectable SRC EGJA.Of 3,010 patients registered in 21 French centers between January 1997 and January 2010, 2,670 underwent surgical resection, of whom 97 patients had a stage III SRC EGJA treated by either neoadjuvant radiochemotherapy followed by surgery (group RCT, n = 23) or primary surgery (group S, n = 74).Groups were comparable by age, sex, American Society of Anesthesiologists score, malnutrition, and cTNM stage. There was evidence of significant tumoral (p = 0.003), nodal (p0.001), and pTNM (p0.001) downstaging after radiochemotherapy. In group RCT and group S, 3-year overall survival was 51% and 21% (p = 0.002), respectively, with disease recurrence rate of 30.4% versus 59.5% (p = 0.015), respectively. In multivariate analysis the sole independent favorable prognostic factor identified was the administration of neoadjuvant radiochemotherapy (hazard ratio 0.41, p = 0.020).In the setting of locally advanced SRC EGJA, neoadjuvant radiochemotherapy is responsible for tumoral downstaging, reduced disease recurrence, and improved patient survival. A strategy of preoperative radiochemotherapy should be implemented in clinical practice to treat advanced SRC EGJA.

Objective To compare the outcomes of a strategy of surveillance versus surgical resection in patients with esophageal cancer (EC) experiencing complete clinical response (cCR) after chemoradiation (CRT). Background In EC, it remains unclear whether a strategy of surveillance or esophagectomy is appropriate after cCR to CRT. Methods From 1995 to 2009, 222 operable patients had a cCR based on the results of a computed tomographic scan, endoscopy with biopsies and, when performed, a positron emission tomographic scan. Through an intention-to-treat case-control study, 59 patients treated with CRT and surveillance (group Surv) were matched 1:2 with 118 patients treated by CRT followed by surgery (group Surg), according to age, gender, tumor location and stage, histology, American Society of Anesthesiologists score, and nutritional status. Results The 2 groups were comparable according to the matched variables (P > 0.276). In group Surg, the postoperative mortality rate was 4.2% with evidence of residual tumor in 34.6% of specimens. In group Surv, 2 salvage esophagectomies were performed. Despite the higher dose of radiotherapy received in group Surv (50 vs 45 Gys, P = 0.003), median survival was lower (31 vs 83 months, P = 0.001), with disease recurrence that was more frequent (50.8% vs 32.7%, P = 0.021), occurred earlier (7.8 vs 19.0 months, P = 0.002) and more often locoregional (46.7% vs 16.2%, P = 0.007) in nature. Surgical resection was independently associated with less recurrence [odds ratio = 0.4, 95% confidence interval (CI): 0.2-0.8, P = 0.006] and better survival (hazard ratio = 0.5, 95% CI: 0.3-0.8, P = 0.006). Conclusions Survival of EC patients with a cCR after CRT is better after surgery compared to simply surveillance. In patients of low operative risk and operable disease, surgery should be considered to improve control of locoregional disease and to overcome the inherent limitations of clinical response assessment.

RESUME Introduction Alors que le sous-type histologique adenocarcinome a cellules independantes (ADCI) est etabli comme facteur de mauvais pronostic des formes avancees de cancer gastrique, sa valeur pronostique dans les formes superficielles est discutee. Le but de l’etude etait donc de tester l’hypothese du pronostic plus sombre des formes superficielles d’ADCI comparativement aux tumeurs adenocarcinomateuses superficielles non a cellules independantes (NADCI). Patients et methodes A partir d’une cohorte retrospective nationale ayant enregistre tous les cas d’adenocarcinome gastrique operes entre janvier 1997 et janvier 2010 (n=3010), les patients operes d’une tumeur pTis ou pT1 ont ete extraits et analyses de facon comparative entre ADCI et NADCI sur les parametres demographiques, operatoires, histologiques, postoperatoires et pronostiques. L’objectif primaire etait de comparer la survie a 3 ans entre ADCI et NADCI. Resultats Parmi les 421 patients porteurs d’une tumeur superficielle pTis ou pT1, 104 cas (24,7 %) appartenaient au groupe ADCI et 317 cas (75,3 %) au groupe ADNCI. Hormis comme attendu des patients plus jeunes dans le groupe ADCI (59,6 vs. 68,8 ans, p Conclusion Dans les formes superficielles de cancer gastrique, le type ADCI n’est pas un facteur de mauvais pronostic.

Background Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. Methods/design PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. Discussion This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. Trial registration NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014)

The aim of this retrospective study was to evaluate the survival impact of perioperative chemotherapy (PCT) in patients with gastric signet ring cell (SRC) adenocarcinoma.PCT is a standard treatment for advanced resectable gastric adenocarcinoma (GA). SRC has a worse prognosis compared to non-SRC and the chemosensitivity of SRC is uncertain.Among 3010 patients registered in 19 French centers between January 1997 and January 2010, 1050 (34.9%) were diagnosed with SRC. Of those treated with curative intent (n = 924), 171 (18.5%) received PCT with surgery (PCT group), whereas 753 (81.5%) were treated with primary surgery (S group). PCT was based mainly on a fluorouracil-platinum doublet or triplet regimen.The groups were comparable regarding age, gender, American Society of Anesthesiologists (ASA) score, malnutrition, tumor location and cTNM stage. 60 patients did not undergo resection because of tumor progression (10) or metastases (50) found at operation. The R0 resection rates were 65.9% and 62.3% in the S and PCT groups, respectively (P = 0.308). Fewer patients received adjuvant chemotherapy in the S group than in the PCT group (35.2% vs. 66.5%, P0.001). At a median follow-up of 31.5 months, the median survival was shorter in the PCT group (12.8 vs. 14.0 months, P = 0.043). On multivariate analysis, PCT was found to be an independent predictor of poor survival (HR = 1.4, 95% CI 1.1-1.9, P = 0.042).PCT provides no survival benefit in patients with gastric SRC. Clinical Trial.gov record: ADCI001, Clinical Trial.gov identifier NCT01249859.

To test the hypothesis that signet ring cell (SRC) histology has a negative prognostic value in patients with gastric adenocarcinoma (ADC).In western countries, gastric ADC with SRC often occurs after the disease has advanced. Consequently, the prognosis of SRC is generally regarded as poor, although survival studies comparing SRC and non-SRC have yielded inconsistent results.: An intent to treat analysis was performed among 215 patients with gastric ADC scheduled for surgical resection from 1996 to 2007. Of these, 180 patients underwent the resection and 35 were not resected due to diffuse metastatic illness. From 59 resected patients with SRC (SRC group), control non-SRC resected patients matched by age, gender, American Society of Anaesthesiologists (ASA) classification, tumoral location, and pTNM stage were randomly selected by computer (non-SRC group: n = 100) during the same study period.The overall median survival was 21 months, which was significantly higher in resected compared to non-resected patients (31 vs. 5 months, P0.001). In non-resected patients, SRC histological subtype was associated with higher rates of diffuse peritoneal carcinomatosis (90.1% vs. 62.5%, P = 0.053) and neoplastic ascitis (63.6% vs. 34.7%, P = 0.059) and poorer median survival (5 vs. 7 months, P = 0.062). For resected patients, the 2 groups (SRC and non-SRC) were comparable regarding matching variables, demographic variables, and postoperative course. The median survival was significantly lower for SRC patients (21 vs. 44 months, P = 0.004). SRC resected patients exhibited higher rates of localized peritoneal carcinomatosis (P = 0.013) and lymph node involvement (P0.001) at diagnosis, lower R0 resection rate (P = 0.019) and earlier tumor relapse (P = 0.009), which was generally in a peritoneal carcinomatosis form (P = 0.011). By multivariate analysis, we concluded that SRC histology was independently associated with a dismal prognosis after adjustment on confounding variables (hazard ratio = 1.5, 95% confidence interval 1.1-2.0, P = 0.004). The prognostic role of SRC was maintained after exclusion of patients with advanced stage at initial diagnosis such as localized peritoneal carcinomatosis or lymph node invasion.This study is currently the best evidence showing that SRC is a major and independent predictor of poor prognosis due to specific characteristics such as more infiltrating tumors showing affinity for lymphatic tissue accompanied by a higher rate of peritoneal carcinomatosis. Our results suggest the need for a specific therapeutic strategy for such tumors.

This study was designed to investigate the impact of laparoscopic gastric mobilization (LGM) on 30-day postoperative mortality (POM) after surgery for esophageal cancer (EC).Meta-analyses of nonrandomized studies have failed to demonstrate any significant benefit of hybrid minimally invasive esophagectomy on POM, potentially due to small population samples. Moreover, none of the published randomized trials have been designed to answer this question.All consecutive patients who underwent EC resection between 2010 and 2012 in France were included in this nationwide study (n = 3009). Data were extracted from the French National Health Service Database with internal and external quality controls. Patients treated with LGM (LGM group, n = 663) were compared with those treated with open approach (open group, n = 2346). Propensity score matching and multivariable analyses were used to compensate for the differences in baseline characteristics.The 30-day POM rate was 5.2%, significantly lower after LGM, compared with open surgery (3.3% vs 5.7%, P = 0.005), as well as in-hospital (5.6% vs 8.1%, P = 0.028), and 90-day POM (6.9% vs 10.0%, P = 0.016). After propensity score matching, 30-day POM rates were 3.3% versus 5.9%, respectively (P = 0.029). By multivariable analysis, age ≥60 years, malnutrition and cardiovascular comorbidity were independently associated with higher POM, whereas LGM was associated with a decrease in POM (OR 0.60, 95% CI 0.37-0.98, P = 0.041).This all-inclusive nationwide study strongly suggests that POM is significantly reduced after LGM for EC. This is high valuable evidence that helps decision making regarding the optimal approach for EC surgery.

International audience; BACKGROUND:Perioperative oncologic treatments provide a survival benefit for junctional and gastric adenocarcinoma (JGA) and esophageal cancer (EC). Whether neoadjuvant therapy toxicity (NTT) correlates with increased perioperative risk remains unclear. We aimed to evaluate the impact of grade III/IV NTT on postoperative and oncologic outcomes in resected upper gastrointestinal malignancies.METHODS:A multicenter retrospective analysis was performed on consecutive patients who benefited from neoadjuvant chemo(radio)therapy followed by surgery between 1997 and 2010 for JGA (first cohort, n = 653) and for EC (second cohort, n = 640). Data between patients who experienced NTT were compared to those who did not.RESULTS:NTT was associated with higher postoperative mortality after resection of JGA (P = 0.001) and after esophagectomy (P < 0.001), more non-R0 resections (JGA P = 0.019, EC P = 0.024), a decreased administration of adjuvant treatment among the JGA cohort (P = 0.012), and higher surgical morbidity (JGA P = 0.005, EC P = 0.020). Median survival was reduced in patients who experienced NTT in both cohorts (JGA P = 0.018, EC P = 0.037). After adjustment on confounding variables, NTT was independently associated with postoperative mortality in both cohorts (P ≤ 0.007).CONCLUSIONS:NTT is a predictor of postoperative mortality, correlates with higher postoperative morbidity, and negatively affects oncologic outcomes for upper gastrointestinal carcinomas.

International audience; Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers in the world with one of the worst outcome. The oncogenic mucin MUC4 has been identified as an actor of pancreatic carcinogenesis as it is involved in many processes regulating pancreatic cancer cell biology. MUC4 is not expressed in healthy pancreas whereas it is expressed very early in pancreatic carcinogenesis. Targeting MUC4 in these early steps may thus appear as a promising strategy to slowdown pancreatic tumorigenesis. miRNA negative regulation of MUC4 could be one mechanism to efficiently downregulate MUC4 gene expression in early pancreatic neoplastic lesions. Using in silico studies, we found two putative binding sites for miR-219-1-3p in the 3 0-UTR of MUC4 and showed that miR-219-1-3p expression is downregulated both in PDAC-derived cell lines and human PDAC tissues compared with their normal counterparts. We then showed that miR-219-1-3p negatively regulates MUC4 mucin expression via its direct binding to MUC4 3 0-UTR. MiR-219-1-3p overexpression (transient and stable) in pancreatic cancer cell lines induced a decrease of cell proliferation associated with a decrease of cyclin D1 and a decrease of Akt and Erk pathway activation. MiR-219-1-3p overexpression also decreased cell migration. Furthermore, miR-219-1-3p expression was found to be conversely correlated with Muc4 expression in early pancreatic intraepithelial neoplasia lesions of Pdx1-Cre;LSL-Kras G12D mice. Most interestingly, in vivo studies showed that miR-219-1-3p injection in xenografted pancreatic tumors in mice decreased both tumor growth and MUC4 mucin expression. Altogether, these results identify miR-219-1-3p as a new negative regulator of MUC4 oncomucin that possesses tumor-suppressor activity in PDAC.

Dans son ultime seminaire au College de France consacre aux photographies du « monde proustien », Barthes fait le vœu d’engager une parole de l’a-cote, presque buissonniere, qui ne ferait que legender les images aimees sans les grever du poids de la theorie. Cet article retraverse les legendes photographiques de l’œuvre de Barthes, depuis le Michelet jusqu’a La Chambre claire. Il tâche de rendre compte d’une forme gratuite de l’ecriture du critique, jamais consideree comme telle en raison meme de sa position decrochee. Or, c’est precisement en raison de cette tenue peripherique, inscrite dans la marge d’une pratique d’amateur et comme li beree, qu’on peut y lire la trace certaine d’un investissement poetique.

The signet ring cell (SRC) histological subtype is a factor of poor prognosis in advanced gastric adenocarcinomas, but its prognostic value in early gastric cancer is unclear. The aim of this study was to evaluate the prognostic impact of SRC in superficial gastric adenocarcinomas, based on a comparison of patients with SRC and non SRC histologies.From a large national cohort of 3,010 patients operated on for gastric adenocarcinoma between January 1997 and January 2010, we selected patients with pTis or pT1 tumors and compared those with SRC and non SRC histology on the basis of demographic, surgical and histologic factors and outcomes. The primary endpoint was the 3-year survival rate.Among 421 patients with a pTis or pT1 tumor, 104 (24.7%) had the SRC subtype and 317 (75.3%) a non SRC subtype. Median age was significantly lower in the SRC group than in the non SRC group (59.6 vs 68.8 years, p0.001). Other demographic variables were similar in the two groups. Extensive surgical resection was more frequent in the non SRC group (31.9% vs 12.5%, p0.001), but R0 resection rates were similar (97.5% vs 98.1%, p=0.900). The submucosa was more frequently involved in the SRC group (94.2% vs 84.9%, p=0.043), while lymph node involvement and the number of invaded nodes were similar in the two groups. Recurrences (5.8% vs 8.8%, p=0.223) and sites of recurrence (especially peritoneal carcinomatosis, 1.9% vs 1.6% ; p=0.838) were similar in the two groups. The 3-year survival rate was similar in the SRC and non SRC groups (94.1% vs 89.9%, p=0. 403), although the median survival time had not been reachedSRC is not a prognostic factor in superficial gastric adenocarcinoma.

To date, for esophageal cancer (EC), the optimal timing of surgical procedures after neoadjuvant chemoradiation (nCRT) is not well defined. Data in rectal cancer suggest that a prolonged interval between treatment and operation may improve tumoral pathologic response, R0 resection rate, and survival. The aims of this study were to evaluate whether delaying operation after nCRT in EC increases pathologic response and has an impact on oncologic outcome or postoperative course.A total of 257 consecutive EC patients (n=161 squamous cell carcinomas and n=96 adenocarcinomas) undergoing nCRT followed by operation between 1997 and 2011 were retrospectively analyzed by the use of prospectively collected data. The patients were divided into two groups according to the median delay between nCRT and operation (7 weeks, n=122; ≥7 weeks, n=135). The impact of surgical delay on outcomes was studied through univariable and multivariable analyses.The groups were comparable regarding patient and tumor characteristics (p≥0.074). The ypT0 and R0 resection rates were similar between the two groups, as were postoperative course, median survivals, and incidence and patterns of recurrence (p≥0.332). Multivariable analysis failed to identify any impact of the surgical delay on the endpoints. Subgroup analysis according to the histologic type found similar results.After nCRT for EC, delaying operation does not affect the ypT0 rate, postoperative course, or oncologic outcome and cannot therefore be justified by these aims.

Cet article est un compte-rendu du livre : Aurélie Adler, Éclats des vies muettes. Figures du minuscule et du marginal dans les récits de vie d’Annie Ernaux, Pierre Michon, Pierre Bergounioux et François Bon, Paris : Presses de la Sorbonne nouvelle, 2012, 330 p., EAN 9782878545722.

Although the signet ring cell histologic subtype (SRC) is an independent predictor of poor prognosis in advanced gastric adenocarcinomas (GA), its prognostic value in early GA remains highly controversial. The aim of the study was to evaluate the prognostic impact of SRC in mucosal and submucosal GAs.Based on a multicenter cohort of 3,010 patients operated on for GA between January 1997 and January 2010, patients with pTis or pT1 tumors were extracted and analyzed comparatively between the SRC and non-SRC groups. The primary objective was to compare the 5-year survival rate between groups.Among 421 patients with a pTis or pT1 tumor, 104 (25%) were SRC and 317 (75%) were non-SRC. Demographic variables were comparable between groups, except median age, which was less in the SRC group (59.6 vs 68.8 years; P.001). Submucosal involvement was more frequent in the SRC group (94% vs 85%; P = .043), whereas lymph node involvement and number of invaded nodes were comparable between the 2 groups. When comparing SRC and non-SRC, recurrence rates (6% vs 9%; P = .223) and sites of recurrence were similar. The 5-year overall survival benefit in SRC patients (85% vs 76%, respectively; P = .035), was not evident when considering exclusively disease-specific survival or in multivariable analysis.Contrary to more advanced GA, SRC morphologic subtype is not a negative prognostic factor in early GA. Better survival identified in some reports may be related to the younger age in SRC patients.

International audience; BACKGROUND: A dramatic increase in the incidence of the diffuse form of gastric adenocarcinomas and particularly signet ring cell carcinomas has been observed in Western countries. Evidence is accruing that signet ring cell carcinomas may have inherent chemo resistance leaving many clinicians unsure of the benefits of delaying surgery to pursue a neoadjuvant approach. METHODS/DESIGN: PRODIGE-19-FFCD1103-ADCI002 is a prospective multicentre controlled randomised phase II/III trial comparing current standard of care of perioperative chemotherapy (2x3 cycles of Epirubicin, cisplatin, 5-fluorouracil) with a strategy of primary surgery followed by adjuvant chemotherapy (6 cycles of Epirubicin, cisplatin, 5-fluorouracil) in patients with a stage IB-III gastric signet ring cell tumour. The principal objective of the phase II study (84 patients) is to determine if the experimental arm (primary surgery followed by adjuvant chemotherapy) has sufficient interest in terms of percentage of living patients at 24 months to be evaluated in a phase III trial. If 7 or less patients in the experimental arm are alive at 24 months, phase III will not be initiated. The primary objective of phase III (230 additional patients) is to demonstrate superiority of the experimental arm in terms of overall survival. Secondary endpoints include overall survival at 36 months, disease free survival at 24 and 36 months, R0 resection rates, treatment tolerance, postoperative mortality and morbidity evaluated by Clavien-Dindo severity index, the prognostic impact of positive peritoneal cytology and the assessment of quality of life. An ancillary study will assess the emotional and cognitive impact of surgery and perioperative chemotherapy for both the patient and their partner. DISCUSSION: As inherent chemo resistance of signet ring cell tumours and delay in definitive surgery may favour tumour progression we hypothesise that a policy of primary surgery followed by adjuvant chemotherapy will improve overall survival compared to a standard perioperative chemotherapeutic strategy. This randomised phase II/III trial is the first dedicated to this histological subtype. Whilst the development of new biomarkers and targeted therapies are awaited, the results of this trial should further help in devising individualised protocols of patient care in a tumour group whose diversity increasingly demands assessment of alternative strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01717924.

Cet article est un compte-rendu du livre : Roland Barthes, Sarrasine de Balzac. Séminaires à l’École pratique des hautes études (1967-1968 et 1968-1969), Paris : Éditions du Seuil, coll. « Traces écrites », 2011, 608 p., EAN 9782020618526.

Whereas palliative chemotherapy offers a median survival of approximately 10 months in advanced gastric and junctional adenocarcinoma (AGJA), the survival impact of primary tumor resection is controversial. Our purpose was to identify which AGJA patients benefit from palliative resection.In 3,202 AGJA patients scheduled for surgery in 21 French centers between 1997 and 2010, prognostic factors were identified in palliative group and the impact of each combination of these factors on survival was studied.Surgery was defined as palliative due to solid organ metastasis (5.6 %), localized (4.6 %) or diffuse (2.3 %) peritoneal carcinomatosis (PC), or incomplete tumoral resection (12.8 %). Median survival of AGJA patients resected with a palliative intent (n = 677) was longer than in nonresected patients (n = 532; 11.9 vs. 8.5 months, P 0.001). Multivariable analyses identified ASA score III-IV (P 0.001) as a predictor of postoperative mortality and solid organ metastasis (P = 0.009), localized PC (P = 0.004), diffuse PC (P = 0.046), and signet ring cell histology (SRC; P = 0.02) as predictors of survival. Only ASA I-II patients with incomplete resection without metastasis or PC, one site solid organ metastasis without PC, or localized PC without SRC had a survival benefit after palliative surgery with median survivals from 12.0 to 18.3 months. Nonresected ASA I-II patients with same risk factors had median survivals from 3.5 to 8.8 months (P 0.05 for each).In AGJA, patient and tumor-related factors should be used to select candidates for palliative surgery in association with chemotherapy.

Cet article est un compte-rendu du livre : Pascal Quignard & Irène Fenoglio, Sur le désir de se jeter à l’eau, Paris : Presses de la Sorbonne nouvelle, coll. « Archives », 2011, 305 p., EAN 9782878545432.

Objectif La chimiotherapie peri-operatoire est le standard de traitement des adenocarcinomes gastriques et de la jonction (AEJ). Cependant pres de 50 % des patients des essais randomises ne beneficient pas de la chimiotherapie adjuvante (CTa). Le but de ce travail etait d’evaluer l’interet de la CTa sur la survie et d’identifierles facteurs predictifs de sa non realisation. Methodes A partir d’une base multicentrique de 3 202 AEJ, 438 patients traites par chimiotherapie neoadjuvante et chirurgie etaient eligibles a une CTa. Resultats La CTa n’a pas ete realisee chez 148 patients (33,8 %). La survie etait meilleure chez ceux ayant recu une CTa : 26,8 vs 15,2 mois, p 60 ans (OR 2,4 p 30 j (OR 2,3 p = 0,011). Conclusion Pour les AEJ engages dans une strategie peri-operatoire la CTa offre un benefice de survie. Les facteurs predictifs de sa non realisation suggerent au-dela d’une optimisation nutritionnelle, d’intensifier la chimiotherapie neoadjuvante chez ces patients a risque de non realisation de la CT.

But du travail Les strategies de radiochimiotherapie (RCT) exclusive et de RCT neo-adjuvante sont deux options de traitement a visee curative du cancer de l’œsophage. Le but du travail etait de comparer les survies des patients en reponse complete apres RCT exclusive (groupe RCTE) versus apres RCT suivie de chirurgie (groupe RCTC). Patients et Methodes De 1995 a 2007, parmi 1176 patients traites pour cancer de l’œsophage, une etude cas temoins en intention de traiter a ete realisee a partir de 55 patients du groupe RCTE appareilles a 111 patients temoins du groupe RCTC selon les criteres d’âge, de sexe, de localisation et de stade tumoral, de score ASA, de type histologique et de denutrition. La reponse a la RCT etait evaluee par fibroscopie+ biopsies et tomodensitometrie dans le groupe RCTE et l’anatomopathologie sur la tumeur primitive dans le groupe RCTC. Resultats Les deux groupes etaient comparables avec, dans les groupes RCTE et RCTC respectivement, un âge moyen de 59 vs 57 ans, un taux de carcinomes epidermoides de 87 % vs 91 %, un score ASA 2 ou 3 de 65 % vs 76 %, une localisation tumorale au tiers moyen ou inferieur de l’œsophage dans 71 % vs 77 % des cas et une tumeur avancee dans 64 % vs 60 % des cas. Les delais moyens d’apparition de la recidive etaient respectivement de 10 vs 18 mois (p = 0,012). Les medianes et taux de survie a 5 ans etaient respectivement de 25 vs 61 mois et 19 % vs 50 % (p = 0,001). Conclusion La survie des patients en reponse complete est meilleure apres RCT suivie de chirurgie qu’apres RCT exclusive. Il convient donc d’operer si possible ces patients, pour un meilleur controle locoregional de la maladie mais surtout parce que l’evaluation de la reponse complete morphologique apparait ineffective.

Importance Postoperative mortality after junctional and gastric adenocarcinoma resection remains a significant issue. Objective To identify factors predictive of mortality within 30 days of junctional and gastric adenocarcinoma resection in a large national multicenter cohort. Design A retrospective study collecting data from a multicenter database of patients who underwent resection for junctional and gastric adenocarcinoma from January 1, 1997, through January 31, 2010. A stepwise logistic regression model was built to identify, by multivariate analysis, variables independently predictive of 30-day postoperative mortality (POM). Setting Nineteen university teaching hospitals in France. Participants Two thousand six hundred seventy patients with available data. Main Outcome Measures The primary end point was POM. Secondary end points included (1) late mortality (30-90 days after resection) and (2) postoperative morbidity. Results One thousand eight hundred ninety-six patients (71.01%) had gastric adenocarcinoma and 774 (28.99%) had junctional tumors. Neoadjuvant treatment was given to 655 patients (24.53%), and 114 patients (4.27%) died within 30 days of surgery. Postoperative mortality was higher in patients who experienced grades III and IV toxic effects during neoadjuvant treatment compared with those who did not (8.7% vs 2.9%, respectively; P = .007). Multivariate analysis revealed metastatic disease at diagnosis (odds ratio, 9.13 [95% CI, 3.29-25.35]; P P = .02) as being independently predictive of POM. Centers performing at least 10 resections per year were found to be protective against POM (odds ratio, 0.29 [95% CI, 0.12-0.72]; P = .008). Conclusions and Relevance This large national cohort study confirms that advanced disease heightens the risk of POM; centralization of junctional and gastric adenocarcinoma resection is warranted. The novel finding that grades III to IV toxic effects during neoadjuvant therapy increase POM has significant implications for decision making in this subgroup of patients. Trial Registration clinicaltrials.gov Identifier:NCT01249859

4036 Background: Perioperative chemotherapy is a standard treatment for gastric adenocarcinoma (GA). Signet ring cell GA (SRC) has been shown to be of poorer prognosis when compared to non-SRC. Alt...

4089 Background: Exclusive chemoradiotherapy and chemoradiotherapy (CRT) followed by surgery are two optional strategies for curative treatment of oesophageal cancer. The aim of this study was to c...

Background To identify predictors of long-term outcome for patients with clinical complete response (cCR) after definite chemoradiotherapy (CRT) or radiation therapy (RT) for oesophageal cancer (EC). Methods In this retrospective study, we reviewed the files of all patients from our institution that underwent definitive RCT or RT for EC, from January 1998 to December 2003. Among 402 consecutive patients with EC, 110 cCR responses were observed, i.e. without evidence of tumour on morphological examination of the biopsy specimens, 8 to 10 weeks after radiation. Baseline patient and tumour characteristics were as follows: male = 98/110, median age = 60, squamous histology = 103/110, tumour site (upper/middle/lower third) = 41/50/19, weight loss none/

We report two clinical cases of primary granulocytic sarcoma of the pancreas that were diagnosed on the surgical specimen. Atypical clinical and morphological presentations may have lead to pretherapeutic biopsies of the pancreatic mass in order to indicate primary chemotherapy. Literature review of this rare clinical presentation may help physicians to anticipate diagnostic and therapeutic strategies.