Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR).

INTRODUCTION: This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS: EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

Intracorporeal versus extracorporeal anastomosis in laparoscopic right hemicolectomy: results from the CLIMHET study group.

BACKGROUND: Laparoscopic right hemicolectomy (LRHC) is increasingly performed for the treatment of right colon disease. Nevertheless, standardization of the surgical technique regarding the performance of intracorporeal (IC) or extracorporeal (EC) anastomosis is lacking. The purpose of this study was to compare short-term postoperative outcomes in patients who had laparoscopic right colectomy either with IC or EC. METHODS: This was a retrospective, non-randomized and multicenter study conducted from January 2005 to December 2015 on the CLIMHET study group cohort from five tertiary centers in France. Data were collected for all patients with LRHC to compare patient characteristics, intraoperative data and postoperative outcomes in terms of medical and surgical complications, duration of hospitalization and mortality. A multivariate analysis was performed to compare the results in the two groups. RESULTS: Of the 597 patients undergoing LRHC, 150 had IC and 447 had EC. The incidence of medical complications (cardiac, vascular, and pulmonary complications) was lower in the IC group than in the EC group (13 vs 20%, p = 0.049). This difference remained significant in multivariate analysis after adjusting to field characteristics and patient histories (p = 0.009). Additionally, a shorter hospital stay (7 vs 8 days, p = 0.003) was observed in the IC group as compared to the EC group. This difference remained significant in favor of the IC group in multivariate analysis (p = 0.029). There was no difference between the groups as regards: surgical complications (p = 0.76), time of mobilization (p = 0.93), reintervention rate (p = 1) and 90-day mortality (p = 0.47). CONCLUSIONS: Our results show that IC anastomosis in LRHC is associated with fewer medical complications and shorter hospital stays compared to EC anastomosis.

Surgical management of gastric adenocarcinoma. Official expert recommendations delivered under the aegis of the French Association of Surgery (AFC).

Gastric adenocarcinoma (GA) is the 5th most common cancer in the world; in France, however, its incidence has been steadily decreasing. Twenty-five experts brought together under the aegis of the French Association of Surgery collaborated in the drafting of a series of recommendations for surgical management of GA. As concerns preoperative evaluation and work-up, echo-endoscopy aimed at clarifying lymph node status should be performed in all candidates for surgical resection and exploratory laparoscopy in cases of GA cT3/T4 and/or N+ for peritoneal carcinomatosis. On the other hand, PET-scan should not be performed systematically, but only when the other modalities for diagnosis prove insufficient. Laparotomy remains the route of choice to achieve total or partial gastrectomy with D2 lymph node lymphadenectomy for advanced lesions (>T2N0). To limit the risk of dumping syndrome and esophageal reflux and as a way of reestablishing continuity, construction of a jejunal pouch on Roux-en-Y following total gastrectomy is recommended. In cases of peritoneal carcinosis in GA with a low peritoneal cancer index (PCI) (<7) in a patient in good general condition whose disease is controlled by chemotherapy, macroscopically complete cytoreduction with intraperitoneal hyperthermal chemotherapy will probably be required, and it will have to take place in an expert center. Only in the event of Child A cirrhosis may gastrectomy with D2 lymphadenectomy be considered. Palliative gastrectomy or surgical bypass for distal stomach obstruction in a patient in good general condition may also be envisioned.

Long-term functional results and quality of life after redo rectal surgery: delayed versus immediate colo-anal anastomosis.

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.

The management of perineal hernia following abdomino-perineal excision for cancer.

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.

Operating room hygiene: Clinical practice recommendations.

INTRODUCTION: The French Society of Gastro-Intestinal Surgery (SociétéFrançaisedeChirurgieDigestive) and the Association of hepato-bilio-pancreatic and transplantation surgery (AssociationdeChirurgieHépato-Bilio-PancréatiqueetTransplantation) requested that clinical practice recommendations be established with regard to operating room hygiene. METHODS: The literature was analyzed according to the High Authority of Health (HauteAutoritédesanté [HAS]) methodology and after consultation of the Cochrane and Medline databases. Pertinent references were selected, and supplementary references were hand-picked from the reference lists. Only English or French language papers were retained. The recommendations of learned societies and the World Health Organization were also considered. RESULTS: Recommendations were proposed with regard to pre-operative patient preparation, skin preparation, draping, wound edge protectors, surgeon hygiene, wound closure, and operating room environment. CONCLUSION: These clinical practice recommendations should guide and improve the daily practice of gastro-intestinal surgeons.

Correction to: Laparoscopic Hyperthermic Intraperitoneal Chemotherapy for Patients with Gastric Peritoneal Metastases: Limitations and Perspectives.

The title of this paper is corrected as reflected here.

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

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

Surgical management of obstructive left colon cancer at a national level: Results of a multicentre study of the French Surgical Association in 1500 patients.

PURPOSE: Surgical management of obstructive left colon cancer (OLCC) is controversial. The objective is to report on postoperative and oncological outcomes of the different surgical options in patients operated on for OLCC. METHODS: From 2000-2015, 1500 patients were treated for OLCC in centers members of the French Surgical Association. Colonic stent (n=271), supportive care (n=5), palliative derivation (n=4) were excluded. Among 1220 remaining patients, 456 had primary diverting colostomy (PDC), 329 a segmental colectomy (SC), 246 a Hartmann's procedure (HP) and 189 a subtotal colectomy (STC) as first-stage surgery. Perioperative data and oncological outcomes were compared retrospectively. RESULTS: There was no difference between the 4 groups regarding gender, age, BMI and comorbidities. Postoperative mortality and morbidity were 4-27% (PDC), 6-47% (SC), 9-55% (HP), 13-60% (STC), respectively (P=0.005). Among the 431 living patients after PDC, 321 (70%) patients had their primary tumour removed. Cumulative mortality and morbidity favoured PDC (7-39%) and SC (6-40%) compared to HP (1-47%) and STC (13-50%) (P=0.04). At the end of follow-up definitive stoma rates were 39% (HP), 24% (PDC), 10% (SC), and 8% (STC) (P<0.0001). Five-year overall and disease-free survival was: SC (67-55%), PDC (54-48%), HP (54-37%) and STC (48-49%). After multivariate analysis, SC and PDC were associated with better prognosis compared to HP and STC. CONCLUSION: In OLCC, SC and PDC are the two preferred options in patients with good medical conditions. For patients with severe comorbidities PDC should be recommended, reserving HP and STC for patients with colonic ischaemia or perforation complicating malignant obstruction.

Thirty-day mortality after emergency surgery for obstructing colon cancer: survey and dedicated score from the French Surgical Association.

AIM: The aim was to define risk factors for postoperative mortality in patients undergoing emergency surgery for obstructing colon cancer (OCC) and to propose a dedicated score. METHOD: From 2000 to 2015, 2325 patients were treated for OCC in French surgical centres by members of the French National Surgical Association. A multivariate analysis was performed for variables with P value ≤ 0.20 in the univariate analysis for 30-day mortality. Predictive performance was assessed by the area under the receiver operating characteristic curve. RESULTS: A total of 1983 patients were included. Thirty-day postoperative mortality was 7%. Multivariate analysis found five significant independent risk factors: age ≥ 75 (P = 0.013), American Society of Anesthesiologists (ASA) score ≥ III (P = 0.027), pulmonary comorbidity (P = 0.0002), right-sided cancer (P = 0.047) and haemodynamic failure (P < 0.0001). The odds ratio for risk of postoperative death was 3.42 with one factor, 5.80 with two factors, 15.73 with three factors, 29.23 with four factors and 77.25 with five factors. The discriminating capacity in predicting 30-day postoperative mortality was 0.80. CONCLUSION: Thirty-day postoperative mortality after emergency surgery for OCC is correlated with age, ASA score, pulmonary comorbidity, site of tumour and haemodynamic failure, with a specific score ranging from 0 to 5.

Immunomodulatory Activity of VEGF in Cancer.

The ability of tumor cells to escape tumor immunosurveillance contributes to cancer development. Factors produced in the tumor microenvironment create "tolerizing" conditions and thereby help the tumor to evade antitumoral immune responses. VEGF-A, already known for its major role in tumor vessel growth (neoangiogenesis), was recently identified as a key factor in tumor-induced immunosuppression. In particular, VEGF-A fosters the proliferation of immunosuppressive cells, limits T-cell recruitment into tumors, and promotes T-cell exhaustion. Antiangiogenic therapies have shown significant efficacy in patients with a variety of solid tumors, preventing tumor progression by limiting tumor-induced angiogenesis. VEGF-targeting therapies have also been shown to modulate the tumor-induced immunosuppressive microenvironment, enhancing Th1-type T-cell responses and increasing tumor infiltration by T cells. The immunomodulatory properties of VEGF-targeting therapies open up new perspectives for cancer treatment, especially through strategies combining antiangiogenic drugs with immunotherapy. Preclinical models and early clinical studies of these combined approaches have given promising results.

Cytoreductive surgery with a hyperthermic intraperitoneal chemotherapy program: Safe after 40 cases, but only controlled after 140 cases.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), used to treat peritoneal surface malignancies (PSM), is a complex procedure with significant major morbidity (MM). OBJECTIVE: To investigate the learning curve (LC) of CRS with HIPEC in a new specialized surgical unit with a fully trained senior surgeon and individualize the variables associated with morbidity and oncological results. METHODS: A total of 290 consecutive patients with PSM were included. Complete CRS with HIPEC was performed in 204 patients. A risk-adjusted sequential probability ratio test was used to assess the LC on the basis of rates of incomplete cytoreduction (IC) and MM. RESULTS: Complete CRS, MM, and mortality rates were 70.4%, 30.4%, and 2.5%, respectively. Tumor histotype, a high peritoneal cancer index (PCI) and the invaded region were the major independent risk factors for IC, whereas previous surgery, high PCI, stomia realization and blood transfusion were predictors of MM. RA-SPRT showed that 140 and 40 cases were needed to achieve the lowest risk of IC and MM, respectively. CONCLUSION: CRS with HIPEC to treat PSM has a steep LC. Drastic selection has to be made at the beginning, excluding high PCI, rare peritoneal disease and patients previously operated on.

Prognostic score for recurrence after Whipple's pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort.

BACKGROUND: Ampullary carcinoma (AC) is a relatively rare entity often managed as a biliopancreatic carcinoma. AC has a better prognosis than peri ampullary tumors after resection, but more than a third of patients relapse. Factors predictive of recurrence are controversial, mainly because the relevant studies are very small or also included non AC tumors. There are no guidelines on the use of adjuvant or neoadjuvant chemotherapy. The aim of this study was to identify prognostic factors for recurrence after AC resection in a large multicentric cohort, and to establish a simple, practical, predictive score for recurrence in order to guide multidisciplinary decisions. METHODS: We included 152 consecutive patients who underwent Whipple's pancreaticoduodenectomy for ampullary carcinoma from January 2000 to December 2010 in 10 gastrointestinal oncology departments. RESULTS: The estimated overall 5-year disease-free survival rate (DFS) was 47.1%. In multivariate analysis, age≥ 75 years at diagnosis (p < 0.0001), poor general condition (p = 0.01), poorly (p = 0.005) or moderately differentiated tumors (p = 0.01) and TNM stage IIb or III (p = 0.05) were associated with poor DFS. Based on this multivariate analysis, we developed a prognostic score with three levels of risk: DFS at 5 years was 73.5% in the low-risk group and 20.1% in the high-risk group. CONCLUSION: This simple score based on age, general condition, tumor differentiation and TNM stage can classify patients into subgroups with different risks of recurrence and could help with therapeutic decisionmaking.

Hyperthermic isolated liver perfusion with melphalan and bevacizumab.

Whereas surgical resection is the only curative treatment for liver tumors, effective treatment for isolated unresectable lesions when there is tumor progression in spite of several lines of chemotherapy remains to be found. We report herein two cases of patients treated by a 1-hour Hyperthermic Isolated Liver Perfusion (HILP) with a combination of melphalan and bevacizumab leading to complete response. The first patient had liver metastases secondary to previously resected malignant glucagonoma and the second, recurrent hepatocellular carcinoma. We used bevacizumab in association with melphalan for HILP because of the additional effect of an anti-VEGF antibody in these highly vascularized tumors and its locally restricted delivery to the isolated hepatic vascular compartment despite of its classic contraindication in association with surgery. The protocol was approved by the Ethics Committee. Enhanced CT scans during follow-up showed complete tumor necrosis as early as the second postoperative day. Patients had 27 and 7 months disease-free survival and 48 and 41 months overall survival after HILP, for neuroendocrine liver metastases and HILP plus liver transplantation for HCC respectively. Under very specific conditions, bevacizumab in HILP can provide excellent tumor response in hopeless clinical cases of liver tumors.