Association between polyunsaturated fatty acids in adipose tissue and mortality of colorectal cancer patients.

INTRODUCTION: Nutritional intake and dysregulation of fatty acid metabolism play a role in the progression of various tumors, but the consumption of fatty acids is difficult to assess accurately with dietary questionnaires. Biomarkers can objectively assess intake, storage and bioavailability. OBJECTIVE: We studied the association between the polyunsaturated fatty acid (PUFA) composition of abdominal subcutaneous adipose tissue (good indicator of dietary intake over 2-3 years) and all-cause mortality. METHODS: In the multicenter AGARIC study, samples from 203 patients with colorectal cancer (CRC) undergoing curative surgery, were harvested from subcutaneous adipose tissue, which were then analyzed for PUFA composition. RESULTS: After a median follow-up of 45 months, 76 patients died. These patients were more often men (72.4% versus 57.5%, P = 0.04), diabetic (32.9% versus 13.4%, P = 0.001), old (median: 74.5 versus 66.6 years, P < 0.001) and with high alcohol consumption (47.4% versus 30.7%, P = 0.005). An increased risk of death was observed with higher levels of 20:2 ω-6 (hazard ratiotertile3 vstertile1 (HRT3vsT1) 2.12; 95% confidence interval (CI) 1.01-4.42; p-trend = 0.04), 22:4 ω-6 (HRT3vsT1 = 3.52; 95% CI = 1.51-8.17; p-trend = 0.005), and 22:5 ω-6 (HRT3vsT1 = 3.50; 95% CI = 1.56-7.87; p-trend = 0.002). Conversely, the risk of death seemed lower when higher concentrations of 18:3 ω-6 (HRT3vsT1 = 0.52; 95% CI = 0.27-0.99; p-trend = 0.04) and the essential fatty acid, α-linolenic acid 18:3 ω-3 (HRT3vsT1 = 0.47; 95% CI = 0.24-0.93; p-trend = 0.03) were observed. CONCLUSION: The risk of death was increased in CRC patients with higher concentrations of certain ω-6 PUFAs and lower concentrations of α-linolenic acid in their subcutaneous adipose tissue. These results reflect dietary habits and altered fatty acid metabolism. Our exploratory results warrant confirmation in larger studies with further exploration of the mechanisms involved.

Does intraperitoneal mesh increase the risk of bowel obstruction? A nationwide French analysis.

INTRODUCTION: Incisional hernias are associated with a reduced quality of life. Mesh reinforcement of the abdominal wall is the current standard for incisional hernia repair (IHR), since it reduces the risk of recurrence. The best position for the mesh remains controversial, and each position has advantages and disadvantages. OBJECTIVE: In this nationwide population-based study, we aimed to determine whether IHR with intraperitoneal mesh is associated with an increased risk of bowel obstruction. PATIENTS AND METHODS: Using the French hospital database (PMSI), which collects data from all public and private hospitals, two patient cohorts were created and compared. Patients having undergone a laparoscopic IHR with intraperitoneal mesh (IPOM) in 2013 or 2014 due to a laparotomy performed in the 4 previous years were the IPOM group. Patients hospitalized for any other acute disease (i.e., without IHR) in 2013 and 2014, but having a similar laparotomy in the 4 previous years were the control group. Both cohorts were followed until 2019 in search of any episode of bowel obstruction. RESULTS: A total of 815 patients were included in the IPOM group and matched to 1630 control patients. The 5 year bowel obstruction rate was 7.36% in the IPOM group and 4.42% in the control group (p < 0.01). In the multivariate analysis, after adjustment on age and obesity, incisional hernia repair with laparoscopic IPOM increased the risk of bowel obstruction in the 5 years following surgery (HR = 1.712; 95% CI 1.208-2.427; p = 0.0025). CONCLUSIONS: Patients having undergone laparoscopic IPOM have an increased risk of bowel obstruction compared with patients who have a similar surgical history but no IHR.

Increased risk of colon cancer after acute appendicitis: a nationwide, population-based study.

Background: Acute appendicitis is the most common digestive disease requiring emergency surgery. Colorectal cancer is the third most common cancer in France. An increased risk of colorectal cancer after acute appendicitis has been suggested. We aimed to assess the frequency of hospitalization for colon cancer after appendicitis in a nationwide analysis. Methods: Using the French Hospital Discharge Database (PMSI), we included all patients aged 18-59 years presenting with acute appendicitis between 2010 and 2015. Univariate and multivariate analyses were performed to compare colon cancer occurrence in these patients vs a control-matched population with a hospital stay for trauma in the same period. Patients presenting strong risk factors for colorectal cancer were excluded. Findings: A total of 230,349 patients with acute appendicitis (exposed group) were included. We used a propensity score to match each exposed patient with two unexposed patients (controls) to ensure the comparability of the groups, resulting in a control group of 460,698 patients. Univariate analysis found significantly more colon cancer in the appendicitis group, especially during the first year after appendicitis (5 per 10,000 vs 1 per 10,000, p < 0.000, this corresponds to 111 patients in the appendicitis group), namely within the first 6 months. Survival analysis confirmed patients treated for appendicitis present a 4 times higher risk of being diagnosed with colon cancer than control patients during the first year of follow-up (sHR = 4.67 (95% CI: 3.51-6.21), and 8 times higher during the first 6 months (sHR = 8.39; 95% CI: 5.41-12.99). The association was even more marked for right-sided colon cancer (sHR = 8.25; 95% CI: 5.03-13.54 during the 1st year). While the risk of diagnosis of colon cancer was also significant for patients over 40 years, it was even greater in patients under 40 years, who had between a 6-fold and 12-fold increase in risk. Interpretation: In this population-based study, we found that acute appendicitis seems to be a warning sign for colon cancer (reverse causality) in both middle-aged and younger adults. The risk of presenting with cancer colon was higher during the first six months after acute appendicitis. This raises the issue of routine diagnostic work-up in adults presenting with acute appendicitis. Funding: Regional Council of Burgundy.

Primary Ventral Hernia Repair and the Risk of Postoperative Small Bowel Obstruction: Intra Versus Extraperitoneal Mesh.

OBJECTIVE: The aim of this study was to compare the likelihood of bowel obstruction according to the placement of the mesh (either intraperitoneal or extraperitoneal) in ventral hernia repairs. MATERIALS AND METHODS: Patients were divided into two groups, an intraperitoneal (IP) group (mesh placed by laparoscopy or with an open approach) and an extraperitoneal (EP) group, all operated on in the Digestive Surgery Department at the Dijon University Hospital. The primary outcome was the occurrence of an episode of bowel obstruction requiring hospitalization and confirmed by abdominal CT scan. RESULTS: Between March 2008 and July 2021, 318 patients were included, with 99 patients in the EP group (71 meshes placed preperitoneally and 28 placed retromuscularly) and 219 patients in the IP group (175 patients operated on laparoscopically versus 44 patients by direct approach). Three patients presented an episode of acute intestinal obstruction, with no difference between the two groups (p = 0.245), although all bowel obstructions occurred in the IP group and with the laparoscopic approach (1.7% of patients operated on by laparoscopy). The occlusive events occurred at 1 month, 2 years, and 3 years. There was no difference in terms of recurrence or postoperative chronic pain. There were more seroma and mesh infections in the EP group (p < 0.05). Two patients operated on by laparoscopy had undetected bowel injuries, prompting emergent surgery for peritonitis. CONCLUSIONS: No statistically significant difference was found in terms of bowel obstruction between the intraperitoneal and the extraperitoneal position, but all cases of obstruction happened in the intraperitoneal mesh group. Visceral lesions remain a major complication of the laparoscopic approach that should not be neglected.

Impact of hospital volume in liver surgery on postoperative mortality and morbidity: nationwide study.

BACKGROUND: This nationwide retrospective study was undertaken to evaluate impact of hospital volume and influence of liver transplantation activity on postoperative mortality and failure to rescue after liver surgery. METHODS: This was a retrospective study of patients who underwent liver resection between 2011 and 2019 using a nationwide database. A threshold of surgical activities from which in-hospital mortality declines was calculated. Hospitals were divided into high- and low-volume centres. Main outcomes were in-hospital mortality and failure to rescue. RESULTS: Among 39 286 patients included, the in-hospital mortality rate was 2.8 per cent. The activity volume threshold from which in-hospital mortality declined was 25 hepatectomies. High-volume centres (more than 25 resections per year) had more postoperative complications but a lower rate of in-hospital mortality (2.6 versus 3 per cent; P < 0.001) and failure to rescue (5 versus 6.3 per cent; P < 0.001), in particular related to specific complications (liver failure, biliary complications, vascular complications) (5.5 versus 7.6 per cent; P < 0.001). Liver transplantation activity did not have an impact on these outcomes. CONCLUSION: From more than 25 liver resections per year, rates of in-hospital mortality and failure to rescue declined. Management of specific postoperative complications appeared to be better in high-volume centres.

Early detection of anastomotic leak with C-reactive protein increases the chances of anastomotic salvage.

AIM: Anastomotic leak results in increased morbidity and affects functional and oncological outcomes after colectomy. Measurement of C-reactive protein (CRP) allows early detection of anastomotic leaks. The aim of this study was to evaluate the benefit to the patient of earlier diagnosis and management of anastomotic leaks, namely avoiding takedown of the anastomosis. METHOD: Patients with an anastomotic fistula after elective colorectal surgery from 2010 to 2020 were included. Three periods were defined according to progressive adherence to the CRP protocol in our department. A comparison was made between the periods 'before' (2010-2013) and 'after' (2016-2020) in terms of morbidity, mortality, anastomotic salvage, days spent in hospital within the first postoperative month, timely adjuvant chemotherapy and anastomotic stenosis. RESULTS: Out of 2655 elective colorectal operations, 171 patients presented with an anastomotic leak and 123 patients were included in the study. In univariate analysis, patients in the 'after' group had fewer severe complications (Clavien-Dindo Grade III to IV, 66.7% vs. 56.9; p = 0.017); the difference did not reach significance regarding timely postoperative chemotherapy (p = 0.058) and anastomotic stenosis (p = 0.682). In both, univariate and multivariate analysis, the 'after' period increased the chances of preserving the anastomosis (OR = 2.37 [1.08-5.17]) and increased the number of days out of hospital (p = 0.0002). CONCLUSION: A CRP-based protocol for the screening of anastomotic leaks after colorectal surgery was related to increased anastomotic conservation, a decreased impact and severity of the leak and a shorter length of hospital stay.

C-reactive protein identifies patients at low risk of anastomotic leak after esophagectomy.

PURPOSE: Fast-track protocols are increasingly used after digestive surgery. After esophagectomy, the gravity and the fear of anastomotic leak may be an obstacle to generalization of such protocols. C-reactive protein (CRP) might be a reliable tool to identify patients at low risk of anastomotic leak after esophagectomy, so that they can be safely included in a fast-track program. The aim of our retrospective bicentric study is to evaluate the interest of C-reactive protein measurement for the early diagnosis of anastomotic leak after esophagectomy. METHODS: Patients having undergone Ivor-Lewis procedure between January 2009 and September 2017 were included in this bicentric retrospective study. CRP values were recorded between postoperative day 3 (POD 3) and postoperative day 5 (POD 5). All postoperative complications were recorded, and the primary endpoint was anastomotic leak. RESULTS: We included 585 patients. Among them, 241 (41.2%) developed infectious complications and 69 patients (11.8%) developed anastomotic leak. CRP had the best predictive value on POD 5 (AUC = 0.74; 95% CI: 0.67-0.81). On POD 5, a cut-off value of 130 mg/L yielded a sensitivity of 87%, a specificity of 51%, and a negative predictive value of 96% for the detection of anastomotic leak. CONCLUSIONS: CRP may help in identifying patients at very low risk of anastomotic leak after esophagectomy. Patients with CRP values < 130 mg/L on POD 5 can safely undertake an enhanced recovery protocol.

Establishing Peer Consensus About the Use of Long-Term Biosynthetic Absorbable Mesh for Hernia (Grades 2-3) as the Standard of Care.

BACKGROUND: Standard synthetic and biologic meshes, often used in hernia repair, have commonly been used and each have their strengths but associated drawbacks. Long-term biosynthetic absorbable (LTBA) mesh has been developed to combine the strengths of synthetic and biologic meshes without the associated weaknesses. As a newer type of mesh, the supporting evidence base is still growing, and their optimum use has yet to be defined. This consensus was initiated to provide insight into those situations where a LTBA might be considered the Standard of Care in ventral hernia repair grades 2-3 (original classification, 2010) of the Ventral Hernia Working Group. METHODS: A steering group of expert surgeons identified 35 statements, based around the evidence supporting LTBA, surgical technique, patients type most suitable for LTBA, risk-benefit of LTBA, patient and surgeon considerations, LTBA value. Surgeons involved in hernia repair received an online survey to assess consensus with these statements. Consensus was defined as high if ≥ 70% and very high if ≥ 90% of respondents agreed. Statements that had not achieved consensus agreement were revised and these were then issued for a subsequent round. Finally, 34 statements were included. RESULTS: Two hundred fifty-five surgeons were involved. Fourteen statements (41%) achieved very high consensus, 24 achieved consensuses (≥ 70-< 90%), whilst one (3%) just failed to achieve consensus with an agreement score of 69%. CONCLUSIONS: Expert consensus opinion about the use of LTBA for hernia (Grades 2-3) as the Standard of Care was achieved. Based on the consensus scores, the steering group derived eleven keys.

Slowly absorbable mesh versus standard care in the management of contaminated midline incisional hernia (COMpACT-BIO): a multicentre randomised controlled phase III trial including a health economic evaluation.

INTRODUCTION: Incisional hernia (IH) is the most frequent mid-term and long-term complication after midline laparotomy. The current standard treatment includes repair using a mesh. In a contaminated field, the use of a non-absorbable mesh increases the risk of surgical site infection and the costs. Slowly absorbable meshes are safe in contaminated fields, but no data have been reported regarding their long-term recurrence rate. COMpACT-BIO is a multicentre prospective randomised controlled phase III trial designed to compare the 3-year recurrence rate in patients undergoing contaminated IH repair with either a slowly absorbable mesh or standard care. METHODS: In patients undergoing midline IH repair in a contaminated surgical field (grade III of the modified Ventral Hernia Working Group classification), the COMpACT-BIO study compares the use of a slowly absorbable mesh with that of conventional care according to standardised surgical procedures (primary closure, non-absorbable synthetic mesh or biologic mesh, at the discretion of the surgeon). Randomisation is done during surgery before closure the fascia with an allocation ratio of 1:1. The choice of the slowly absorbable mesh is left to the criteria of each centre. The primary endpoint is the proportion of patients with scan-confirmed IH recurrence within 3 years after repair. ETHICS/DISSEMINATION: This trial is conducted in compliance with international standards for research practice and reporting. Written informed consent will be obtained from patients prior to inclusion. All data were identified and anonymised prior to analysis. The protocol has been approved by an Institutional Review Board (2020-A0823-36/SI:20.07.03.66831), and will be conducted in compliance with the CONSORT (Consolidated Standards of Reporting Trials) statement. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals. PROTOCOL VERSION: Version 2-13 October 2020. TRIAL REGISTRATION NUMBER: NCT04597840.

Benefit of a flash dose of corticosteroids in digestive surgical oncology: a multicenter, randomized, double blind, placebo-controlled trial (CORTIFRENCH).

BACKGROUND: The modulation of perioperative inflammation seems crucial to improve postoperative morbidity and cancer-related outcomes in patients undergoing oncological surgery. Data from the literature suggest that perioperative corticosteroids decrease inflammatory markers and might be associated with fewer complications in esophageal, liver, pancreatic and colorectal surgery. Their benefit on cancer-related outcomes has not been assessed. METHODS: The CORTIFRENCH trial is a phase III multicenter randomized double-blind placebo-controlled trial to assess the impact of a flash dose of preoperative corticosteroids versus placebo on postoperative morbidity and cancer-related outcomes after elective curative-intent surgery for digestive cancer. The primary endpoint is the frequency of patients with postoperative major complications occurring within 30 days after surgery (defined as all complications with Clavien-Dindo grade > 2). The secondary endpoints are the overall survival at 3 years, the disease-free survival at 3 years, the frequency of patients with intraabdominal infections and postoperative infections within 30 days after surgery and the hospital length of stay. We hypothesize a reduced risk of major complications and a better disease-survival at 3 years in the experimental group. Allowing for 5% of drop-out, 1 200 patients (600 per arm) should be included. DISCUSSION: This will be the first trial focusing on the impact of perioperative corticosteroids on cancer related outcomes. If significant, it might be a strong improvement on oncological outcomes for patients undergoing surgery for digestive cancers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03875690, Registered on March 15, 2019, URL: https://clinicaltrials.gov/ct2/show/NCT03875690 .

Ano-rectovaginal fistula after obstetrical anal sphincter injury: Diverting stoma does not improve the surgical results.

AIM: Ano-rectovaginal fistulas (ARVF) are challenging for the surgeon. Most of the series mix aetiologies, leading to confusion with respect to the conclusion. The aim of this study was to assess the factors associated with the success of ARVF management following obstetrical anal sphincter injury (OASIS). METHODS: This retrospective multicentric study included all the patients undergoing surgery for ARVF identified by the hospital codes. Patients for whom the aetiology of ARVF was not OASIS were excluded. The major outcome measure was the success of the procedure. RESULTS: Sixty patients with treated ARVF due to OASIS were identified. The success of overall management was 91.7%. Female patients underwent a mean of 2.5 (±1.7) procedures. A diverting stoma was formed in 29 patients (48.3%) of which 26 were closed at the end of the management period (89.7%). Of the 148 surgical procedures, only 55 were successful (37.2%). The order of the procedures (OR = 1.38; 95% CI: 0.75-2.51) or the diverting stoma (OR = 1.46; 95% CI: 0.31-6.91) were not significantly associated with the success of the surgery. However, Martius flap (OR = 4.13; 95% CI: 1.1-15.54) and Musset procedures (OR = 5.79; 95% CI: 1.77-18.87) produced better results than the endorectal advancement flap (ERAF). The other procedures did not show a significant correlation with management success. CONCLUSION: A diverting stoma is not mandatory in the management of ARVF due to OASIS to improve the success of the surgical procedure. While the Martius flap procedure offers better results, the ERAF procedure may be preferred as a primary intervention in the absence of sphincter injury as it is less invasive. In cases of residual sphincter injury, the Musset procedure is most likely to be the best option.

Lipidomic profiling of exosomes from colorectal cancer cells and patients reveals potential biomarkers.

Strong evidence suggests that differences in the molecular composition of lipids in exosomes depend on the cell type and has an influence on cancer initiation and progression. Here, we analyzed by liquid chromatography-mass spectrometry (LC-MS) the lipidomic signature of exosomes derived from the human cell lines normal colon mucosa (NCM460D), and colorectal cancer (CRC) nonmetastatic (HCT116) and metastatic (SW620), and exosomes isolated from the plasma of nonmetastatic and metastatic CRC patients and healthy donors. Analysis of this exhaustive lipid study highlighted changes in some molecular species that were found in the cell lines and confirmed in the patients. For example, exosomes from primary cancer patients and nonmetastatic cells compared with healthy donors and control cells displayed a common marked increase in phosphatidylcholine (PC) 34 : 1, phosphatidylethanolamine (PE) 36 : 2, sphingomyelin (SM) d18 : 1/16 : 0, hexosylceramide (HexCer) d18 : 1/24 : 0 and HexCer d18 : 1/24 : 1. Interestingly, these same lipids species were decreased in the metastatic cell line and patients. Further, levels of PE 34 : 2, PE 36 : 2, and phosphorylated PE p16 : 0/20 : 4 were also significantly decreased in metastatic conditions when compared to the nonmetastatic counterparts. The only molecule species found markedly increased in metastatic conditions (in both patients and cells) when compared to controls was ceramide (Cer) d18 : 1/24 : 1. These decreases in lipid species in the extracellular vesicles might reflect function-associated changes in the metastatic cell membrane. Although these potential biomarkers need to be validated in a larger cohort, they provide new insight toward the use of clusters of lipid biomarkers rather than a single molecule for the diagnosis of different stages of CRC.

Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human.

White adipose tissue (WAT) possesses the endocannabinoid system (ECS) machinery and produces the two major endocannabinoids (ECs), arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). Accumulating evidence indicates that WAT cannabinoid 1 receptors (CB1R) are involved in the regulation of fat storage, tissue remodeling and secretory functions but their role in controlling lipid mobilization is unclear. In the present study, we used different strategies to acutely increase ECS activity in WAT and tested the consequences on glycerol production as a marker of lipolysis. Treating lean mice or rat WAT explants with JLZ195, which inhibits ECs degrading enzymes, induced an increase in 2-AG tissue contents that was associated with a CB1R-dependent decrease in lipolysis. Direct treatment of rat WAT explants with AEA also inhibited glycerol production while mechanistic studies revealed it could result from the stimulation of Akt-signaling pathway. Interestingly, AEA treatment decreased lipolysis both in visceral and subcutaneous WAT collected on lean subjects suggesting that ECS also reduces fat store mobilization in Human. In obese mice, WAT content and secretion rate of ECs were higher than in control while glycerol production was reduced suggesting that over-produced ECs may inhibit lipolysis activating local CB1R. Strikingly, our data also reveal that acute CB1R blockade with Rimonabant did not modify lipolysis in vitro in obese mice and human explants nor in vivo in obese mice. Taken together, these data provide physiological evidence that activation of ECS in WAT, by limiting fat mobilization, may participate in the progressive tissue remodeling that could finally lead to organ dysfunction. The present findings also indicate that acute CB1R blockade is inefficient in regulating lipolysis in obese WAT and raise the possibility of an alteration of CB1R signaling in conditions of obesity.

Lactobacillus stress protein GroEL prevents colonic inflammation.

BACKGROUND: We previously showed that supernatants of Lactobacillus biofilms induced an anti-inflammatory response by affecting the secretion of macrophage-derived cytokines, which was abrogated upon immunodepletion of the stress protein GroEL. METHODS: We purified GroEL from L. reuteri and analysed its anti-inflammatory properties in vitro in human macrophages isolated from buffy coats, ex vivo in explants from human biopsies and in vivo in a mouse model of DSS induced intestinal inflammation. As a control, we used GroEL purified (LPS-free) from E. coli. RESULTS: We found that L. reuteri GroEL (but not E. coli GroEL) inhibited pro-inflammatory M1-like macrophages markers, and favored M2-like markers. Consequently, L. reuteri GroEL inhibited pro-inflammatory cytokines (TNFα, IL-1ß, IFNγ) while favouring an anti-inflammatory secretome. In colon tissues from human biopsies, L. reuteri GroEL was also able to decrease markers of inflammation and apoptosis (caspase 3) induced by LPS. In mice, we found that rectal administration of L. reuteri GroEL (but not E. coli GroEL) inhibited all signs of haemorrhagic colitis induced by DSS including intestinal mucosa degradation, rectal bleeding and weight loss. It also decreased intestinal production of inflammatory cytokines (such as IFNγ) while increasing anti-inflammatory IL-10 and IL-13. These effects were suppressed when animals were immunodepleted in macrophages. From a mechanistic point of view, the effect of L. reuteri GroEL seemed to involve TLR4, since it was lost in TRL4-/- mice, and the activation of a non-canonical TLR4 pathway. CONCLUSIONS: L. reuteri GroEL, by affecting macrophage inflammatory features, deserves to be explored as an alternative to probiotics.

Simultaneous Versus Delayed Resection for Initially Resectable Synchronous Colorectal Cancer Liver Metastases: A Prospective, Open-label, Randomized, Controlled Trial.

OBJECTIVE: To answer whether synchronous colorectal cancer liver metastases (SLM) should be resected simultaneously with primary cancer or should be delayed. SUMMARY BACKGROUND DATA: Numerous studies have compared both strategies. All were retrospective and conclusions were contradictory. METHODS: Adults with colorectal cancer and resectable SLM were randomly assigned to either simultaneous or delayed resection of the metastases. The primary outcome was the rate of major complications within 60 days following surgery. Secondary outcomes included overall and disease-free survival. RESULTS: A total of 105 patients were recruited. Eighty-five patients (39 and 46 in the simultaneous- and delayed-resection groups, respectively) were analyzed. The percentage of major perioperative complications did not differ between groups (49% and 46% in the simultaneous- and delayed-resection groups, respectively, adjusted OR 0.84, 95% CI 0.35-2.01; P = 0.70, logistic regression). Complications rates were 28% and 13% (P = 0.08, χ2 test) at colorectal site and 15% and 17% (P = 0.80, χ2 test) at liver site, in simultaneous- and delayed-resection groups, respectively. In the delayed-resection group, 8 patients did not reach the liver resection stage, and this was due to disease progression in 6 cases. After 2 years, overall and disease-free survival tended to be improved in simultaneous as compared with delayed-resection groups (P = 0.05), a tendency which persisted for OS after a median follow-up of 47 months. CONCLUSIONS: Complication rates did not appear to differ when colorectal cancer and synchronous liver metastases are resected simultaneously. Delayed resection tended to impair overall survival.

Is Lanreotide Really Useful in High Output Stoma? Comparison between Lanreotide to Conventional Antidiarrheal Treatment Alone.

BACKGROUND: The incidence of high-output stoma (HOS) was reported to be approximately 3 to 16% in the literature, and HOS can cause dehydration. This complication is often severe enough to warrant hospital readmission and may result in renal failure. The aim of this study was to show a decrease of 50% in ileostomy output in the experimental arm using lanreotide treatment. METHODS: Patients with an ileostomy output ≥ 1.5 l/24 hours were included in this prospective, open, multicentre randomized trial. Patients were randomly allocated between treatment arms with either lanreotide (LAN) and antidiarrhoeal treatments (TAD) (LAN-TAD group) or antidiarrhoeal treatments only (TADS group). The primary outcome was ileostomy output after 72 days. The secondary endpoints were ileostomy output during the first 6 days, blood urea and creatinine values, hospital length of stay and serious adverse events. RESULTS: In the per-protocol analysis, there were nine patients in the control group (TADS) and six patients in the experimental group (TAD-LAN group). The stoma outputs at Day 3 (D3) in the experimental and control groups were 1,900 ± 855.7 mL and 1,728.6 ± 845.5 mL, respectively (p = 0.2). No differences were found concerning stoma output at D6, renal function, or hospital length of stay between the two groups. CONCLUSION: The trial was prematurely stopped due to the low number of patients included. The question of the usefulness of somatostatin analogues in HOS persists, especially as the cost of this treatment is high, and there is a lack of evidence of its effectiveness.

Enteral versus parenteral nutrition in the conservative treatment of upper gastrointestinal fistula after surgery: a multicenter, randomized, parallel-group, open-label, phase III study (NUTRILEAK study).

BACKGROUND: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. METHODS/DESIGN: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. DISCUSSION: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.

Recurrence after elective incisional hernia repair is more frequent than you think: An international prospective cohort from the French Society of Surgery.

BACKGROUND: The French Society of Surgery has endorsed a cohort aiming to prospectively assess the frequency of recurrence after incisional hernia repair and to identify the risk factors. METHODS: Consecutive patients undergoing incisional hernia repair in the participating centers were included in the prospective French Society of Surgery cohort over a 6-month period. Patients were followed up with a computed tomography scan at 1 y and a clinical assessment by the surgeon at 2 years. RESULTS: A total of 1,075 patients undergoing incisional hernia repair were included in 61 participating centers. The median follow-up was 24.0 months (interquartile range: 14.0-25.3). The follow-up rates were 83.0% and 68.5% at 1 and 2 years, respectively. The recurrence rates were 18.1% at 1 year and 27.7% at 2 years. Recurrence risk factors at 2 years were a history of hernia (odds ratio = 1.57, 95% confidence interval = 1.05-2.35, P = .028), a lateral hernia (odds ratio = 1.84, 95% confidence interval = 1.19-2.86, P = .007), a concomitant digestive operation (odds ratio = 1.97, 95% confidence interval = 1.20-3.22, P = .007), and the occurrence of early surgical site complications (odds ratio = 1,90, 95% confidence interval = 1.06-3.38, P = .030). The use of surgical mesh was strongly associated with a lower risk of recurrence at 2 years (P < .001). CONCLUSION: After incisional hernia repair, the 2-year recurrence rate is as high as 27.7%. History of hernia, lateral hernia, concomitant digestive operation, the onset of surgical site complications, and the absence of mesh are strong risk factors for recurrence.

CHIPOFIL: A pilot study assessing the feasibility of HIPEC without extracorporeal circuit.

BACKGROUND: Heated intraperitoneal chemotherapy (HIPEC) is currently performed using an external circuit including a heating device and a pump. Available devices have several drawbacks in terms of costs, technique (flow surges due to blocked tubes) and staff safety, hindering a wider use. In a previous preclinical study conducted in animals, we placed a heating wire within the abdomen to achieve and maintain hyperthermia. Our results showed this technique is safe and effective. The present pilot study was conceived as the first use of such a device in humans, aiming to confirm its safety and efficacy. METHODS: This was a pilot study designed to include 13 patients undergoing HIPEC. Two sets of the prototype were placed within the abdominal cavity, one in the supramesocolic and one in the inframesocolic space. The target temperature was 42-43 °C during 30-90 min according to the protocol defined for each patient. The time to set up, heat and dismantle was measured. All complications were recorded during the first postoperative year and evaluated by an independent committee. RESULTS: Nine women and four men were included. The median time to set on the device was 25 min. The target temperature was obtained in a median of 14 min and maintained uniform and homogeneously distributed within the abdomen for the scheduled duration. A permanent stirring of the viscera was performed. No thermal injury or device-related complications were observed. There were two anastomotic leaks (only one requiring reoperation), two hemoperitoneum requiring reoperation, one evisceration and one gastroparesia. CONCLUSIONS: A heating cable within the peritoneal cavity can achieve safe, simple, fast and efficient HIPEC.