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Immunotherapy with immune checkpoint inhibitors has significantly improved the survival of patients with MSI/dMMR mCRC. These tumors are associated with a specific metastatic spread, i.e. frequent peritoneal carcinomatosis (PC) that may be treated surgically when there is no other metastatic location. We aimed at evaluating the prognosis of patients treated with immune checkpoint inhibitors for MSI/dMMR mCRC with isolated PC.All consecutive patients with isolated PC from MSI/dMMR mCRC, initially considered as unresectable by multidisciplinary team meeting, treated with immune checkpoint inhibitors were included in this French multicenter cohort study.Among 45 patients included, we observed 11 complete responses and 10 partial responses for an overall response rate iRECIST of 46%. After a median follow-up of 24.4 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. Seven of the eight patients who underwent cytoreductive surgery after treatment with anti-PD1 ± anti-CTLA-4 were in complete pathologic response.These results demonstrate long-term benefit of immune checkpoint inhibitors for patients with isolated PC from MSI/dMMR mCRC. Such treatment appears as the best therapeutic option for patients with isolated PC from MSI/dMMR mCRC. With a majority of pathological complete responses for patients who underwent surgery for residual lesions, the value of such therapeutic strategy remains unknown.

To assess the impact of surgical approach on morbidity, mortality, and the oncological outcomes of synchronous (SC) and metachronous (MC) colorectal cancer (CRC).All patients undergoing resection for double location CRC (SC or MC) between 2006 and 2020 were included. The exclusion criteria were polyposis or SC located on the same side.Sixty-seven patients (age, 64.8 years; male, 78%) with SC (n = 41; 61%) or MC (n = 26; 39%) were included. SC was treated with segmental colectomy (right and left colectomy/proctectomy; n = 19) or extensive colectomy (subtotal/total colectomy or restorative proctocolectomy with pouch; n = 22). Segmental colectomy was associated with a higher incidence of anastomotic leakage (47.4 vs. 13.6%; p = 0.04) and a higher rate of medical morbidity (47.4 vs. 16.6%; p = 0.04). The mean number of lymph nodes harvested was similar. For MC, the second cancer was treated by iterative colectomy (n = 12) or extensive colectomy (n = 14) and there was no significant difference in postoperative outcomes between the two surgical approaches. The median follow-up period was 42.4 ± 29.1 months. The 5-year overall and disease-free survival of the SC and MC groups did not differ to a statistically significant extent.Extensive colectomy should be preferred for SC to reduce morbidity and improve the prognosis. In contrast, iterative colectomy can be performed safely for patients with MC.

International audience; PurposeThe present study assessed the factors associated with the maintenance of a functional anastomosis in a large consecutive series of patients with anastomotic leakage (AL).MethodsAll consecutive patients presenting with AL after colorectal or coloanal anastomosis (2012–2019) were analyzed. The primary end point was a functional anastomosis without a stoma at 1 year.ResultsA total of 156 patients were included. AL was initially treated by antibiotics (38%), drainage (43%) or urgent surgery (19%). Initial treatment of AL was not adequate in 24.3%, and reintervention in the form of drainage or surgery was required. A total of 60.9% of patients had a functional anastomosis without a stoma 1 year after surgery. Factors associated with the risk of anastomotic failure at 1 year were diabetes (odds ratio [OR] = 4.24 [95% confidence interval {CI} 1.39–14.24] p = 0.014), neoadjuvant chemoradiotherapy (OR = 3.03 [95% CI 1.14–8.63] p = 0.03) and Grade B (OR = 6.49 [95% CI 2.23–21.74] p = 0.001) or C leak (OR = 35.35 [95% CI 9.36–168.21] p

A stoma exposes patients to several complications which could impair their quality of life (QoL). In the last decade, the market for stoma therapy in France has evolved, with a significant increase in the activities of home health providers, meeting a need for patient follow-up and companionship. International studies have demonstrated the impact of the stoma therapist (ST) follow-up on the improvement of an ostomy patient's QoL. However, the impact of home stoma nurse management has not been analysed. In this context we would like to assess the added value on health-related QoL from the enhanced follow-up of ostomy patients by STs.This is a randomized, controlled, open, national and multicentre trial (12 centres) which includes patients with an ostomy who benefit from either standard follow-up or from an enhanced and personalized follow-up with, in particular, regular consultations with an ST after discharge. The primary end-point is the 3-month QoL score obtained from the Stoma-QoL questionnaire. The secondary end-points are satisfaction of the care, comparison of QoL scores (Stoma-QoL and EuroQuol EQ-5D) and the economic gains by calculating the consumption of resources between the two arms. There will be a modified intention-to-treat analysis with 6-month follow-up in both study arms.The StomaCare trial will be the first randomized controlled study in France to evaluate the impact on QoL of an enhanced follow-up at home of ostomy patients by an ST.

Data on preimplantation genetic testing (PGT-M) in patients with genetic susceptibility to cancer are scarce in the literature, while there is, in our experience, a growing familiarity with assisted reproduction techniques (ART) among pathogenic variant heterozygotes. We performed a retrospective multicenter study of PGT-M outcomes among French patients with genetic susceptibility to cancer. Our objectives were to collect data on this complex issue, and to help cancer geneticists counsel their patients of reproductive age. We also wanted to increase awareness regarding PGT-M among cancer genetics professionals. Patients from three university hospital cancer genetics clinics who had requested PGT-M between 2000 and 2019 were included retrospectively. Data were extracted from medical records. Patients were then contacted directly to collect missing and up-to-date information. Out of 41 eligible patients, 28 agreed explicitly to participate when contacted and were therefore included. They carried PV in VHL (n = 9), APC (n = 8), CDH1 (n = 5), STK11 (n = 2), AXIN2, BRCA1, MEN1, and FH (n = 1). Seven patients were denied PGT-M based on multidisciplinary team meetings or subsequently by the ART hospital teams, two changed their minds, and two were yet to start the process. PGT-M was successful in seven patients (25%), with a mean age at PGT-M request of 27. Most had von Hippel-Lindau. PGT-M failed in the remaining ten, with a mean age at PGT-M request of 32. The main reason for failure was non-implantation of the embryo. Of these, four patients were pursuing PGT-M at the time of last contact. PGT-M outcomes in patients with cancer susceptibility syndromes were satisfactory. These patients should be informed about PGT-M more systematically, which would imply greater awareness among cancer genetics professionals regarding ART. Our series was not representative of cancer susceptibility syndromes in general; the predominance of cases with syndromes characterized by early-onset, highly penetrant disease is explained by the restrictive French guidelines.

Background Since 2006, surgery combined with perioperative chemotherapy is the standard of care for resectable gastric adenocarcinoma in Europe. Specific effects of neoadjuvant chemotherapy remain unknown. The aim was to evaluate the rate of tumor downstaging and its impact on survival in patients undergoing curative resection after neoadjuvant chemotherapy (NeoCT) for gastric adenocarcinoma. Material and Methods All patients treated in a curative intent for gastric or esophagogastric junction adenocarcinomas between 1996 and 2016 in our high-volume center were retrospectively included. Tumor downstaging after NeoCT was defined as ypTN inferior to cTN. The accuracy of clinical staging was evaluated in patients treated by upfront surgery before 2006. Results During the study period, 491 patients were operated for gastric adenocarcinoma, and 449 patients were finally analyzed. Among the 163 (36.3%) patients who received NeoCT, 61 (37.4%) had tumor downstaging. Overall survival and disease-free survival were longer in patients with tumor downstaging compared to patients without it (5-year survival: 84.8% vs 49.7%; P = .002 and 61.7% vs 43.4%; P = .054). In multivariate analysis tumor downstaging was an independent prognosis factor for better overall survival (HR = 5.258; P = .002) and disease-free survival (HR = 2.286; P = .028). Moreover, 45.5% of patients staged cT1-T2N0, in whom upfront surgery was performed, were understaged and ultimately had a more advanced tumor on pathological analysis. Conclusion Response to neoadjuvant chemotherapy constitutes a major prognostic factor for overall and disease-free survival. In the absence of predictive factors for tumor downstaging, the indication for perioperative chemotherapy should remain broad, in particular because of the low accuracy of pretherapeutic staging and therefore the high risk of understaging tumors.

International audience

C-reactive protein (CRP) is a useful predictive test to early detect abdominal complication after colorectal surgery. Inflammatory bowel disease (IBD) is responsible for chronic inflammation and abnormal basal CRP that could influence the interest of its management after abdominal surgery. The aim of this study is to evaluate CRP as an indicator of postoperative complication in a specific IBD population.Retrospective study of patients undergoing ileocolic resection or ileal pouch-anal anastomosis for IBD between 2012 and 2019.Ileocolic resection represents 242 patients and ileal pouch-anal anastomosis 105 patients. CRP was significantly higher at an early (105.2 ± 56.0 vs 128.1 ± 69.8; p = 0.008) and late stage (112.9 ± 72.8 vs 185.3 ± 111.5; p 0.0001) for patients having an intra-abdominal complication. A BMI 25 kg/mCRP is a useful predictive marker to detect abdominal complication after surgery in IBD population. Measurement of CRP can help to reduce hospitalization stay and orientate towards complementary examinations.

International audience; BackgroundLaparoscopy for gastric cancer has not been as popular compared with other digestive surgeries, with conflicting reports on outcomes. The aim of this study focuses on the surgical techniques comparing open and laparoscopy by assessing the morbi-mortality and long-term complications after gastrectomy.MethodsA retrospective study (2013–2018) was performed on a prospective national cohort (PMSI). All patients undergoing resection for gastric cancer with a partial gastrectomy (PG) or total gastrectomy (TG) were included. Overall morbidity at 90 post-operative days and long-term results were the main outcomes. The groups (open and laparoscopy) were compared using a propensity score and volume activity matching after stratification on resection type (TG or PG).ResultsA total of 10,343 patients were included. The overall 90-day mortality and morbidity were 7% and 45%, with reintervention required in 9.1%. High centre volume was associated with improved outcomes. There was no difference in population characteristics between groups after matching. An overall benefit for a laparoscopic approach after PG was found for morbidity (Open = 39.4% vs. Laparoscopy = 32.6%, p = 0.01), length of stay (Open = 14[10–21] vs. Laparoscopy = 11[8–17] days, p

To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM).Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative.A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression.A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25).Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

International audience; BackgroundBladder invasion by colon cancer is rare; however, its management is still controversial. Our objective was to report outcomes and identify risk factors for local recurrence in colon cancer with clinically suspected bladder invasion.MethodsWe conducted a retrospective study in 23 centers in France. All patients who underwent colon surgery with bladder resection (2010–2017) were included. Metastatic and recurrent colon cancers were excluded.ResultsOne hundred and seventeen patients (men = 73) were included. Partial cystectomy occurred in 108 patients (92.3%), with a total cystectomy occurring in 9 patients (7.7%). Neoadjuvant treatment was given to 31 patients (26.5%). Major morbidity was 20.5%. R0 resection rates were 87.2%. Histologically confirmed bladder invasion was present in 47%. Thirty-four patients were pN+, while 60 patients (51.3%) received adjuvant chemotherapy. Mean follow-up was 33.8 months. Three-year overall survival and disease-free survival were 82.9% and 59.5%. Rates of local recurrence and distant recurrence were 14.5% and 18.8%, respectively; the local recurrences (11/17; 65%) were in the bladder, while 4 of these patients had a bladder recurrence despite not having histologically confirmed bladder invasion at the index surgery. The rate of bladder recurrence after histologic bladder invasion was 13% (7/55), while the rate of bladder recurrence without primary bladder invasion was 7% (4/62) (P = .343). Neoadjuvant therapy, type of cystectomy, and adjuvant therapy did not influence local recurrence (P > .445 each). R1 bladder resections, when compared with a R0 bladder resections, were associated with an increased rate of local recurrence (63% vs 10%; P < .0001).ConclusionClinically suspected bladder invasion increases local recurrence even in the absence of histologically confirmed bladder invasion. Only complete resections with R0 margins decrease local recurrence. Careful, detailed postoperative surveillance is required, even without pathologic bladder invasion.

Immune checkpoint inhibition (CPI) for metastatic colorectal cancer (mCRC) with deficient mismatch repair (dMMR) demonstrates high clinical activity that appears durable, but the impact of CPI on pathological tumor response is unknown. In this retrospective analysis, our objective was to assess pathological response and clinical outcomes in dMMR mCRC patients treated with CPI prior to surgical resection of primary and/or metastatic tumor. Among 121 advanced dMMR mCRC patients treated with CPI at 2 institutions between November 2016 and December 2018, 14 underwent surgery. Pathologic complete response was noted in the resected specimens of 13 patients despite the presence of residual tumor on preoperative imaging in 12 of those patients. With median follow-up of 9 months, no patients have had disease relapse or progression. For this small retrospective study, the data suggest that residual radiographic tumor may not require systematic resection following response to anti-PD1–based therapy. However, larger prospective studies are warranted.

The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire was developed in response to the need for a new, fast, and comprehensive tool for evaluating quality of life in patients who have colorectal cancer. Available surveys such as the SF-12, SF-36, Functional Assessment of Cancer Therapy-Colorectal, and European Organization for Research and Treatment of Cancer are either too general to be informative or too lengthy to complete.The aim was to validate the Cleveland Clinic Foundation Colorectal Quality of Life Questionnaire.Data were obtained as part of a prospective randomized controlled trial.This was a worldwide multicenter study with 2 domestic and 5 international locations.This study randomly assigned 190 patients between the ages of 18 and 80 undergoing surgery for low rectal cancer. Of those randomly assigned, 142 with partially complete surveys were analyzed for selection bias and acceptability, and 95 with complete surveys were analyzed for survey validity.Patients received either a J-pouch, side-to-end anastomosis, or straight anastomosis.The study evaluated survey validity measures such as standardized Cronbach α for internal consistency and Spearman correlation coefficients for construct validity, convergent validity, and responsiveness. Univariate analyses were used to assess discriminative validity.Sufficient acceptability, construct, and convergent validity and responsiveness were achieved. All scores showed great internal consistency (Cronbach α0.8). Superior discriminative ability was demonstrated by significant differences (p0.05) in 2 of 7 scores between neoadjuvant treatment groups, and in 6 of 7 scores between complication groups, none of which were detected by the SF-12 or Functional Assessment of Cancer Therapy-Colorectal surveys.Limitations included a small sample size, cultural differences, and failure to assess test-retest ability of the questionnaire.The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire is an efficient and reliable quality-of-life measure that better incorporates factors specific to colorectal cancer surgery. See Video Abstract at http://links.lww.com/DCR/B155. REDUCIENDO LA CARGA AL PACIENTE Y MEJORANDO LA CALIDAD DE DATOS CON EL NUEVO CUESTIONARIO DE CALIDAD DE VIDA EN CÁNCER COLORRECTAL DE CLEVELAND CLINIC (CCF-CAQL): El cuestionario de calidad de vida en cáncer colorrectal de Cleveland Clinic se desarrolló en respuesta a la necesidad de una herramienta nueva, rápida e integral para evaluar la calidad de vida en pacientes con cáncer colorrectal. Los cuestionarios disponibles como SF-12, SF-36, FACT-C y EORTC son demasiado generales para ser informativas o demasiado largas para completar.El objetivo fue validar el cuestionario de calidad de vida colorrectal de la Cleveland Clinic Foundation.Los datos se obtuvieron como parte de un ensayo prospectivo aleatorizado y controlado.Este fue un estudio multicéntrico mundial con dos sedes nacionales y cinco internacionales.Este estudio aleatorizó a 190 pacientes entre las edades de 18 y 80 sometidos a cirugía por cáncer rectal bajo. De aquellos aleatorizados, 142 con encuestas parcialmente completas se analizaron para determinar el sesgo de selección y la aceptabilidad, y 95 con encuestas completas se analizaron para determinar la validez de la encuesta.Los pacientes recibieron un reservorio en J, anastomosis latero-terminal o anastomosis termino-terminal.El estudio evaluó medidas de validez de la encuesta, como el Alfa de Cronbach estandarizado para la consistencia interna y los coeficientes de correlación de Spearman para la validez de construcción, la validez de convergencia y la capacidad de respuesta. Se utilizaron análisis univariados para evaluar la validez discriminativa.Se obtuvo suficiente aceptabilidad, construcción, validez de convergencia, y capacidad de respuesta. Todos los puntajes mostraron una gran consistencia interna (alfa de Cronbach0.8). Una capacidad discriminativa superior fue demostrada por diferencias significativas (p0.05) en dos de siete puntajes entre grupos de tratamiento neoadyuvante, y en seis de siete puntajes entre grupos de complicaciones, ninguno de los cuales fue detectado por SF-12 o FACT-C.Las limitaciones incluyeron un tamaño de muestra pequeño, diferencias culturales y la falta de evaluación de la confiabilidad test-retest del cuestionario.El Cuestionario de Calidad de Vida en Cáncer Colorrectal de Cleveland Clinic es una medida de calidad de vida eficiente y confiable que incorpora mejor factores específicos asociados a la cirugía de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B155.

Resume Environ 15 % des patients atteints de la polypose adenomateuse familiale « PAF » developpent au cours de leur vie une ou plusieurs tumeurs desmoides. Il s’agit des tumeurs mesenchymateuses benignes a agressivite locale sans potentiel metastatique. La plupart sont la consequence d’une anomalie genetique sporadique du gene de la β catenine. Quand les tumeurs desmoides sont associees a la PAF, elles ne presentent pas de mutation somatique de ce gene. En effet, la PAF est une maladie a transmission autosomique dominante liee a une mutation germinale du gene APC, ce qui permet d’orienter les patients en consultation d’oncogenetique. Parfois, ils peuvent etre la premiere manifestation de cette maladie. L’association d’une polypose colorectale et de tumeurs desmoides avait permis de definir le syndrome Gardner. Dans un contexte de PAF, le diagnostic des tumeurs desmoides est radiologiquement evident mais il necessite d’une confirmation anatomopathologique. La prise en charge est aussi complexe que dans les cas sporadiques du fait de l‘heterogeneite de ces tumeurs et de l’absence de biomarqueurs predictifs de leur evolution. L’identification de facteurs pronostiques biologiques et cliniques permettrait de mieux selectionner les patients necessitant un traitement car la surveillance active est une option therapeutique valide. La particularite des tumeurs desmoides associees a la PAF reside dans leur localisation majoritairement intra-abdominale et leur risque de complication. Durant les dix dernieres annees, la chirurgie a beaucoup cede la place a des traitements conservateurs (chimiotherapie, inhibiteurs de tyrosine kinase) qui ont montre une efficacite avec une amelioration significative de la survie sans progression des patients.

In cases of anastomotic failure after colorectal (CRA) or coloanal anastomosis (CAA), revision of the anastomosis is an ambitious surgical option that can be proposed in order to maintain bowel continuity. Our aim was to assess postoperative morbidity, risk of failure and risk factor for failure in patients after CRA or CAA.All consecutive patients who underwent redo-CRA/CAA in our institution between 2007-2018 were retrospectively included. The success of redo-CRA/CAA was defined by the restoration of bowel continuity 12 months after the surgery.Two hundred patients (114 male: 57%) were analyzed. The indication for redo-CRA/CAA was chronic pelvic infection in 74 patients (37%), recto-vaginal or urinary fistula in 59 patients (30%), anastomotic stenosis in 36 patients (18%) and redo anastomosis after previous anastomosis takedown in 31 patients (15%). Twenty-three percent of the patients developed a severe postoperative complication. Anastomotic leakage was diagnosed in 39 patients (20%). One-year-success of the redo-CRA/CAA was obtained in 80% of patients. In multivariate analysis, only obesity was associated with redo-CRA/CAA failure (p = 0.042). We elaborated a pre-operative predictive score of success using the four variables: male sex, age 60 years, obesity and history of pelvic radiotherapy. The success of redo-CRA/CAA was 92%, 86%, 80% and 62% for a preoperative predictive score value of 0, 1, 2 and ≥3, respectively (p = 0.010).In case of failure of primary CRA/CAA, bowel continuity can be saved in 4 out of 5 patients by redo-CRA/CAA despite 23% suffering severe postoperative morbidity.

International audience; To evaluate whether systematic mesh implantation upon primary colostomy creation was effective to prevent PSH.Summary of background data: Previous randomized trials on prevention of PSH by mesh placement have shown contradictory results.Methods: This was a prospective, randomized controlled trial in 18 hospitals in France on patients aged ≥18 receiving a first colostomy for an indication other than infection. Participants were randomized by blocks of random size, stratified by center in a 1:1 ratio to colostomy with or without a synthetic, lightweight monofilament mesh. Patients and outcome assessors were blinded to patient group. The primary endpoint was clinically diagnosed PSH rate at 24 months of the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01380860.Results: From November 2012 to October 2016, 200 patients were enrolled. Finally, 65 patients remained in the no mesh group (Group A) and 70 in the mesh group (Group B) at 24 months with the most common reason for drop-out being death (n = 41). At 24 months, PSH was clinically detected in 28 patients (28%) in Group A and 30 (31%) in Group B [P = 0.77, odds ratio = 1.15 95% confidence interval = (0.62;2.13)]. Stoma-related complications were reported in 32 Group A patients and 37 Group B patients, but no mesh infections. There were no deaths related to mesh insertion.Conclusion: We failed to show efficiency of a prophylactic mesh on PSH rate. Placement of a mesh in a retro-muscular position with a central incision to allow colon passage cannot be recommended to prevent PSH. Optimization of mesh location and reinforcement material should be performed.

International audience; Background: The outbreak of coronavirus disease 2019 (COVID-19) infection has led to the reorganization of hospital care in several countries. The objective was to report the postoperative mortality after elective digestive resections in a nationwide cohort during the lockdown period.Methods: This analytic study was performed using a national billing database (the Programme de Médicalisation des Systèmes d’Informations). Patients who underwent elective digestive resections were divided in 2 groups: the lockdown group defined by hospital admissions between March 17 and May 11, 2020; and the control group, defined by hospital admissions during the corresponding period in 2019. Groups were matched on propensity score, geographical region, and surgical procedure. The primary outcome was the postoperative mortality.Results: The overall population included 15,217 patients: 9,325 patients in the control group and 5,892 in the lockdown group. The overall surgical activity was decreased by 37% during the lockdown period. The overall in-hospital mortality during the hospital stay was 2.7%. After matching and adjustment, no dif-ference in mortality between groups was reported (OR ¼ 1.05; 95% CI: 0.83e1.34; P ¼ .669). An asymptomatic COVID-19 infection was a risk factor for a 2-fold increased mortality, whereas a symp-tomatic COVID-19 infection was associated with a 10-fold increased mortality.Conclusion: Despite a considerable reduction in the surgical activity for elective digestive resections during the lockdown period, mortality remained stable on a nationwide scale in COVID-free patients. These findings support that systematic COVID-19 screening should be advocated before elective gastrointestinal surgery and that all efforts should be made to maintain elective surgical resection for cancer during the second wave in COVID-free patients.

International audience

A better understanding of pathological features and oncological survival in ypT0 rectal cancer after neoadjuvant chemoradiotherapy is required to improve patient selection criteria for rectal-preserving approach by local excision. Our aim was to define risk of lymph node metastasis and oncological outcomes in ypT0 rectal cancer after chemoradiotherapy and total mesorectal excision.All consecutive patients who underwent total mesorectal excision for a nonmetastatic rectal adenocarcinoma classified ypT0 after neoadjuvant chemoradiotherapy, with or without locoregional lymph node involvement (ypN+ or ypN-), in 14 French academic centers between 2002 and 2015 were included. Data were collected retrospectively. Overall and disease-free survival were explored.Among the 383 ypT0 patients, 6% were ypN+ (23/283). Before chemoradiotherapy, 86% (327/380) were staged cT3-T4 and 41% (156/378) were staged cN+. The risk of ypN+ did not differ between cT3-T4 and cT1-T2 patients (P = .345) or between cN+ and cN- patients (P = .384). After a median follow-up of 61.1 months, we observed 95% confidence interval (92%-97%) of 5-year overall survival and 93% confidence interval (91%-96%) of 5-year disease-free survival. In Cox multivariate analysis, overall survival was altered by intra-abdominal septic complications (hazard ratio = 2.53, confidence interval [1.11-5.78], P = .028). Regarding disease-free survival, ypN+ status and administration of adjuvant chemotherapy were associated with a reduced disease-free survival (P = .001 for both). cT3/T4 staging and cN+ staging did not modify overall survival (P = .332 and P = .450) nor disease-free survival (P = .862 and P = .124).The risk of lymph node metastasis and the oncological survival do not depend on the initial cT or cN staging in cases of ypT0 complete rectal tumor regression.

Immunotherapies are part of the therapeutic strategy in many cancers and are indicated for metastatic colorectal adenocarcinoma with loss of expression of MisMatch Repair system proteins or with microsatelite instability (dMMR/MSI) in the United States. The rate of pathological response to immunotherapy remains poorly documented, but several cases of complete or major pathological response have recently been described. We decided to report the case of a complete pathological response to immunotherapy of a dMMR/MSI colorectal adenocarcinoma in a 74-year-old patient, initially inoperable due to duodenal invasion. Three months after the introduction of immunotherapy, the patient developed drug-induced colitis that contraindicated further treatment. Histological examination of the subtotal colectomy specimen revealed no residual tumour cells. The patterns of tumour regression were mainly represented by colloid regression, infarctoid-type necrosis and a resorptive inflammatory reaction. Although the operative indications for patients with metastatic dMMR/MSI colorectal cancer treated by immunotherapy are still very limited, the number of such specimens is expected to increase rapidly. The management of these specimens, as well as the possibility of a complete histological response, must be known by pathologists who play a key role in the pathophysiological knowledge of these lesions.

International audience; Background: After a failure of a colorectal or coloanal anastomosis, redo anastomotic surgery aims to avoid the risk of permanent stoma but, overall, to provide a satisfactory functional result and quality of life. Very limited data exist regarding the long-term results after a successful redo anastomosis. The present study aimed to report the long-term functional outcomes and quality of life in patients after a successful redo colorectal anastomosis or coloanal anastomosis.Methods: Between 2007 and 2018, all patients who had a successful restoration of bowel continuity after a failed primary anastomosis performed for a rectal cancer were included. Functional outcomes and quality of life were assessed using the low anterior rectal syndrome score and the Gastrointestinal Quality of Life Index.Results: One hundred and twenty-seven patients were eligible for inclusion in this study, with long-term functional outcomes assessed in 73 patients (57%). After a median follow-up of 69 months, 31 patients presented no or minor low anterior rectal syndrome (42%), whereas 31 patients reported a major low anterior rectal syndrome (42%). A definitive stoma was confectioned in 11 patients (15%), despite the technical success of redo anastomosis due to poor functional results. Only operative interval

Although duodenal adenomas and cancer appear to occur significantly less frequently in autosomal recessive MUTYH-associated polyposis (MAP) than in autosomal dominant familial adenomatous polyposis (FAP),1 current guidelines recommend similar endoscopic surveillance for both disorders.2-4 This involves gastro-duodenoscopy starting at 25 to 35 years of age and repeated at intervals determined by Spigelman staging based on the number, size, histological type and degree of dysplasia of adenomas, and by ampullary staging. Case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced Spigelman stage benign disease and even without coexisting adenomas.1 Recent molecular analyses suggest thatMAPduodenal adenomashave a higher mutational burden than FAP adenomas and are more likely to harbor oncogenic drivermutations, such as those in KRAS.5 These apparent differences in the biology and natural history of duodenal polyposis in FAP and MAP challenge the assumption that the same surveillance should be applied in both conditions.

Subtotal colectomy (STC) is performed for severe acute and refractory colitis. The diagnosis can be difficult even after the surgery when colectomy specimen has overlapping features of ulcerative colitis (UC) and Crohn’s disease (CD). The aim of this study was to evaluate the rate of postoperative diagnostic revision to CD after surgery and determine predictor factors. Retrospective study of 110 patients who underwent STC (2005–2018). Preoperative diagnosis comprised UC = 80 (73%), CD = 11 (10%), and unclassified colitis (IBDU = 19, 17%). Initial diagnosis of IBDU and UC was modified to CD in 6 patients (6%) after STC. The final diagnosis after the follow-up of 10 ± 6 years switched from CD for 8 patients (9%). The multivariate analysis showed that patients with a colitis evolving for less than 10 years and initial diagnosis of IBDU were the two independent factors associated with an increased risk of diagnosis change to CD (p = 0.03; p = 0.016). At the end of the follow-up, 15 patients (14%) had a definitive stoma. In patients with IBD, attention must be paid to determine the right restorative strategy to patients with an evolution of the disease less than 10 years or with IBDU who are more at risk to have a diagnosis change to CD after STC.

Summary Aim of the study Evaluate the impact of social deprivation on morbidity and mortality in surgery for colorectal cancer. Methods The COINCIDE prospective cohort included nearly 2,000 consecutive patients operated on for colorectal cancer at the Assistance Publique-Hospitals of Paris (AP-HP) from 2008 to 2010. The data on these patients were crossed with the PMSI administrative database. The European Social Deprivation Index (EDI) was calculated for each patient and classified into five quintiles (quintiles 4 and 5 being the most disadvantaged patients). Thirty-day post-operative morbidity was determined according to the Dindo-Clavien classification, with a Had®Hoc re-analysis of each file. Statistical analysis was performed using the proprietary Q-finder® algorithm. Results One thousand two hundred and fifty nine curative colorectal resections were analyzed. Mortality was 2.7% and severe morbidity (Dindo-Clavien ≥ 3) occurred in 16.4%. Mortality was not statistically significantly increased among the most disadvantaged who made up almost two thirds of the population (64.2%). Patients in quintiles 4 and 5 had a statistically significant increase in severe morbidity. The relative risk remained 1.5 even after adjustment for the known risk factors found in the analysis: age > 70 years, ASA score, urgency, and laparotomy. Conclusions The EDI represents an independent risk factor for severe morbidity after carcinologic colorectal resection. This study suggests that the determinants of health are multidimensional and do not depend solely on the quality and performance of the care system. The inclusion of this index in our surgical databases is therefore necessary, as is its use in health policy for the distribution of resources.

Resume But du travail Evaluer l’impact de la deprivation sociale sur la morbi-mortalite en chirurgie colorectale carcinologique. Methodes La cohorte prospective COINCIDE a inclus de 2008 a 2010 pres de 2000 patients consecutifs operes d’un cancer colorectal, a l’AP–HP. Cette base etait croisee avec la base administrative PMSI. L’index europeen de defavorisation sociale (EDI) etait calcule pour chaque patient et classe en 5 quintiles (les quintiles 4 et 5 etant les patients les plus defavorises). La morbidite postoperatoire etait determinee a 30 jours selon la classification Dindo-Clavien, avec une re-analyse ad hoc de chaque dossier. L’analyse statistique etait realisee via l’algorithme proprietaire Q-finder®. Resultats Au total, 1259 resections colorectales a visee curative etaient analysees. La mortalite etait de 2,7 % et la morbidite severe (Dindo ≥ 3) de 16,4 %. La mortalite n’etait pas significativement augmentee chez les plus defavorises (Pres de 2/3 de la population [64,2 %]). La morbidite severe etait significativement correlee aux quintiles 4 et 5. Ce risque restait multiplie par 1,5 apres ajustement sur les facteurs de risques connus et retrouves dans l’analyse : âge > 70 ans, score ASA, urgence, et laparotomie. Conclusions L’EDI represente un facteur independant de risque de morbidite severe apres resection colorectale carcinologique. Cette etude suggere que les determinants de la sante sont multidimensionnels et ne relevent pas uniquement de la seule performance du systeme de soins. L’inclusion de cet indice dans nos bases de donnees chirurgicales est donc necessaire, tout comme son utilisation en politique de sante pour la repartition des ressources.

International audience; Purpose : The reduction of length of hospitalization without compromising the patient's safety constitutes the challenge of the enhanced recovery after surgery (ERAS) programs. Our aim was to evaluate the feasibility and safety of a 3-day hospitalization after colectomy and 5-day hospitalization after proctectomy in the setting of an ERAS program. Methods : An ERAS program was prospectively proposed to all patients who required a colorectal resection (January 2014-December 2018) with a 3- or 5-day discharge objective. The success of the program was defined by a 3-/5-day hospitalization without complications and without readmissions.Results : Among 283 patients included, 232 patients had a colectomy (82%) and 51 (18%) patients a proctectomy. Eighty-six patients experienced complications (30%) including fifteen severe complications (5%). Mean hospital stay was 5.1 ± 3.7 (2-33) days. A total of 136 patients (48%) were discharged at 3-/5-day, within 9 were readmitted (3%). Discharge was delayed after 3-/5-day for complications (n = 65, 23%), CRP > 120 (n = 45, 16%) or refusal without medical reason (n = 37, 13%). The success rate of the program was 45% (n = 127). This success rate was similar between colectomy and proctectomy (p = 0.277) and between right and left colectomy (p = 0.450). In multivariate analysis, predictive factors associated with the program success were intraoperative use of lidocaine (OR 2.1 [1.1-4.1], p = 0.022), time to remove perfusion ≤ 2 days (OR 10.3 [5.4-19.6], p = 0.001), time to recover bowel movement ≤ 2 days (OR 4.0 [1.7-9.6], p = 0.002) and time to walk out of the room ≤ 2 days (OR 2.6 [1.1-6.0], p = 0.022).Conclusion : Integrating a realistic hospitalization duration objective into an ERAS program guarantees its safety, feasibility and effectiveness in reducing hospitalization duration.

International audience; Purpose: Perineal hernia (PH) is a tardive complication following abdomino-perineal resection (APR). Many repair methods are described and evidences are lacking. The aim of this study was to report PH management, analyze surgery outcomes and review the available literature.Methods: We retrospectively included all consecutive PH repair after APR performed between 2001 and 2017. We recorded data on APR surgery, PH symptoms and repair, and follow-up (recurrence and morbidity). Literature review included published articles on PubMed between 1960 and 2017.Results: 24 PH repairs were included. The approach was perineal N = 16, abdominal N = 5 and combined N = 3. A biological mesh was used for 17, a synthetic for 5 and a flap for 2 patients. The median follow-up was 25 months. Overall morbidity was 37.5% (N = 9): 37.5% for the perineal, 20% for the abdominal, and 66.7% for the combined approach. Complications occurred in 35.3% of biological and 20% of synthetic mesh repairs. Recurrence rate was 41.7%, similar for biological (n = 8, 47.1%) and synthetic meshs (n = 2; 40%). No recurrence occurred in the flap group. Depending of the approach, we found 50% for perineal (n = 8) and 40% of the abdominal cohort (N = 2). Among twelve studies, recurrence rates ranged from 0 to 66.7%. Abdominal or laparoscopic approach with synthetic mesh was associated with less recurrences (0 and 12.5% respectively) and complications (37.5% and 9.5%).Conclusions: Recurrences following PH repair are high irrespective of the repair technique. More studies are necessary to identify PH risk factors and decide the appropriate perineal reconstruction.

Aim Few studies have been published on erectile function after ileal pouch-anal anastomosis (IPAA) and, unlike in women, male fertility after IPAA has never been assessed. The primary objective was to assess the impact of IPAA on erectile function. The secondary objective was to assess the impact of IPAA on male fertility. Methods All of the male patients who underwent IPAA in two university care centres between 2003 and 2017, aged 70 years or less at the time of operation, were included. Forty-eight per cent of the patients responded to the international index of erectile function, the Jorge-Wexner score and a fertility questionnaire. All demographic and perioperative data were prospectively collected. Fertility results were compared with those of a control group undergoing appendectomy, matched for age at the time of operation, desire for paternity and length of follow-up. Results One hundred and thirty-nine patients were included, among which 46 (33%) presented with erectile dysfunction and 14 (10%) with severe erectile dysfunction. Age older than 50 years (OR 0.27, 95% CI 0.12-0.62, P = 0.002) and rectal dissection performed by open surgery (OR 4.16, 95% CI 1.62-10.65, P = 0.003) were independent risk factors for erectile dysfunction. There was no infertility after IPAA compared with controls: indeed, 23 (16%) IPAA patients presented with pregnancy in their couple versus 27 (22%) controls (P = 0.29), whereas 36 (26%) IPAA patients and 34 (28%) controls (P = 0.80) expressed paternity desire. Conclusion A total laparoscopic approach, including rectal dissection, should be preferred to preserve erectile function. Male fertility is not impaired after IPAA.

International audience; Purpose: The aim of this study was to investigate the association between expression of insulin-like growth factor-1 receptor (IGF1R) and its ligand, IGF-II, and disease-free survival (DFS) in patients with stage III colon cancer (CC).Methods: In this retrospective study we included consecutive patients who underwent curative surgery for stage III CC. IGF1R and IGF-II/IGF2 status were evaluated in tumour samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Associations of markers with DFS were analysed using Cox proportional hazards models.Results: Hundred and fifty-one CC patients were included (median age, 66.6 years; female, 54.3%). Low levels of IGF1R and IGF-II protein expression were observed in 16.1% and 10.7% of the cases, respectively. No significant differences in clinicopathological characteristics between patients with tumours expressing low IGF1R or IGF-II protein levels and those with high levels were observed. A low IGF1R protein expression was found to be significantly associated with a shorter DFS (HR 3.32; 95% CI, 1.7-6.31; p = 0.0003), while no association was observed between IGF-II protein expression and DFS (HR 0.91; 95% CI, 0.28-2.96; p = 0.87). In a multivariate analysis, IGF1R protein status remained an independent prognostic factor for DFS (HR 2.73; 95% CI, 1.40-5.31; p = 0.003). Furthermore, we found that neither IGF1R nor IGF2 mRNA expression levels as measured by qRT-PCR correlated with the respective protein expression levels as assessed by immunohistochemistry. Neither of the mRNA expression levels was significantly associated with DFS.Conclusions: From our data we conclude that low IGF1R protein expression represents a poor prognostic biomarker in stage III colon cancer.

International audience; Background and objectives: It has been suggested that tumor deposits (TDs) may have a worse prognosis in rectal cancer compared with colonic cancer. The aim of this study was to assess TDs prognosis in rectal cancer.Methods: Patients who underwent total mesorectum excision for rectal adenocarcinoma (2011-2016) were included. A case-matched analysis was performed to assess the accurate impact of TDs for each pN category after exclusion of synchronous metastasis.Results: A total of 505 patients were included. TDs were observed in 99 (19.6%) patients, (pN1c = 37 [7.3%]). TDs were associated with pT3-T4 stage (P = .037), synchronous metastasis (P = .003), lymph node (LN) invasion (P = .041), vascular invasion (P = .001), and perineural invasion (P < .001). TD was associated with a worse 3-year disease-free survival (DFS) among pN0 (51.2% vs 79.8%; P < .001); pN1 patients (35.2% vs 70.1%; P = .004) but not among pN2 patients (37.5% vs 44.7%; P = .499). After matching, pN1c patients had a worse 3-year DFS compared with pN0 patients (58.6% vs 82.4%; P = .035) and a tendency toward a worse DFS among N1 patients (40.1% vs 64.2%; P = .153). DFS was worse when one TD was compared with one invaded LN (40.8% vs 81.3%; P < .001).Conclusion: In rectal cancer, TDs have a metastatic risk comparable to a pN2 stage which may lead to changes in adjuvant treatment.

International audience; Background: Restorative proctocolectomy with ileal-pouch-anal anastomosis is the standard treatment for patients with ulcerative colitis or familial adenomatous polyposis. This procedure has undergone many changes and varies in 1, 2, or 3 stages. A diverting ileostomy can be created with the aim of reducing the consequence of an anastomotic leakage; however, its use is still unknown.Method: The value of defunctioning ileostomy was studied in a population of 388 patients undergoing restorative proctocolectomy with ileal-pouch-anal anastomosis between 2005 and 2017. Leakage rate and postoperative morbidity were assessed. Patients were matched on a propensity score using the following criteria: American Society of Anesthesiologists score, body mass index, diagnosis, surgical approach, and year.Results: Two hundred and three ileal-pouch-anal anastomosis for ulcerative colitis and 185 for familial adenomatous polyposis were performed representing 165 1-stage (61.6%), 79 classic 2-stage, 74 modified 2-stage, and 70 3-stage procedures. Regardless of the surgical strategy adopted, there were no significant differences in postoperative morbidity (P = .416), leakage rate (P = .369), and reoperation (P = .237), whether a diverting ileostomy was performed or not. After propensity score matching, there was no significant difference in postoperative morbidity (P = .363), leakage rate (P = .247), or reoperation (P = .243). The rate of persistent ileostomy at 1 year was higher in cases of classic 2-stage or 3-stage procedures (P = .036).Conclusion: After propensity score matching, defunctioning ileostomy for ileal-pouch-anal anastomosis does not reduce leakage rate or postoperative morbidity, independent of the surgical strategy. Systematic ileostomy for ileal-pouch-anal anastomosis is probably not justified, and its place should be redefined in a randomized trial.

Local drainages can be used to manage leakage in select patients without peritonitis.The aim of this study was to evaluate the efficacy of drainage procedures in maintaining a primary low anastomosis after anastomotic leakage.A retrospective observational study was performed on a prospectively maintained database.The study was performed between 2014 and 2017 in a tertiary referral center.Patients undergoing rectal resections with either a colorectal or coloanal anastomosis with diverting stoma were identified. Anastomotic leakages requiring a radiological or transanal drainage without peritonitis were included.The primary outcome was the maintenance of the primary anastomosis after local drainage of an anastomotic leakage and stoma reversal.A low anastomosis for rectal cancer with diverting stoma was performed in 326 patients. A total of 77 anastomotic leakages (24%) occurred, of which, 6 (8%) required abdominal surgery, 17 (22%) were treated conservatively (medical management), and 54 (70%) were managed by drainage. Surgical transanal drainage was performed in 21 patients (39%), with radiologic drainage procedures performed in 33 patients (61%). The median interval between surgery and drainage was 13 days (range, 9-21 d). Five patients (9%) required emergency abdominal surgery. Twenty-seven patients (50%) did not require any additional intervention after drainage procedure, whereas 21 patients (39%) underwent redo anastomotic surgery. Forty-three patients (80%) had no stoma at the end of follow-up. Failure to maintain the primary anastomosis after local drainage was associated with increased age (p = 0.04), a pelvic per-operative drainage (p = 0.05), a drainage duration10 days (p = 0.002), the time between surgery and drainage15 days (p = 0.03), a side-to-end or J-pouch anastomosis (p = 0.04), and surgical transanal drainage (p = 0.03).The small sample size of the study was the main limitation.Local drainage procedures maintained primary anastomosis in 50% of cases after an anastomotic leakage. See Video Abstract at http://links.lww.com/DCR/B57. ¿PUEDE UN DRENAJE LOCAL SALVAR UNA ANASTOMOSIS COLORRECTAL O COLOANAL FALLIDA? UNA COHORTE PROSPECTIVO DE 54 PACIENTES: Los drenajes locales se pueden utilizar para controlar las fugas en pacientes seleccionados sin peritonitis.El objetivo de este estudio fue evaluar la eficacia de los procedimientos de drenaje, para mantener una anastomosis primaria baja, después de una fuga anastomótica.Se realizó un estudio observacional retrospectivo en una base de datos mantenida prospectivamente.El estudio se realizó entre 2014-2017, en un centro de referencia terciaria.Se identificaron pacientes sometidos a resecciones rectales con anastomosis colorrectal o coloanal y estoma de derivación. Se incluyeron fugas anastomóticas sin peritonitis, que requirieron drenaje radiológico o transanal.El resultado primario fue el mantenimiento de la anastomosis primaria, después del drenaje local de una fuga anastomótica y la reversión del estoma.Se realizó una anastomosis baja para cáncer rectal con estoma derivativo en 326 pacientes. Se produjeron 77 (24%) fugas anastomóticas, de las cuales 6 (8%) requirieron cirugía abdominal, 17 (22%) fueron tratadas de forma conservadora (tratamiento médico) y 54 (70%) fueron manejadas por drenaje. Se realizó drenaje transanal en 21 pacientes (39%) y procedimientos de drenaje radiológico en 33 pacientes (61%). La mediana del intervalo entre la cirugía y el drenaje fue de 13 días [9-21]. 5 (9%) pacientes requirieron cirugía abdominal de emergencia. Veintisiete (50%) pacientes no requirieron ninguna intervención adicional después del procedimiento de drenaje, mientras que 21 pacientes (39%) se sometieron a una reparación quirúrgica anastomótica. 43 pacientes (80%) no tuvieron estoma al final del seguimiento. El fracaso para mantener la anastomosis primaria después del drenaje local, se asoció con un aumento de la edad (p = 0.04), un drenaje pélvico preoperatorio (p = 0.05), una duración del drenaje10 días (p = 0.002), el tiempo entre la cirugía y el drenaje15 días (p = 0.03), anastomosis termino lateral o bolsa en J (p = 0.04) y drenaje quirúrgico transanal (p = 0.03).El pequeño tamaño de la muestra del estudio fue la principal limitación.Después de la fuga anastomótica, los procedimientos del drenaje local conservaron la anastomosis primaria en el 50% de los casos. Vea el Resumen del Video en http://links.lww.com/DCR/B57.

International audience; AIM: To compare the functional results and quality of life after delayed colo-anal anastomosis (DCAA) or immediate colo-anal anastomosis (ICAA) following redo rectal surgery.METHOD:Twenty-six patients with DCAA between 2014 and 2018 were studied retrospectively (group A). Two control groups were used: 26 ICAA after redo surgery (group B) and 52 colo-anal anastomosis (CAA) after anterior resection (group C). Control groups were matched for age, sex, pelvic radiotherapy and time to surgery. Low Anterior Resection Syndrome (LARS) and Gastrointestinal Quality of Life Index (GIQLI) scores were used to assess function and quality of life.RESULTS: The indications for surgery were comparable for groups A and B: anastomotic failure with chronic sepsis (38% vs 50%, P = 0.40), vaginal fistula (42% vs 42%, P = 1) and urinary fistula (20% vs 8%, P = 0.22) as well as the number of previous abdominal operations (1.3 ± 0.9 vs 1.1 ± 0.6, P = 0.19). The median LARS score in the first 2 years was 30 [interquartile range (IQR) 14-41] for group A, 23 (IQR 0-41) for group B and 22 (IQR 11-37) for group C. After 2 years, the median LARS score improved in each group [A, 21 (IQR 11-35); B, 18 (IQR 5-26); C, 13 (IQR 9-20)], but was still high in group A. There was a tendency toward more major LARS in group A than in group B (46% vs 27%; P = 0.149). There was no difference in the mean GIQLI score between groups A and B (120 ± 16 vs 117 ± 19; P = 0.53) at the end of the follow-up period. Time after stoma closure (< 2 years) and previous radiotherapy were risk factors for major LARS in all populations.CONCLUSION: ICAA should be the procedure of choice where possible in redo surgery as it has better functional outcomes

International audience; BackgroundPostoperative peritonitis (POP) following gastrointestinal surgery is associated with significant morbidity and mortality, with no clear management option proposed. The aim of this study was to report our surgical management of POP and identify pre- and perioperative risk factors for morbidity and mortality.MethodsAll patients with POP undergoing relaparotomy in our department between January 2004 and December 2013 were included. Pre- and perioperative data were analyzed to identify predictors of morbidity and mortality.ResultsA total of 191 patients required relaparotomy for POP, of which 16.8% required >1 reinterventions. The commonest cause of POP was anastomotic leakage (66.5%) followed by perforation (20.9%). POP was mostly treated by anastomotic takedown (51.8%), suture with derivative stoma (11.5%), enteral resection and stoma (12%), drainage of the leak (8.9%), stoma on perforation (8.4%), duodenal intubation (7.3%) or intubation of the leak (3.1%). The overall mortality rate was 14%, of which 40% died within the first 48 h. Major complications (Dindo–Clavien > 2) were seen in 47% of the cohort. Stoma formation occurred in 81.6% of patients following relaparotomy. Independent risk factors for mortality were: ASA > 2 (OR = 2.75, 95% CI = 1.07–7.62, p = 0.037), multiorgan failure (MOF) (OR = 5.22, 95% CI = 2.11–13.5, p = 0.0037), perioperative transfusion (OR = 2.7, 95% CI = 1.05–7.47, p = 0.04) and upper GI origin (OR = 3.55, 95% CI = 1.32–9.56, p = 0.013). Independent risk factors for morbidity were: MOF (OR = 2.74, 95% CI = 1.26–6.19, p = 0.013), upper GI origin (OR = 3.74, 95% CI = 1.59–9.44, p = 0.0034) and delayed extubation (OR = 0.27, 95% CI = 0.14–0.55, p = 0.0027).ConclusionMortality following POP remains a significant issue; however, it is decreasing due to effective and aggressive surgical intervention. Predictors of poor outcomes will help tailor management options.

The high morbidity rates reported might influence surgeons’ decisions of whether to perform Hartmann’s reversal (HR). Our aim was to report the results of HR after “primary” Hartmann’s procedure (HP) or in redo surgery for failed anastomosis. All patients operated between 2007 and 2015 were included. Data and postoperative course were obtained from a review of medical records and databases. One hundred fifty patients (age 60, range (20–91) years, 62% male) were included. Eighty-six patients (57%) were ASA ≥ 2. HP was mostly performed for diverticulitis (29.3%) and anastomotic leakage (24%). HR was possible in 145(97%) patients including six with previous failed attempt. Overall morbidity was 22.7% including 11.7% severe complications (Dindo 3–4). Operative blood loss and Charlson comorbidity index were the only significant risk factor for postoperative pelvic complications (p = 0.03; p = 0.0002, respectively). In a colorectal tertiary center, HR was feasible in 97% with a low morbidity and a 3.4% anastomotic leakage rate.

Regular follow-up for patients with Lynch syndrome (LS) is vital due to the increased risk of colorectal (50–80%), endometrial (40–60%), and other cancers. However, there is an ongoing debate concerning the best interval between colonoscopies. Currently, no specific endoscopic follow-up has been decided for LS patients who already have an index colorectal cancer (CRC). The aim of this study was to evaluate the risk of metachronous cancers (MC) after primary CRC in a LS population and to determinate if endoscopic surveillance should be more intensive. A prospective cohort of patients with a confirmed diagnosis of hereditary CRC since 2009 was included. Patients with LS and a primary CRC were the cohort of choice. One hundred twenty-one patients were included with a median age of 44 years(16–70). At least one MC occurred in 39 patients (32.2%), with a median interval of 67 months (6–300) from index cancer. Fifteen (38.5%) developed two or more MCs during follow-up, with a median number of two (2–6) tumors occurring. Metachronous CRC were diagnosed after a median interval of 24 (6–57) months since last colonoscopy and were more commonly seen in MSH2 mutation carriers (58 vs. 35%, p = 0.001). After a median follow-up of 52.9 (3–72) months, no cancer-related deaths were recorded. Patients with LS have an increased risk of MC, especially CRCs. With a median time period of 24 months between colonoscopy and metachronous CRC, the interval between surveillance colonoscopies following primary CRC should not exceed 18 months, especially in patients with MSH2 mutation.

Background & Aims Recent studies have shown that cancers arise as a result of the positive selection of driver somatic events in tumor DNA, with negative selection playing only a minor role, if any. However, these investigations were concerned with alterations at nonrepetitive sequences and did not take into account mutations in repetitive sequences that have very high pathophysiological relevance in the tumors showing microsatellite instability (MSI) resulting from mismatch repair deficiency investigated in the present study. Methods We performed whole-exome sequencing of 47 MSI colorectal cancers (CRCs) and confirmed results in an independent cohort of 53 MSI CRCs. We used a probabilistic model of mutational events within microsatellites, while adapting pre-existing models to analyze nonrepetitive DNA sequences. Negatively selected coding alterations in MSI CRCs were investigated for their functional and clinical impact in CRC cell lines and in a third cohort of 164 MSI CRC patients. Results Both positive and negative selection of somatic mutations in DNA repeats was observed, leading us to identify the expected true driver genes associated with the MSI-driven tumorigenic process. Several coding negatively selected MSI-related mutational events (n = 5) were shown to have deleterious effects on tumor cells. In the tumors in which deleterious MSI mutations were observed despite the negative selection, they were associated with worse survival in MSI CRC patients (hazard ratio, 3; 95% CI, 1.1–7.9; P = .03), suggesting their anticancer impact should be offset by other as yet unknown oncogenic processes that contribute to a poor prognosis. Conclusions The present results identify the positive and negative driver somatic mutations acting in MSI-driven tumorigenesis, suggesting that genomic instability in MSI CRC plays a dual role in achieving tumor cell transformation. Exome sequencing data have been deposited in the European genome–phenome archive (accession: EGAS00001002477)., Graphical abstract

But La chimiotherapie perioperatoire est le traitement de reference des adenocarcinomes gastriques > T1b. L’objectif etait d’evaluer l’interet de la chimiotherapie adjuvante (CTadj) chez les bons repondeurs a la chimiotherapie neoadjuvante (CTneoadj). Methodes A partir de la cohorte multicentrique francophone de l’AFC de 2131 patients, pris en charge pour un adenocarcinome gastrique entre 2007 et 2017, les patients non metastatiques ayant recu une CTneoadj (n = 762) ont ete analyses. Parmi eux, nous nous sommes interesses au groupe de patients en reponse quasi-complete (RQC), definie par un stade ypT0, ypTis, ypT1-ypN0. L’objectif principal etait la survie sans recidive a 5 ans. Resultats Au total, 135 patients etait RQC (17,7 %) dont 40 en reponse complete ypT0N0 (5,3 %). Les facteurs predictifs de RQC etaient : une localisation antro-pylorique, un stade pretherapeutique ≤ cT2, une tumeur bien differenciee, ≥ 2 cycles de CTneoadj, un type intestinal ou mixte (classification de Lauren), et l’absence de cellule independante. Parmi les RQC, 85 patients (63 %) ont debute une CTadj (CTadj+) et 50 patients (37 %) non (CTadj−). Les patients CTadj− etaient significativement plus âges et avaient plus frequemment des complications postoperatoires severes (≥ grade 3a Dindo–Clavien). Les taux de survie globale (SG) et sans recidive (SSR) a 5 ans etaient similaires entre CTadj+ et CTadj− (respectivement 92 % vs 82 % ; 89 % vs 83 %). Parmi les CTajd+, une toxicite severe etait notee chez 11 patients (13 %). Conclusion La realisation d’une CTadj chez les patients ypT0-1N0 apres CTneoadj ne semble pas apporter de benefice de SG ou SSR, au prix d’une toxicite non negligeable.

International audience; Background: Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs.Patients and methods: MSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation. Sporadic cases were molecularly defined as those displaying MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no MMR germline mutation.Results: Among 129 MSI/dMMR mCRC patients, 81 (63%) were LS-like and 48 (31%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would have been misclassified using an algorithm based on local medical records (age, Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate analysis, parameters associated with better overall survival were age (P < 0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival, but not LS. LS-like patients were associated with more frequent liver involvement, metastatic resection and better disease-free survival after metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first-line chemotherapy was similar between the two groups (4.2 and 4.2 months; P = 0.44).Conclusions: LS-like and sporadic MSI/dMMR mCRCs display distinct natural histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular whether immune checkpoint inhibitors efficacy differs in these two populations.

Harnessing the immune system to fight tumor cells is becoming a promising and innovative therapeutic strategy for a large spectrum of malignancies. The evaluation of immunotherapy in the context of colorectal cancers (CRCs) has brought to light mismatch repair deficiency as a major predictive biomarker for the efficacy of immune checkpoint blockade. In this review, we summarize the promising results of immune checkpoint inhibitors for patients with metastatic CRCs harboring mismatch repair deficiency, with special emphasis on further clinical development. Given the biological determinants of sensitivity to immune checkpoint blockade, we will also elucidate points that could unlock the potential of immunotherapy for patients with mismatch repair-proficient CRC.