Enucleation for sporadic non-functioning pancreatic neuroendocrine tumors larger than 2 centimeters is associated with equivalent morbidity and survival compared to smaller tumors: a multi-institutional study.

INTRODUCTION: Non-functioning pancreatic neuroendocrine tumor (NF-PanNET) ≤ 2 cm can be observed or resected. Surgery remains recommended for NF-PanNET > 2 cm but its extent, enucleation (EN) versus formal resection, remains controversial. METHODS: Multicentric retrospective cohort of sporadic NF-PanNET patients treated with EN. Short and long-term outcomes were compared according to tumor size on imaging ≤ 2 cm vs > 2 cm. RESULTS: 131patients underwent EN for NF-PanNET, including 103 (79.0%) ≤ 2 cm and 28 (21.0%) > 2 cm (extremes, 4-55 mm). Patients' characteristics were comparable, and tumor characteristics only differed in their diameter. Clavien III-IV complications were similar (18.4% vs 17.9%, p= 1.00) with one death in NF-PanNET ≤ 2cm. Grade B/C pancreatic fistula were comparable (16.5% vs 10.7%, p= 0.850). In NF-PanNET > 2cm there were more pT2/3 stage tumors (85.7% vs 21.4%, p<0.001), similar rates of grade G2/3 tumors (25% vs 16.5%, p= 0.408) with a median Ki67 of 2 (IQR: 1-3), and of lymphovascular and perineural invasions. Lymph node picking was done in 46 (35.1%) patients, with a higher median number of harvested lymph nodes in NF-PanNET > 2 cm (4 vs 3, p= 0.01). All were pN0. R0 resection rate (78.6% vs 82.5%, respectively; p= 0.670) was equivalent. Five-year overall (100% vs 99%, p= 0.602) and 10-year disease-free (96% vs 92%, respectively; p= 0.532) survivals were comparable. CONCLUSIONS: EN for selected NF-PanNET > 2 cm carries equivalent morbidity, overall and disease-free survivals compared to those observed with NF-PanNET ≤ 2 cm.

Step-up approach for the treatment of infected necrotising pancreatitis: real life data from a single-centre experience with long-term follow-up.

BACKGROUND: About 20% of patients with acute pancreatitis develop a necrotising form with a worse prognosis due to frequent appearance of organ failure(s) and/or infection of necrosis. Aims of the present study was to evaluate the "step up" approach treatment of infected necrosis in terms of: feasibility, success in resolving infection, morbidity of procedures, risk factors associated with death and long-term sequels. METHODS: In this observational retrospective monocentric study in the real life, necrotizing acute pancreatitis at the stage of infected walled-off necrosis were treated as follow: first step with drainage (radiologic and/or endoscopic-ultrasound-guided with lumen apposing metal stent); in case of failure, minimally invasive necrosectomy sessions(s) by endoscopy through the stent and/or via retroperitoneal surgery (step 2); If necessary open surgery as a third step. Efficacy was assessed upon to a composite clinical-biological criterion: resolution of organ failure(s), decrease of at least two of clinico-biological criteria among fever, CRP serum level, and leucocytes count). RESULTS: Forty-one consecutive patients were treated. The step-up strategy: (i) was feasible in 100% of cases; (ii) allowed the infection to be resolved in 33 patients (80.5%); (iii) Morbidity was mild and rapidly resolutive; (iv) the mortality rate at 6 months was of 19.5% (significant factors: SIRS and one or more organ failure(s) at admission, fungal infection, size of the largest collection ≥ 16 cm). During the follow-up (median 72 months): 27% of patients developed an exocrine pancreatic insufficiency, 45% developed or worsened a previous diabetes, 24% had pancreatic fistula and one parietal hernia. CONCLUSIONS: Beside a very good feasibility, the step-up approach for treatment of infected necrotizing pancreatitis in the real life displays a clinico-biological efficacy in 80% of cases with acceptable morbidity, mortality and long-term sequels regarding the severity of the disease.

Curative surgical treatment of common bile duct stones: Retrospective cohort study.

BACKGROUND: In the event of symptomatic common bile duct (CBD) stones with dilated CBD, one possible curative treatment option is stone extraction through choledocotomy associated with cholecystectomy. Endoscopic treatment is only reserved for residual stones at 6 weeks. The aim of this study was to evaluate the results from laparoscopic curative surgical treatment of CBD stones with dilated CBD. METHODS: This is a retrospective single-centered cohort study. All consecutive patients admitted for laparoscopic cholecystectomy with evidence of CBD stones with dilated CBD from January 2010 to December 2020 at our center were included. Success was defined by CBD clearance at 6 weeks. Need for additional procedures, such as endoscopic sphincterotomy, immediate, and end-of-procedure morbi-mortality as well as factors associated with procedure failure, were also studied. RESULTS: A total of 246 patients who received curative treatment were included in the study. The success rate for the curative treatment was 93.1% (229 patients). Immediate postoperative morbidity was 24.4% with a 5.3% reintervention rate. Immediate and 6-week postoperative mortality rates were zero and 0.4%, respectively. The mean length of stay was 11.3 days. Factors associated with procedure failure appeared to be the occurrence of an early postoperative complication and the need for readmission during the period between surgery and drain removal. CONCLUSION: This study indicates that laparoscopic curative surgical treatment for symptomatic CBD stones may be performed with acceptable results without routine need for additional procedures.

Postoperative ileus after digestive surgery: Network meta-analysis of pharmacological intervention.

AIMS: Several medicinal treatments for avoiding postoperative ileus (POI) after abdominal surgery have been evaluated in randomized controlled trials (RCTs). This network meta-analysis aimed to explore the relative effectiveness of these different treatments on ileus outcome measures. METHODS: A systematic literature review was performed to identify RCTs comparing treatments for POI following abdominal surgery. A Bayesian network meta-analysis was performed. Direct and indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analysis. RESULTS: A total of 38 RCTs were included in this network meta-analysis reporting on 6371 patients. Our network meta-analysis shows that prokinetics significantly reduce the duration of first gas (mean difference [MD] = 16 h; credible interval -30, -3.1; surface under the cumulative ranking curve [SUCRA] 0.418), duration of first bowel movements (MD = 25 h; credible interval -39, -11; SUCRA 0.25) and duration of postoperative hospitalization (MD -1.9 h; credible interval -3.8, -0.040; SUCRA 0.34). Opioid antagonists are the only treatment that significantly improve the duration of food recovery (MD -19 h; credible interval -26, -14; SUCRA 0.163). CONCLUSION: Based on our meta-analysis, the 2 most consistent pharmacological treatments able to effectively reduce POI after abdominal surgery are prokinetics and opioid antagonists. The absence of clear superiority of 1 treatment over another highlights the limits of the pharmacological principles available.

Survival analysis and prognostic factors of retroperitoneal liposarcoma curative surgery in a single centre. Analysis of adjacent organ invasion between imaging and definitive histopathology.

INTRODUCTION: Retroperitoneal liposarcoma (RPL) is a rare primary mesenchymal tumour that develops in retroperitoneal adipose tissue. Unlike the majority of published series, this homogeneous cohort focuses on RPL. The main purpose of this study is to evaluate the overall and recurrence-free survival of RPLs who underwent excision surgery and the prognostic factors involved. PATIENTS AND METHODS: A total of 82 patients from a single centre, who underwent curative surgery for histologically confirmed retroperitoneal liposarcoma between 2008 and 2020, were analysed in the study. Compartmental surgical excision was advised as per the guidelines. The primary endpoints were 5 years of overall survival and recurrence-free survival. Predictable tumour invasion of adjacent organs, based on a pre-operative CT scan, was also investigated to test the correlation between pre-operative imaging and pathological data. RESULTS: Median follow-up was 61.6 months. Five year overall survival was 71.9% [95% CI: 59.8; 80.9] and 5 year recurrence-free survival was 49% [95% CI: 36.4; 60.5]. Following multivariable analysis, the factors influencing overall survival were tumour rupture and onset of severe complications (Dindo-Clavien grade ≥3). Factors influencing recurrence-free survival were neoadjuvant radiotherapy and tumour rupture. A significant correlation (p < 0.05) was found between predicted invasion based on a CT scan of the colon, spleen, adrenal gland, posterior abdominal wall and diaphragm, and pathological invasion. CONCLUSIONS: Curative compartmental surgery remains the gold standard treatment for RPL. This study, highlights the fact that the quality of the surgical excision is a crucial factor in patient prognosis.

Boot camp approach to surgical residency preparation: feedback from a French university hospital.

INTRODUCTION: The transition from medical student to surgical resident is not a simple one. The aim of this study was to report the experience of a university hospital in the organization of the induction course for future surgical residents and the contribution of a video support in the learning of the suture. MATERIAL AND METHOD: We were able to study two consecutive years of students (October 2020 and 2021). Concerning the practical and technical workshops (learning suture) we carried out a comparative study between two groups of students. A group that had video support for learning suture (video group) and a group without video (control group). The evaluation of the suture was performed in a blinded manner by two supervising surgeons. The other practical workshop was drain fixation; the students did not have a video for this workshop. A comparative study was also performed for the drain fixation workshop between the two groups (video group and control group). A program of theoretical courses was also set up. This program is established according to the different future functions of the residents by integrating medico-legal notions and teamwork. Satisfaction questionnaires were given to the students and the answers were given two months after taking up their duties in the hospital (6 questions with Likert scale and 4 free questions). RESULTS: The cohort consisted of 58 students (29 each in 2020 and 29 in 2021). Comparative analyses of the evaluation of the suture workshops showed better performance in the video group compared with the group without video. The comparison of these two groups did not show significant differences in the drain fixation workshop. The theoretical teaching was broken down according to the students' future tasks and each speaker was a specialist in his or her field of expertise. The results of the questionnaires showed a desire on the part of the students to increase the time spent on practical workshops and theoretical forensic teaching. CONCLUSION: We were able to show through these two years of a program that we were able to offer a surgical resident preparation course. In addition, we have highlighted the contribution of a video support in the learning curve of the suture.

Life expectancy and likelihood of surgery in multiple endocrine neoplasia type 1: AFCE and GTE cohort study.

BACKGROUND: The overall natural history, risk of death and surgical burden of patients with multiple endocrine neoplasia type 1 (MEN1) is not well known. METHODS: Patients with MEN1 from a nationwide cohort were included. The survival of patients with MEN1 was compared with that of the general population using simulated controls. The cumulative probabilities of MEN1-specific operations and postoperative mortality were assessed, and surgical sequences were analysed using sunburst charts and Venn diagrams. RESULTS: A total of 1386 patients with MEN1 were included. Life expectancy was significantly reduced in patients with MEN1 compared with simulated controls from the general population, with a lifetime difference of 15 years. Mutations affecting the JunD interaction domain had a significant negative impact on survival. Survival for patients with MEN1 compared with the general population improved over time. The probability of experiencing at least one specific MEN1 operation was above 95 per cent after 75 years, and most patients had surgery at least twice during their lifetime. Time to a 50 per cent risk of MEN1 surgery was 30.5 years for patients born after 1960, compared with 47.9 years for those born before 1960. Sex and mutations affecting the JunD interacting domain had no impact on time to first surgery. There was considerable heterogeneity in surgical sequences, with no specific clinical pathway. CONCLUSION: Life expectancy was significantly lower among patients with MEN1 compared with the general population, and further decreased in patients with mutations affecting the JunD interacting domain. Almost all patients underwent at least one MEN1-specific operation during their lifetime, but there was no standardized sequence of surgery.

Oncologic and Functional Outcomes of Pelvic Perineal Reconstruction by Perineal Colostomy and Malone Procedure After Abdominoperineal Resection.

BACKGROUND: Abdominoperineal resection is the standard curative surgical technique for locally advanced adenocarcinoma of the lower rectum and squamous cell carcinoma of the anal canal after chemoradiotherapy. However, it requires a definitive abdominal colostomy that modifies the body appearance. OBJECTIVE: The study aim was to evaluate the combination of abdominoperineal resection with perineal colostomy reconstruction and Malone antegrade continence enema. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at the Toulouse Hospital Digestive Surgery Department. PATIENTS: All of the patients with advanced adenocarcinoma or squamous cell carcinoma who underwent abdominoperineal resection with perineal colostomy reconstruction and Malone antegrade continence enema (n = 80) between December 1999 and December 2016 were included. MAIN OUTCOME MEASURES: The main outcome was the 5-year overall survival rate. RESULTS: The 5-year overall survival was 74.89% (95% CI, 62.91%-83.50%), and the median recurrence-free survival was 107.6 months (95% CI, 65.1-198.1 mo). The median follow-up was 91.0 months (95% CI, 70.4-116.6 mo). R0 resection was obtained in 64 patients (80.0%). The median Cleveland Clinic Incontinence Score (to assess the functional outcomes) was 9.0 (interquartile range, 1.0-18.0), and it was lower in patients with advanced adenocarcinoma than with squamous cell carcinoma (7.0 (interquartile range, 2.0-18.0) vs 11.0 (interquartile range, 1.0-17.0); p = 0.01). Eleven patients (13.8%) reported perineal stains during the night, and 19 patients (23.8%) needed drugs to reduce colon motility. The rate of severe complications (Clavien-Dindo >II) was 11.7% (n = 9). Definitive colostomy was performed in 15 patients (18.8%). LIMITATIONS: This retrospective study included a small number of patients from a single center. Moreover, the functional outcome was tested with self-report questionnaires (risk of response bias). CONCLUSIONS: This study suggests that abdominoperineal resection associated with perineal reconstruction by perineal colostomy and Malone antegrade continence enema is safe and may improve patient quality of life. See Video Abstract at http://links.lww.com/DCR/B629. RESULTADOS ONCOLGICOS Y FUNCIONALES DE LA RECONSTRUCCIN PLVIPERINEAL MEDIANTE COLOSTOMA PERINEAL Y PROCEDIMIENTO DE MALONE DESPUS DE LA RESECCIN ABDOMINOPERINEAL: ANTECEDENTES:La resección abdominoperineal es la técnica quirúrgica curativa estándar para el tratamiento del adenocarcinoma localmente avanzado del recto inferior y el carcinoma a células escamosas del canal anal, después de radio-quimioterapia. Sin embargo, requiere una colostomía abdominal definitiva que modifica la apariencia corporal.OBJETIVO:El propósito del presente estudio fue el evaluar la combinación de la resección abdominoperineal con la confección de una colostomía perineal asociada a enemas de continencia anterógrada según Malone.DISEÑO:Estudio retrospectivo.AJUSTES:Servicio de Cirugía Digestiva del Hospital de Toulouse, Francia.PACIENTES:Se incluyeron todos los pacientes con adenocarcinoma avanzado o carcinoma de células escamosas que se sometieron a resección abdominoperineal con la confección de una colostomía perineal asociada a enemas de continencia anterógrada según Malone (n = 80) entre diciembre de 1999 y diciembre de 2016.PRINCIPALES MEDIDAS DE RESULTADO:El principal resultado fue la tasa de sobrevida global a 5 años.RESULTADOS:La sobrevida global a 5 años fue de 74,89% (IC del 95%, 62,91 a 83,50) y la mediana de supervivencia libre de recurrencia fue de 107,6 meses (IC del 95%, 65,1 a 198,1). La mediana de seguimiento fue de 91,0 meses (IC del 95%, 70,4-116,6). La resección R0 se obtuvo en 64 pacientes (80,0%). La mediana de puntuación de la escala de incontinencia de la Cleveland Clinic (para evaluar los resultados funcionales) fue de 9,0 [1,0; 18,0], y fue menor en pacientes con adenocarcinoma avanzado que con carcinoma de células escamosas (7,0 [2,0; 18,0] versus 11,0 [1,0; 17,0]; p = 0,01). Once pacientes (13,8%) refirieron manchado perineal nocurno y 19 pacientes (23,8%) necesitaron fármacos para reducir la motilidad del colon. La tasa de complicaciones graves (Clavien-Dindo > II) fue del 11,7% (n = 9). Se realizó colostomía definitiva en 15 (18,8%) pacientes.LIMITACIONES:Este estudio retrospectivo incluyó un pequeño número de pacientes y de un solo centro. Además, el resultado funcional se probó con cuestionarios de autoinforme (riesgo de sesgo de respuesta).CONCLUSIONES:Este estudio sugiere que la resección abdominoperineal asociada con la confección de una colostomía perineal asociada a enemas de continencia anterógrada según Malone es segura y puede mejorar la calidad de vida de los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B629.

Splenic volume and splenic vein diameter are independent pre-operative risk factors of portal vein thrombosis after splenectomy: a retrospective cohort study.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication following splenectomy. It affects between 5 and 55% of patients undergoing surgery with no clearly defined pre-operative risk factors. The aim of this study was to determine the pre-operative risk factors of PVT. PATIENTS AND METHOD: Single centre, retrospective study of data compiled for every consecutive patient who underwent splenectomy at Toulouse University Hospital between January 2009 and January 2019. Patients with pre- and post-surgical CT scans have been included. RESULTS: 149 out of 261 patients were enrolled in the study (59% were males, mean age 52 years). The indications for splenectomy were splenic trauma (30.9%), malignant haemopathy (26.8%) and immune thrombocytopenia (8.0%). Twenty-nine cases of PVT (19.5%) were diagnosed based on a post-operative CT scan performed on post-operative day (POD) 5. Univariate analysis identifies three main risk factors associated with post-operative PVT: estimated splenic weight exceeding 500 g with an OR of 8.72 95% CI (3.3-22.9), splenic vein diameter over 10 mm with an OR of 4.92 95% CI (2.1-11.8) and lymphoma with an OR of 7.39 (2.7-20.1). The role of splenic vein diameter with an OR of 3.03 95% CI (1.1-8.6), and splenic weight with an OR of 5.22 (1.8-15.2), as independent risk factors is confirmed by multivariate analysis. A screening test based on a POD 5 CT scan with one or two of these items present could indicate sensitivity of 86.2% and specificity of 86.7%. CONCLUSION: This study suggests that pre-operative CT scan findings could predict post-operative PVT. A CT scan should be performed on POD 5 if a risk factor has been identified prior to surgery.

Updated Trends in Imaging Practices for Pancreatic Neuroendocrine Tumors (PNETs): A Systematic Review and Meta-Analysis to Pave the Way for Standardization in the New Era of Big Data and Artificial Intelligence.

PURPOSE: Medical imaging plays a central and decisive role in guiding the management of patients with pancreatic neuroendocrine tumors (PNETs). Our aim was to synthesize all recent literature of PNETs, enabling a comparison of all imaging practices. METHODS: based on a systematic review and meta-analysis approach, we collected; using MEDLINE, EMBASE, and Cochrane Library databases; all recent imaging-based studies, published from December 2014 to December 2019. Study quality assessment was performed by QUADAS-2 and MINORS tools. RESULTS: 161 studies consisting of 19852 patients were included. There were 63 'imaging' studies evaluating the accuracy of medical imaging, and 98 'clinical' studies using medical imaging as a tool for response assessment. A wide heterogeneity of practices was demonstrated: imaging modalities were: CT (57.1%, n=92), MR (42.9%, n=69), PET/CT (13.3%, n=31), and SPECT/CT (9.3%, n=15). International imaging guidelines were mentioned in 2.5% (n=4/161) of studies. In clinical studies, imaging protocol was not mentioned in 30.6% (n=30/98) of cases and only mentioned imaging modality without further information in 63.3% (n=62/98), as compared to imaging studies (1.6% (n=1/63) of (p<0.001)). QUADAS-2 and MINORS tools deciphered existing biases in the current literature. CONCLUSION: We provide an overview of the updated current trends in use of medical imaging for diagnosis and response assessment in PNETs. The most commonly used imaging modalities are anatomical (CT and MRI), followed by PET/CT and SPECT/CT. Therefore, standardization and homogenization of PNETs imaging practices is needed to aggregate data and leverage a big data approach for Artificial Intelligence purposes.

Randomised clinical trial for the cost-utility evaluation of two strategies of perineal reconstruction after abdominoperineal resection in the context of anorectal carcinoma: biological mesh repair versus primary perineal wound closure, study protocol for the GRECCAR 9 Study.

INTRODUCTION: Abdominoperineal resections performed for anorectal tumours leave a large pelvic and perineal defect causing a high rate of morbidity of the perineal wound (40%-60%). Biological meshes offer possibilities for new standards of perineal wound reconstruction. Perineal fillings with biological mesh are expected to increase quality of life by reducing perineal morbidity. METHODS AND ANALYSIS: This is a multicentre, randomised and single-blinded study with a blinded endpoint evaluation, the experimental arm of which uses a biological mesh and the control arm of which is defined by the primary closure after abdominoperineal resection for cancer. Patients eligible for inclusion are patients with a proven history of rectal adenocarcinoma and anal canal epidermoid carcinoma for whom abdominoperineal resection was indicated after a multidisciplinary team discussion. All patients must have social security insurance or equivalent social protection. The main objective is to assess the incremental cost-utility ratio (ICUR) of two strategies of perineal closure after an abdominoperineal resection performed for anorectal cancer treatment: perineal filling with biological mesh versus primary perineal closure (70 patient in each arm). The secondary objectives focus on quality of life and morbidity data during a 1-year follow-up. Deterministic and probabilistic sensitivity analyses will be performed in order to estimate the uncertainty surrounding the ICUR. CIs will be constructed using the non-parametric bootstrap approach. A cost-effectiveness acceptability curve will be built so as to estimate the probability of efficiency of the biological meshes given a collective willingness-to-pay threshold. ETHICS AND DISSEMINATION: The study was approved by the Regional Ethical Review Board of 'Nord Ouest 1' (protocol reference number: 20.05.14.60714; national number: 2020-A01169-30).The results will be disseminated through conventional scientific channels. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02841293).

Five-Year Survival Outcomes of Hybrid Minimally Invasive Esophagectomy in Esophageal Cancer: Results of the MIRO Randomized Clinical Trial.

Importance: Available data comparing the long-term results of hybrid minimally invasive esophagectomy (HMIE) with that of open esophagectomy are conflicting, with similar or even better results reported for the minimally invasive esophagectomy group. Objective: To evaluate the long-term, 5-year outcomes of HMIE vs open esophagectomy, including overall survival (OS), disease-free survival (DFS), and pattern of disease recurrence, and the potential risk factors associated with these outcomes. Design, Setting, and Participants: This randomized clinical trial is a post hoc follow-up study that analyzes the results of the open-label Multicentre Randomized Controlled Phase III Trial, which enrolled patients from 13 different centers in France and was conducted from October 26, 2009, to April 4, 2012. Eligible patients were 18 to 75 years of age and were diagnosed with resectable cancer of the middle or lower third of the esophagus. After exclusions, patients were randomized to either the HMIE group or the open esophagectomy group. Data analysis was performed on an intention-to-treat basis from November 19, 2019, to December 4, 2020. Interventions: Hybrid minimally invasive esophagectomy (laparoscopic gastric mobilization with open right thoracotomy) was compared with open esophagectomy. Main Outcomes and Measures: The primary end points of this follow-up study were 5-year OS and DFS. The secondary end points were the site of disease recurrence and potential risk factors associated with DFS and OS. Results: A total of 207 patients were randomized, of whom 175 were men (85%), and the median (range) age was 61 (23-78) years. The median follow-up duration was 58.2 (95% CI, 56.5-63.8) months. The 5-year OS was 59% (95% CI, 48%-68%) in the HMIE group and 47% (95% CI, 37%-57%) in the open esophagectomy group (hazard ratio [HR], 0.71; 95% CI, 0.48-1.06). The 5-year DFS was 52% (95% CI, 42%-61%) in the HMIE group vs 44% (95% CI, 34%-53%) in the open esophagectomy group (HR, 0.81; 95% CI, 0.55-1.17). No statistically significant difference in recurrence rate or location was found between groups. In a multivariable analysis, major intraoperative and postoperative complications (HR, 2.21; 95% CI, 1.41-3.45; P < .001) and major pulmonary complications (HR, 1.94; 95% CI, 1.21-3.10; P = .005) were identified as risk factors associated with decreased OS. Similarly, multivariable analysis of DFS identified overall intraoperative and postoperative complications (HR, 1.93; 95% CI, 1.28-2.90; P = .002) and major pulmonary complications (HR, 1.85; 95% CI, 1.19-2.86; P = .006) as risk factors. Conclusions and Relevance: This study found no difference in long-term survival between the HMIE and open esophagectomy groups. Major postoperative overall complications and pulmonary complications appeared to be independent risk factors in decreased OS and DFS, providing additional evidence that HMIE may be associated with improved oncological results compared with open esophagectomy primarily because of a reduction in postoperative complications. Trial Registration: ClinicalTrials.gov Identifier: NCT00937456.

Perineal Wound Closure Following Abdominoperineal Resection and Pelvic Exenteration for Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Abdominoperineal resection (APR) and pelvic exenteration (PE) for the treatment of cancer require extensive pelvic resection with a high rate of postoperative complications. The objective of this work was to systematically review and meta-analyze the effects of vertical rectus abdominis myocutaneous flap (VRAMf) and mesh closure on perineal morbidity following APR and PE (mainly for anal and rectal cancers). METHODS: We searched PubMed, Cochrane, and EMBASE for eligible studies as of the year 2000. After data extraction, a meta-analysis was performed to compare perineal wound morbidity. The studies were distributed as follows: Group A comparing primary closure (PC) and VRAMf, Group B comparing PC and mesh closure, and Group C comparing PC and VRAMf in PE. RESULTS: Our systematic review yielded 18 eligible studies involving 2180 patients (1206 primary closures, 647 flap closures, 327 mesh closures). The meta-analysis of Groups A and B showed PC to be associated with an increase in the rate of total (Group A: OR 0.55, 95% CI 0.43-0.71; p < 0.01/Group B: OR 0.54, CI 0.17-1.68; p = 0.18) and major perineal wound complications (Group A: OR 0.49, 95% CI 0.35-0.68; p < 0.001/Group B: OR 0.38, 95% CI 0.12-1.17; p < 0.01). PC was associated with a decrease in total (OR 2.46, 95% CI 1.39-4.35; p < 0.01) and major (OR 1.67, 95% CI 0.90-3.08; p = 0.1) perineal complications in Group C. CONCLUSION: Our results confirm the contribution of the VRAMf in reducing major complications in APR. Similarly, biological prostheses offer an interesting alternative in pelvic reconstruction. For PE, an adapted reconstruction must be proposed with specialized expertise.

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.

Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1: A GTE and AFCE Cohort Study (Groupe d'étude des Tumeurs Endocrines and Association Francophone de Chirurgie Endocrinienne).

OBJECTIVE: To assess the distant metastatic potential of duodeno-pancreatic neuroendocrine tumors (DP-NETs) in patients with MEN1, according to functional status and size. SUMMARY BACKGROUND DATA: DP-NETs, with their numerous lesions and endocrine secretion-related symptoms, continue to be a medical challenge; unfortunately they can become aggressive tumors associated with distant metastasis, shortening survival. The survival of patients with large nonfunctional DP-NETs is known to be poor, but the overall contribution of DP-NETs to metastatic spread is poorly known. METHODS: The study population included patients with DP-NETs diagnosed after 1990 and followed in the MEN1 cohort of the Groupe d'étude des Tumeurs Endocrines (GTE). A multistate Markov piecewise constant intensities model was applied to separate the effects of prognostic factors on 1) metastasis, and 2) metastasis-free death or 3) death after appearance of metastases. RESULTS: Among the 603 patients included, 39 had metastasis at diagnosis of DP-NET, 50 developed metastases during follow-up, and 69 died. The Markov model showed that Zollinger-Ellison-related tumors (regardless of tumor size and thymic tumor pejorative impact), large tumors over 2 cm, and age over 40 years were independently associated with an increased risk of metastases. Men, patients over 40 years old and patients with tumors larger than 2 cm, also had an increased risk of death once metastasis appeared. CONCLUSIONS: DP-NETs of 2 cm in size or more, regardless of the associated secretion, should be removed to prevent metastasis and increase survival. Surgery for gastrinoma remains debatable.

Hepatitis E virus replication in human intestinal cells.

OBJECTIVE: Hepatitis E virus (HEV), one of the most common agent of acute hepatitis worldwide, is mainly transmitted enterically, via contaminated water for HEV genotypes 1 (HEV1) and HEV2, or by eating raw or undercooked infected meat for HEV genotype 3 (HEV3) and HEV4. However, little is known about how the ingested HEV reaches the liver or its ability to replicate in intestinal cells. DESIGN: We developed human primary cultures of small intestine epithelial cells and intestinal explants obtained from small bowel resections. The epithelial cells were also polarised on transwells. Cells were infected with Kernow-p6 strain or clinically derived virions. RESULTS: Primary intestinal cells supported the growth of Kernow-p6 strain and HEV1 and HEV3 clinically derived virions. Polarised enterocytes infected with HEV1 and HEV3 strains released HEV particles vectorially: mostly into the apical compartment with a little basally. Iodixanol density gradient centrifugation of enterocyte-derived HEV virions gave bands at a density of 1.06-1.08 g/cm3, corresponding to that of quasi-enveloped HEV particles. Ribavirin therapy inhibited HEV excretion from the basal surface but not from the apical side of infected human enterocytes. HEV virions also infected intestinal tissue explants. Lastly, HEV RNA and antigen were detected in the intestinal crypts of a chronically infected patient. CONCLUSION: HEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.

Health-related Quality of Life Following Hybrid Minimally Invasive Versus Open Esophagectomy for Patients With Esophageal Cancer, Analysis of a Multicenter, Open-label, Randomized Phase III Controlled Trial: The MIRO Trial.

BACKGROUND: Hybrid minimally invasive esophagectomy (HMIE) has been shown to reduce major postoperative complications compared with open esophagectomy (OE) for esophageal cancer. OBJECTIVES: The aim of this study was to compare short- and long-term health-related quality of life (HRQOL) following HMIE and OE within a randomized controlled trial. METHODS: We performed a multicenter, open-label, randomized controlled trial at 13 study centers between 2009 and 2012. Patients aged 18 to 75 years with resectable cancers of the middle or lower third of the esophagus were randomized to undergo either transthoracic OE or HMIE. Patients were followed-up every 6 months for 3 years postoperatively and global health assessed with EORTC-QLQC30 and esophageal symptoms assessed with EORTC-OES18. RESULTS: The short-term reduction in global HRQOL at 30 days specifically role functioning [-33.33 (HMIE) vs -46.3 (OE); P = 0.0407] and social functioning [-16.88 (HMIE) vs -35.74 (OE); P = 0.0003] was less substantial in the HMIE group. At 2 years, social functioning had improved following HMIE to beyond baseline (+5.37) but remained reduced in the OE group (-8.33) (P = 0.0303). At 2 years, increases in pain were similarly reduced in the HMIE compared with the OE group [+6.94 (HMIE) vs +14.05 (OE); P = 0.018]. Postoperative complications in multivariate analysis were associated with role functioning, pain, and dysphagia. CONCLUSIONS: Esophagectomy has substantial effects upon short-term HRQOL. These effects for some specific parameters are, however, reduced with HMIE, with persistent differences up to 2 years, and maybe mediated by a reduction in postoperative complications.

Synchronous liver metastases and peritoneal carcinomatosis from colorectal cancer: different strategies for curative treatment?

BACKGROUND: Management of patients with resectable hepatic metastases (HMs) and colorectal peritoneal carcinomatosis (CRPC) is not currently standardised. OBJECTIVE: The aims of this study were to evaluate the safety of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and hepatic surgery for patients with CRPC with synchronous hepatic metastases (HM), and its impact on survival rates. METHODS: A retrospective analysis was performed, including patients undergoing CRS/HIPEC for CRPC from 2007 to September 2016 in two groups, with (HM+) and without (HM-) synchronous hepatic metastases. Patients with extra-abdominal metastases were excluded. The hepatic strategy was described. Morbimortality and survival were compared between the two groups. RESULTS: One hundred nine patients underwent CRS/HIPEC for CRPC with or without hepatic surgery with curative intent: 33 patients with (HM+) and 76 patients without (HM-) synchronous HM. The median follow-up was 30 months. All patients with HM (HM+) received neoadjuvant chemotherapy vs. 88.1% in the HM- group (p = 0.04) associated with monoclonal antibody in 66.6% of cases in the HM+ group vs. 57% in the HM- group (p = 0.01). In the HM+ group, two steps were implemented to treat peritoneal and hepatic metastases in 15 patients (45%). In this group, planned hepatic resection in two procedures was performed for eight patients, all presenting bilobar HM. Postoperative morbidity did not differ between the two groups. No deaths occurred. Median overall survival (OS) and recurrence-free survival (RFS) were 31 and 65 months (p = 0.188), versus 21 and 24 months (p = 0.119), respectively, in the HM+ versus HM- groups. In multivariate analysis, the peritoneal cancer index (PCI) was the only significant prognostic factor whereas synchronous HM was not a significant prognostic factor. CONCLUSION: Curative surgical treatment for CRPC with synchronous HM seems to be feasible and safe, and could facilitate long survival rates, compared to patients without HM. The hepatic strategy is not standardised. However, a "two-step" surgical strategy could be proposed in order to reduce postoperative morbidity rates.

Hiatal hernia after oesophagectomy: a large European survey.

OBJECTIVES: Hiatal hernias (HH) after oesophagectomy are rare, and their surgical management is not well standardized. Our goal was to report on the management of HH after oesophagectomy in high-volume tertiary European French-speaking centres. METHODS: We conducted a retrospective multicentre study among 19 European French-speaking departments of upper gastrointestinal and/or thoracic surgery. All patients scheduled or operated on for the repair of an HH after oesophagectomy were collected between 2000 and 2016. Demographics, details of the initial procedure, surgical management and long-term outcome were analysed. RESULTS: Seventy-nine of 6608 (1.2%) patients who had oesophagectomies were included in the study. The postoesophagectomy diagnostic interval of an HH after oesophagectomy was ≤90 days (n = 17; 21%), 13 were emergency cases; between 91 days and 1 year, n = 21 (27%), 13 in emergency; ≥1 year, n = 41 (52%), 17 in emergency. The time to occurrence of HH after oesophagectomy was shorter after laparoscopy (median 308 days; interquartile range 150-693) compared to that after laparotomy (median 562 days, interquartile range 138-1768; P = 0.01). The incidence of HH after oesophagectomy was 0.73% (22/3010) after open surgery and 1.4% (26/1761) after laparoscopy (P = 0.03). Among the 79 patients, 78 were operated on: 35 had laparotomies (45%), 19 had laparoscopies (24%) and 24 (31%) had transthoracic approaches. Among the 43 urgent surgeries, 35 were open (25 laparotomies and 10 transthoracic approaches) and 8 were laparoscopies (conversion rate, 25%). Nine patients required bowel resections. Morbidity occurred in 36 (46%) patients with 1 postoperative death (1.2%). During the follow-up period, recurrent HH after oesophagectomy requiring revisional surgery developed in 8 (6 days-26 months) patients. CONCLUSIONS: Surgical management of HH after oesophagectomy could be done by laparoscopy in patients with scheduled surgery but laparotomy or thoracotomy was preferred in urgent situations. The incidence of HH after oesophagectomy is higher and its onset earlier when laparoscopy is used at the initial oesophagectomy.

Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer.

BACKGROUND: Postoperative complications, especially pulmonary complications, affect more than half the patients who undergo open esophagectomy for esophageal cancer. Whether hybrid minimally invasive esophagectomy results in lower morbidity than open esophagectomy is unclear. METHODS: We performed a multicenter, open-label, randomized, controlled trial involving patients 18 to 75 years of age with resectable cancer of the middle or lower third of the esophagus. Patients were randomly assigned to undergo transthoracic open esophagectomy (open procedure) or hybrid minimally invasive esophagectomy (hybrid procedure). Surgical quality assurance was implemented by the credentialing of surgeons, standardization of technique, and monitoring of performance. Hybrid surgery comprised a two-field abdominal-thoracic operation (also called an Ivor-Lewis procedure) with laparoscopic gastric mobilization and open right thoracotomy. The primary end point was intraoperative or postoperative complication of grade II or higher according to the Clavien-Dindo classification (indicating major complication leading to intervention) within 30 days. Analyses were done according to the intention-to-treat principle. RESULTS: From October 2009 through April 2012, we randomly assigned 103 patients to the hybrid-procedure group and 104 to the open-procedure group. A total of 312 serious adverse events were recorded in 110 patients. A total of 37 patients (36%) in the hybrid-procedure group had a major intraoperative or postoperative complication, as compared with 67 (64%) in the open-procedure group (odds ratio, 0.31; 95% confidence interval [CI], 0.18 to 0.55; P<0.001). A total of 18 of 102 patients (18%) in the hybrid-procedure group had a major pulmonary complication, as compared with 31 of 103 (30%) in the open-procedure group. At 3 years, overall survival was 67% (95% CI, 57 to 75) in the hybrid-procedure group, as compared with 55% (95% CI, 45 to 64) in the open-procedure group; disease-free survival was 57% (95% CI, 47 to 66) and 48% (95% CI, 38 to 57), respectively. CONCLUSIONS: We found that hybrid minimally invasive esophagectomy resulted in a lower incidence of intraoperative and postoperative major complications, specifically pulmonary complications, than open esophagectomy, without compromising overall and disease-free survival over a period of 3 years. (Funded by the French National Cancer Institute; ClinicalTrials.gov number, NCT00937456 .).