Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability.

Microsatellite instability in colorectal cancer predicts favorable outcomes. However, the mechanistic relationship between microsatellite instability, tumor-infiltrating immune cells, Immunoscore, and their impact on patient survival remains to be elucidated. We found significant differences in mutational patterns, chromosomal instability, and gene expression that correlated with patient microsatellite instability status. A prominent immune gene expression was observed in microsatellite-instable (MSI) tumors, as well as in a subgroup of microsatellite-stable (MSS) tumors. MSI tumors had increased frameshift mutations, showed genetic evidence of immunoediting, had higher densities of Th1, effector-memory T cells, in situ proliferating T cells, and inhibitory PD1-PDL1 cells, had high Immunoscores, and were infiltrated with mutation-specific cytotoxic T cells. Multivariate analysis revealed that Immunoscore was superior to microsatellite instability in predicting patients' disease-specific recurrence and survival. These findings indicate that assessment of the immune status via Immunoscore provides a potent indicator of tumor recurrence beyond microsatellite-instability staging that could be an important guide for immunotherapy strategies.

SafeHeal Colovac Colorectal Anastomosis Protection Device evaluation (SAFE-2) pivotal study: an international randomized controlled study to evaluate the safety and effectiveness of the Colovac Colorectal Anastomosis Protection Device.

AIM: Although proximal faecal diversion is standard of care to protect patients with high-risk colorectal anastomoses against septic complications of anastomotic leakage, it is associated with significant morbidity. The Colovac device (CD) is an intraluminal bypass device intended to avoid stoma creation in patients undergoing low anterior resection. A preliminary study (SAFE-1) completed in three European centres demonstrated 100% protection of colorectal anastomoses in 15 patients, as evidenced by the absence of faeces below the CD. This phase III trial (SAFE-2) aims to evaluate the safety and effectiveness of the CD in a larger cohort of patients undergoing curative rectal cancer resection. METHODS: SAFE-2 is a pivotal, multicentre, prospective, open-label, randomized, controlled trial. Patients will be randomized in a 1:1 ratio to either the CD arm or the diverting loop ileostomy arm, with a recruitment target of 342 patients. The co-primary endpoints are the occurrence of major postoperative complications within 12 months of index surgery and the effectiveness of the CD in reducing stoma creation rates. Data regarding quality of life and patient's acceptance and tolerance of the device will be collected. DISCUSSION: SAFE-2 is a multicentre randomized, control trial assessing the efficacy and the safety of the CD in protecting low colorectal anastomoses created during oncological resection relative to standard diverting loop ileostomy. TRIAL REGISTRATION: NCT05010850.

Effect of opioid-free anesthesia on post-operative period in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a propensity score matched study.

BACKGROUND: Postoperative pain after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is important. It appears essential to reduce postoperative pain and morphine consumption. METHODS: Retrospective study in a university hospital comparing patient benefiting from CRS-HIPEC under opioid-free anesthesia (OFA; dexmedetomidine) to those anesthetized with opioid anesthesia (OA; remifentanil) using a propensity score matching method. The main objective was the impact of OFA on postoperative morphine consumption in the first 24 h after surgery. RESULTS: 102 patients were included, matching on the propensity score allowed selecting 34 unique pairs analyzed. Morphine consumption was lower in the OFA group than in the OA group (3.0 [0.00-11.0] mg/24 h vs. 13.0 [2.5-25.0] mg/24 h; p = 0.02). In multivariable analysis, OFA was associated with a reduction of 7.2 [0.5-13.9] mg of postoperative morphine (p = 0.04). The rate of renal failure with a KDIGO-score > 1 was lower in the OFA group than in the OA group (12% vs. 38%; p = 0.01). There was no difference between groups concerning length of surgery/anesthesia, norepinephrine infusion, volume of fluid therapy, post-operative complications, rehospitalization or ICU readmission within 90 days, mortality, and postoperative rehabilitation. CONCLUSION: Our results suggest that OFA for CRS-HIPEC patients appears safe and is associated with less postoperative morphine use and acute kidney injury.

Is Delaying a Coloanal Anastomosis the Ideal Solution for Rectal Surgery?: Analysis of a Multicentric Cohort of 564 Patients From the GRECCAR.

OBJECTIVES: To assess the specific results of delayed coloanal anastomosis (DCAA) in light of its 2 main indications. BACKGROUND: DCAA can be proposed either immediately after a low anterior resection (primary DCAA) or after the failure of a primary pelvic surgery as a salvage procedure (salvage DCAA). METHODS: All patients who underwent DCAA intervention at 30 GRECCAR-affiliated hospitals between 2010 and 2021 were retrospectively included. RESULTS: Five hundred sixty-four patients (male: 63%; median age: 62 years; interquartile range: 53-69) underwent a DCAA: 66% for primary DCAA and 34% for salvage DCAA. Overall morbidity, major morbidity, and mortality were 57%, 30%, and 1.1%, respectively, without any significant differences between primary DCAA and salvage DCAA ( P = 0.933; P = 0.238, and P = 0.410, respectively). Anastomotic leakage was more frequent after salvage DCAA (23%) than after primary DCAA (15%), ( P = 0.016).Fifty-five patients (10%) developed necrosis of the intra-abdominal colon. In multivariate analysis, intra-abdominal colon necrosis was significantly associated with male sex [odds ratio (OR) = 2.67 95% CI: 1.22-6.49; P = 0.020], body mass index >25 (OR = 2.78 95% CI: 1.37-6.00; P = 0.006), and peripheral artery disease (OR = 4.68 95% CI: 1.12-19.1; P = 0.030). The occurrence of this complication was similar between primary DCAA (11%) and salvage DCAA (8%), ( P = 0.289).Preservation of bowel continuity was reached 3 years after DCAA in 74% of the cohort (primary DCAA: 77% vs salvage DCAA: 68%, P = 0.031). Among patients with a DCAA mannered without diverting stoma, 75% (301/403) have never required a stoma at the last follow-up. CONCLUSIONS: DCAA makes it possible to definitively avoid a stoma in 75% of patients when mannered initially without a stoma and to save bowel continuity in 68% of the patients in the setting of failure of primary pelvic surgery.

Delaying Surgery After Neoadjuvant Chemotherapy Affects Survival in Patients with Colorectal Peritoneal Metastases: A BIG-RENAPE Network Multicentric Study.

BACKGROUND: Multimodal treatment for patients with peritoneal metastases (PM) from colorectal cancer (CRC), including perioperative chemotherapy (CT) plus complete resection, is associated with prolonged survival. The oncologic impact of therapeutic delays is unknown. OBJECTIVE: The aim of this study was to assess the survival impact of delaying surgery and CT. METHODS: Medical records from the national BIG RENAPE network database of patients with complete cytoreductive (CC0-1) surgery of synchronous PM from CRC who received at least one neoadjuvant CT cycle plus one adjuvant CT cycle were retrospectively reviewed. The optimal interval between the end of neoadjuvant CT to surgery, surgery to adjuvant CT, and total interval without systemic CT were estimated using Contal and O'Quigley's method plus restricted cubic spline methods. RESULTS: From 2007 to 2019, 227 patients were identified. After a median follow-up of 45.7 months, the median overall survival (OS) and progression-free survival (PFS) was 47.6 and 10.9 months, respectively. The best cut-off period was 42 days in the preoperative interval, no cut-off period was optimal in the postoperative interval, and the best cut-off period in the total interval without CT was 102 days. In multivariate analysis, age, biologic agent use, high peritoneal cancer index, primary T4 or N2 staging, and delay to surgery of more than 42 days (median OS 63 vs. 32.9 months; p = 0.032) were significantly associated with worse OS. Preoperative delay of surgery was also significantly associated with PFS, but only in univariate analysis. CONCLUSION: In selected patients undergoing complete resection plus perioperative CT, a period of more than 6 weeks from completion of neoadjuvant CT to cytoreductive surgery was independently associated with worse OS.

Local excision after neoadjuvant chemoradiotherapy for mid and low rectal cancer: a multicentric French study from the GRECCAR group.

AIM: A complete or subcomplete tumour response (CTR) is observed in 10%-25% of patients with mid/low rectal cancer after neoadjuvant chemoradiotherapy (CRT). The aim of our study was to report a multicentric French experience in local excision (LE) after CRT. METHOD: All patients who underwent LE for mid/low rectal cancer with suspected CTR after CRT, from 2006 to 2019 in seven GRECCAR centres were included. LE was considered adequate if the specimen showed a ypT0/Tis/T1R0 tumour, otherwise, a completion total mesorectal excision (TME) was discussed. Morbi-mortality, functional results and oncological outcomes were studied. RESULTS: A total of 257 patients were included. LE specimens showed 36% ypT0, 4% ypTis and 19% ypT1. Thus, 108 patients (42%) had theoretical indication of completion TME, which was performed in only 42 patients. Overall, 30-day morbidity after LE was 11%, including 2% Clavien-Dindo grade III or IV complications. After completion TME, 47% described major low anterior resection syndrome versus 5% after LE alone (p < 0.001). After a mean follow-up of 4 years (range 2-6 years), the recurrence rate was 11% after LE, 32% after completion TME and 20% in patients for whom completion TME was indicated but not performed (p = 0.021). CONCLUSION: TME remains the gold standard for mid/low rectal cancer after CRT. LE in selected patients is safe for operative and functional, but also oncological, results. However, completion TME was indicated in 42% of patients after LE, highlighting the difficulty of the preoperative diagnosis of CTR after CRT.

Iatrogenic ureteral injury during colorectal surgery has a significant impact on patient outcomes: a French multicentric retrospective cohort study.

AIM: The long-term urological sequelae after iatrogenic ureteral injury (IUI) during colorectal surgery are not clearly known. The aims of this work were to report the incidence of IUI and to analyse the long-term consequences of urological late complications and their impact on oncological results of IUI occurring during colorectal surgery through a French multicentric experience (GRECCAR group). METHOD: All the patients who presented with IUI during colorectal surgery between 2010 and 2019 were retrospectively included. Patients with ureteral involvement needing en bloc resection, delayed ureteral stricture or noncolorectal surgery were not considered. RESULTS: A total of 202 patients (93 men, mean age 63 ± 14 years) were identified in 29 centres, corresponding to 0.32% of colorectal surgeries (n = 63 562). Index colorectal surgery was mainly oncological (n = 130, 64%). IUI was diagnosed postoperatively in 112 patients (55%) after a mean delay of 11 ± 9 days. Intraoperative diagnosis of IUI was significantly associated with shorter length of stay (21 ± 22 days vs. 34 ± 22 days, p < 0.0001), lower rates of postoperative hydronephrosis (2% vs. 10%, p = 0.04), anastomotic complication (7% vs. 22.5%, p = 0.002) and thromboembolic event (0% vs. 6%, p = 0.02) than postoperative diagnosis of IUI. Delayed chemotherapy because of IUI was reported in 27% of patients. At the end of the follow-up [3 ± 2.6 years (1 month-13 years)], 72 patients presented with urological sequalae (36%). Six patients (3%) required a nephrectomy. CONCLUSION: IUI during colorectal surgery has few consequences for the patients if recognized early. Long-term urological sequelae can occur in a third of patients. IUI may affect oncological outcomes in colorectal surgery by delaying adjuvant chemotherapy, especially when the ureteral injury is not diagnosed peroperatively.

Can the Realization of an External Wirsungostomy be an Option for High-Risk Pancreatic Anastomosis After Pancreaticoduodenectomy?

BACKGROUND: Clinically relevant postoperative pancreatic fistula (POPF) occurs in 15-20% of patients after pancreaticoduodenectomy (PD) and reintervention in the setting of Grade C POPF remains associated with a mortality rate of up to 25%. In patients at high risk of POPF, PD with external wirsungostomy (EW) could be a safe alternative that avoids pancreatico-enteric anastomosis while preserving the remnant pancreas. METHODS: Of the 155 consecutive patients who underwent PD from November 2015 to December 2020, 10 patients were managed using an EW, all with a fistula risk score (FRS) ≥ 7 and BMI ≥30 kg/m2, and/or major associated abdominal surgery. The pancreatic duct was cannulated with a polyethylene tube to allow good external drainage of the pancreatic fluid. We retrospectively analyzed postoperative complications and endocrine and exocrine insufficiencies. RESULTS: The median alternative FRS was 36.9% [22.1-45.2]. There was no postoperative death. The 90-day overall severe complication (grade ≥3) rate was 30% (n = 3 patients), no patient required reoperation, and 2 hospital readmissions occurred. 3 patients experienced Grade B POPF (30%), managed using image-guided drainage for 2 patients. The external pancreatic drain was removed after a median drainage time of 75 days [63-80]. Two patients presented with late symptoms (> 6 months) warranting interventional management (pancreaticojejunostomy and transgastric drainage). Six patients experienced significant weight loss (> 2 kg) 3 months after surgery. One year after surgery, 4 patients still complained of diarrhea and were treated with transit-delaying drugs. One patient presented new-onset diabetes one year after surgery, and 1 of the 4 patients with preexisting diabetes experienced worsening disease. CONCLUSION: EW after PD might be a solution to reduce post-operative mortality following PD in high-risk patients.

Disk Excision Using End-to-End Anastomosis Circular Stapler for Deep Endometriosis of the Rectum: A 492-Patient Continuous Prospective Series.

STUDY OBJECTIVE: To report a large series including women managed by disk excision using end-to-end anastomosis (EEA) circular transanal stapler to assess the feasibility of the technique, the features of nodules suitable for removal by disk excision, and the rate of major early complications. DESIGN: Retrospective study on data prospectively recorded in 2 databases. SETTING: Two tertiary referral centers. PATIENTS: A total of 492 patients undergoing surgery for rectal endometriosis from May 2011 to June 2022. INTERVENTIONS: Rectal disk excision using the EEA stapler. MEASUREMENT AND MAIN RESULTS: Disk excision using EEA was performed in 492 patients (24.2%) of 2,029 women receiving surgery for deep endometriosis infiltrating the rectum during the 11-year study period. Deep endometriosis involved low rectum in 11% and mid rectum in 55.3%. The diameter of rectal nodules exceeded 3 cm in 65.9%. Mean operative time was 2 hours, mean diameter of rectal patches removed was 41 ± 11 mm, and the mean rectal suture height was 9.2 ± 5.5 cm. The presence of microscopic foci on the edges of rectal patches was identified in 30.2% of cases. Rectal fistula was recorded in 20 patients (4%). The distance from the anal verge was significantly lower in patients with fistula than women with no fistula (5.9 ± 2 cm vs 9.2 ± 5.6 cm, p = .027). Follow-up ranged from 1 to 120 months, with a median value of 36 months. Magnetic resonance imaging in 3 patients during follow-up revealed a recurrent nodule infiltrating the previous stapled line (0.6%) after a postoperative delay of, respectively, 36, 48, and 84 months. CONCLUSION: Disk excision using the EEA stapler is suitable in nodules >3 cm if surgeons ensure deep shaving of the rectum, to allow complete inclusion of the shaved area into the stapler jaws. Postoperative rectal recurrences seem incidental, whereas bowel leakage rate is comparable with that after colorectal resection. This technique is suitable in almost a quarter of patients managed for rectal endometriosis nodules and is therefore a valuable technique that warrants more widespread use.

Circulating DNA changes are predictive of disease progression after transarterial chemoembolization.

Transarterial chemoembolization (TACE) is used to treat patients with unresectable hepatocellular carcinoma (HCC). We evaluated the clinical impact of a-fetoprotein (AFP) and circulating cell-free and tumor DNA (cfDNA and ctDNA) changes around the TACE procedure. Our prospective monocentric study enrolled consecutive patients treated with TACE, with samples collected at baseline (D - 1), Day 2 (D + 2) and 1 month (M + 1) after TACE. cfDNA was quantified by the fluorometric method, and ctDNA was quantified by digital polymerase chain reaction designed for two hotspot TERT mutations. Computerized tomography scans or magnetic resonance imaging were performed at M + 1 every 3 months following TACE and independently reviewed. The objective was to identify thresholds of cfDNA, ctDNA and AFP changes associated with progressive disease (PD) using receiver operating characteristic curves. Thirty-eight patients were included from March 2018 to March 2019. All markers significantly increased from D - 1 to D + 2 (P < .005), and cfDNA and ctDNA significantly decreased from D + 2 to M + 1 (P < .0001). The analysis of changes from D - 1 to M + 1 identified thresholds at +31.4% for cfDNA and 0% for ctDNA that were significantly associated with PD at M + 1 (44.4% [>+31.4%] vs 3.8% [≤+31.4%] and 50.0% [>0%] vs 5.0% [≤0%], respectively). No significant threshold was identified for AFP. Using a score combining cfDNA and ctDNA, the patients were classified into high- or low-risk PD groups at M + 1, with PD rates of 80.0% vs 4.3% (P = .001) and median progression-free survival times of 1.3 vs 10.3 months (P = .002). Our study suggests that cfDNA and ctDNA increases around the TACE procedure and are associated with therapeutic failure.

Tailored Strategy for Locally Advanced Rectal Carcinoma (GRECCAR 4): Long-term Results From a Multicenter, Randomized, Open-Label, Phase II Trial.

BACKGROUND: Systematic preoperative radiochemotherapy and total mesorectal excision are the standard of care for locally advanced rectal carcinoma. Some patients can be over- or undertreated. OBJECTIVE: This study aimed to investigate the long-term oncological, functional, and late morbidity outcomes after tailored radiochemotherapy and induction high-dose chemotherapy. DESIGN: This is a prospective, phase II, multicenter, open-label study at 16 tertiary centers in France. SETTINGS: Patients were operated on by surgeons from the French GRECCAR group. PATIENTS: Two hundred six patients were randomly assigned to treatment: good responders after chemotherapy (≥75% tumor volume reduction) to immediate surgery (arm A) or standard radiochemotherapy (capecitabine 50) plus surgery (arm B) and poor responders to capecitabine 50 (arm C) or intensive radiochemotherapy (capecitabine 60; 60 Gy irradiation; arm D) before surgery. INTERVENTIONS: Treatment was tailored according to MRI response to induction chemotherapy. RESULTS: After induction treatment, 194 patients were classified as good (n = 30, 15%) or poor (n = 164, 85%) responders; they were included in arms A and B (16 and 14 patients) or C and D (113 and 51 patients). The primary objective was obtained: R0 resection rates (90% CI) in the 4 arms were 100% (74-100), 100% (85-100), 83% (72-91), and 88% (77-95). At 5 years, overall survival rates were 90% (47.3-98.5), 93.3% (61.3-99.0), 84.3% (71.0-91.8), and 86.1% (71.6-93.5); disease-free survival rates were 80% (40.9-94.6), 89.5% (64.1-97.3), 72.9% (58.5-82.9), and 72.8% (57.7-83.2); local recurrence rates were 0%, 0%, 2.1% (0.3-13.9), and 9.3% (3.6-23.0); and metastasis rates were 20% (5.4-59.1), 10.5% (2.7-35.9), 18% (31.8-94.6), and 18.8% (10.2-33.0). Late morbidity and quality-of-life evaluations showed no significant difference between arms. LIMITATIONS: Limitations were due to the small number of patients randomly assigned in the good responder arms, especially arm A without radiotherapy. CONCLUSION: Tailoring preoperative radiochemotherapy based on induction treatment response appears to be promising. Future prospective trials should confirm this strategy. See Video Abstract at http://links.lww.com/DCR/B761 . REGISTRATION: URL: https://www.clinicaltrials.gov ; Identifier: NCT01333709. ESTRATEGIA HECHA A MEDIDA PARA EL TRATAMIENTO DEL CARCINOMA DE RECTO LOCALMENTE AVANZADO GRECCAR RESULTADOS A LARGO PLAZO DE UN ESTUDIO ALEATRIO MULTICNTRICO Y ABIERTO DE FASE II: ANTECEDENTES:La radio-quimioterapia pré-operatoria sistemáticas y la excisión total del mesorrecto son el estándar en el tratamiento del carcinoma de recto localmente avanzado. En éste sentido, algunos pacientes podrían recibir un sobre o un infra-tratamiento.OBJETIVO:Evaluar los resultados oncológicos, funcionales y de morbilidad a largo plazo después de radio-quimioterapia personalizada y quimioterapia de inducción a dosis elevadas.DISEÑO:Estudio aleatório multicéntrico y abierto de Fase II° realizado en 16 centros terciarios en Francia.AJUSTE:Aquellos pacientes operados por cirujanos del grupo GRECCAR francés.PACIENTES:206 pacientes fueron asignados aleatoriamente al tratamiento: los buenos respondedores después de quimioterapia (reducción del volumen tumoral ≥75%) a la cirugía inmediata (brazo A) o a la radio-quimioterapia estándar (Cap 50) asociada a la cirugía (brazo B); los malos respondedores a Cap 50 (brazo C) o a la radio-quimioterapia intensiva (Cap 60 (irradiación de 60 Gy) (brazo D) previas a la cirugía.INTERVENCIONES:Tratamiento adaptado según la respuesta de la RM a la TC de inducción.RESULTADOS:Después del tratamiento de inducción, 194 pacientes fueron clasificados como buenos (n = 30, 15%) o malos (n = 164, 85%) respondedores, y se incluyeron en los brazos A y B (16 y 14 pacientes) o C y D (113 y 51 pacientes). Se alcanzó el objetivo principal: las tasas de resección R0 [intervalo de confianza del 90%] en los cuatro brazos respectivamente, fueron del 100% [74-100], 100% [85-100], 83% [72-91] y 88% [77-95]. A los 5 años, las tasas fueron: de sobrevida global 90% [47,3-98,5], 93,3% [61,3-99,0], 84,3% [71,0-91,8], 86,1% [71,6-93,5]; de sobrevida libre a la enfermedad 80% [40,9-94,6], 89,5% [64,1-97,3], 72,9% [58,5-82,9], 72,8% [57,7-83,2]; de recidiva local 0, 0, 2,1% [0,3-13,9], 9,3% [3,6-23,0]; de metástasis 20% [5,4-59,1], 10,5% [2,7-35,9], 18% [31,8-94,6], 18,8% [10,2-33,0]. La evaluación tardía de la morbilidad y la calidad de vida no mostraron diferencias significativas entre los brazos.LIMITACIONES:Debido al pequeño número de pacientes asignados al azar en los brazos de buenos respondedores, especialmente en el brazo A de aquellos sin radioterapia.CONCLUSIÓN:Parecería muy prometedor el adaptar la radio-quimioterapia pré-operatoria basada en la respuesta al tratamiento de inducción. Estudios prospectivos en el futuro podrán confirmar la presente estrategia. Consulte Video Resumen en http://links.lww.com/DCR/B761 . (Traducción-Dr. Xavier Delgadillo )IDENTIFICADOR DE CLINICALTRIALS.GOV:NCT01333709. Groupe de REcherche Chirurgicale sur le CAncer du Rectum.

What Is the Optimal Elective Colectomy for Splenic Flexure Cancer: End of the Debate? A Multicenter Study From the GRECCAR Group With a Propensity Score Analysis.

BACKGROUND: The optimal elective colectomy in patients with splenic flexure tumor is debated. OBJECTIVE: This study aimed to compare splenic flexure colectomy, left hemicolectomy, and subtotal colectomy for perioperative, histological, and survival outcomes in this setting. DESIGN: This is a multicenter retrospective cohort study. SETTING: Patients diagnosed with nonmetastatic splenic flexure tumor who underwent elective colectomy were included. PATIENTS: Between 2006 and 2014, 313 consecutive patients were operated on in 15 French Research Group of Rectal Cancer Surgery centers. INTERVENTIONS: Propensity score weighting was performed to compare short- and long-term outcomes. MAIN OUTCOME MEASURES: The primary end point was disease-free survival. Secondary end points included overall survival, quality of surgical resection, overall postoperative morbidity, surgical postoperative morbidity, and rate of anastomotic leakage. RESULTS: The most performed surgery was splenic flexure colectomy (59%), followed by subtotal colectomy (23%) and left hemicolectomy (18%). Subtotal colectomy was more often performed by laparotomy compared with splenic flexure colectomy and left hemicolectomy (93% vs 61% vs 56%, p < 0.0001), and was associated with a longer operative time (260 minutes (120-460) vs 180 minutes (68-440) vs 217 minutes (149-480), p < 0.0001). Postoperative morbidity was similar between the 3 groups, but the median length of hospital stay was significantly longer after subtotal colectomy (13 days (5-56) vs 10 (4-175) vs 9 (4-55), p = 0.0007). The median number of harvested lymph nodes was significantly higher after subtotal colectomy compared with splenic flexure colectomy and left hemicolectomy (24 (8-90) vs 15 (1-81) vs 16 (3-52), p < 0.0001). The rate of stage III disease and the number of patients treated by adjuvant chemotherapy were similar between the 3 groups. There was no difference in terms of disease-free survival and overall survival between the 3 procedures. LIMITATIONS: The study was limited by its retrospective design. CONCLUSIONS: In the elective setting, splenic flexure colectomy is safe and oncologically adequate for patients with nonmetastatic splenic flexure tumor. However, given the oncological clearance after splenic flexure colectomy, it seems that the debate is not completely closed. See Video Abstract at http://links.lww.com/DCR/B703. CUL ES LA COLECTOMA ELECTIVA PTIMA PARA EL CNCER DE NGULO ESPLNICO FIN DEL DEBATE UN ESTUDIO MULTICNTRICO DEL GRUPO GRECCAR CON UN ANLISIS DE PUNTAJE DE PROPENSIN: ANTECEDENTES:La colectomía electiva óptima en pacientes con tumores del ángulo esplénico continua en debate.OBJETIVO:Comparar la colectomía de ángulo esplénico, hemicolectomía izquierda y colectomía subtotal para los resultados perioperatorios, histológicos y de supervivencia en este escenario.DISEÑO:Estudio de cohorte retrospectivo multicéntrico.ESCENARIO:Se incluyeron pacientes diagnosticados de tumores del ángulo esplénico no metastásicos que se sometieron a colectomía electiva.PACIENTES:Entre 2006 y 2014, 313 pacientes consecutivos fueron intervenidos en 15 centros GRECCAR.INTERVENCIONES:Se realizó una ponderación del puntaje de propensión para comparar los resultados a corto y largo plazo.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la supervivencia libre de enfermedad. Los criterios de valoración secundarios incluyeron la supervivencia general, la calidad de la resección quirúrgica, la morbilidad posoperatoria general, la morbilidad posoperatoria quirúrgica y la tasa de fuga anastomótica.RESULTADOS:La cirugía más realizada fue la colectomía del ángulo esplénico (59%), seguida de la colectomía subtotal (23%) y la hemicolectomía izquierda (18%). La colectomía subtotal se realizó con mayor frecuencia mediante laparotomía en comparación con la colectomía de ángulo esplénico y la hemicolectomía izquierda (93% frente a 61% frente a 56%, p <0.0001), y se asoció con un tiempo quirúrgico más prolongado (260 min [120-460] frente a 180 min [68-440] frente a 217 min [149-480], p <0.0001). La morbilidad posoperatoria fue similar entre los tres grupos, pero la duración media de la estancia hospitalaria fue significativamente más prolongada después de la colectomía subtotal (13 días [5-56] frente a 10 [4-175] frente a 9 [4-55], p = 0.0007). La mediana del número de ganglios linfáticos extraídos fue significativamente mayor después de la colectomía subtotal en comparación con la colectomía del ángulo esplénico y la hemicolectomía izquierda (24 [8-90] frente a 15 [1-81] frente a 16 [3-52], p <0.0001). La tasa de enfermedad en estadio III y el número de pacientes tratados con quimioterapia adyuvante fueron similares entre los 3 grupos. No hubo diferencias en términos de supervivencia libre de enfermedad y supervivencia general entre los 3 procedimientos.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:En un escenario electivo, la colectomía del ángulo esplénico es segura y oncológicamente adecuada para pacientes con tumores del ángulo esplénico no metastásicos. Sin embargo, dado el aclaramiento oncológico tras la colectomía del ángulo esplénico, parece que el debate no está completamente cerrado. Consulte Video Resumen en http://links.lww.com/DCR/B703.

Impact of a procalcitonin-based algorithm on the quality of management of patients with uncomplicated adhesion-related small bowel obstruction assessed by a textbook outcome: a multicenter cluster-randomized open-label controlled trial.

BACKGROUND: Acute adhesion-related small bowel obstruction (ASBO) is a common digestive emergency, accounting for 1 to 3% of all digestive emergencies. The efficacy of conservative management in this setting is a subject of debate, as it may delay the decision to perform surgery and increase the frequency of bowel resection (e.g., in the presence of bowel necrosis) or, in contrast, prompt an excessive number of unnecessary laparotomies. Thus, the decision to perform surgery is difficult. We propose that the introduction of the procalcitonin (PCT)-based algorithm improves the quality of the management of patients with ASBO by aiding the decision of whether or not to perform surgery. METHODS: This is a 1:1 cluster-randomized clinical trial (use of algorithm: no algorithm) using an independent computer to ensure that investigators cannot interfere with the randomization. Each cluster will correspond to one investigating center. All patients in a center will be managed in the same way. Before randomization, each principal investigator will provide a commitment to participate in the study to avoid the risk of "empty clusters". The patients included will constitute two parallel arms (use of algorithm versus no algorithm), with no expected crossover between arms. The inclusion criteria are being an adult with uncomplicated acute ASBO (i.e., absence of fever, abdominal pain and distension, nausea and/or vomiting, and the absence of gas and/or stool, in conjunction with a contrast-enhanced CT scan, for patients with previous abdominal surgery) who is able to express consent with a signed written informed consent form. Patients with complicated acute ASBO (strangulation or peritonitis) will be excluded. DISCUSSION: There is an ongoing debate on the management of uncomplicated ASBO. The main points are to avoid a surgery if it is unnecessary and to avoid delayed surgery if it is necessary. Currently, there are no robust criteria to objectively determine the failure of non-surgical treatment or to establish the indications for surgery in acute ASBO. Our team proposes the use of procalcitonin (PCT) to help distinguish patients for whom conservative management is likely to be successful from those for whom surgical management is required. The results from a randomized control trial could help in the selection of patients through clear inclusion and exclusion criteria and simplify or clarify the management algorithm. In conclusion, PCT may be useful in evaluating the proper strategy for ASBO. Trial registration The trial is registered at clinical trials under the reference: NCT03905239.

Is it safe to perform an anastomosis for rectal cancer after prostate cancer? A multicentre study of 126 patients from the GRECCAR group.

AIM: To determine the safety of performing an anastomosis after rectal cancer (RC) resection in patients with a previously treated prostate cancer (PC). METHODS: Patients with a previously treated PC who underwent rectal resection from 2008 to 2018 were retrospectively included. Outcomes were compared between patients who underwent rectal resection with anastomosis (restorative surgery, RS+ group) and those with a definitive stoma (RS- group). In the RS+ group, anastomotic leak (AL) rates were assessed according to the type of reconstruction. RESULTS: A total of 126 patients underwent rectal surgery for mid-low RC after a previous PC treated by radiotherapy (RT) and/or radical prostatectomy. Overall, 80 patients (63%) underwent a RS and 46 patients (37%) underwent rectal surgery with a definitive stoma. There was no statistical difference between the two groups in terms of intraoperative data, except for the type of resection with more multivisceral resection in the RS- group (p < 0.01). In the RS+group, a diverting stoma was performed in 74% of cases. No difference between the two groups in terms of overall morbidity was found. In the RS+group (n = 80), 17 patients (21%) experienced AL. Of these, none was observed when delayed coloanal anastomosis was performed (p = 0.16). Long-term permanent stoma in the RS+ group was 16% (n = 13). CONCLUSION: Restorative surgery after resection for RC in patients with a previous history of RT and/or radical prostatectomy for PC is safe without additional morbidity. In selected patients for restorative surgery, performing delayed coloanal anastomosis may represent a promising option.

Influence of Probiotics Administration Before Liver Resection in Patients with Liver Disease: A Randomized Controlled Trial.

BACKGROUND: By inhibiting the growth of pathogenic bacteria and modulating the local intestinal immune system, probiotics may reduce bacterial translocation and systemic endotoxaemia, factors partially responsible for post-operative complications following liver resection for hepatocellular carcinoma in patients with cirrhosis. METHODS: Patients with resectable hepatocellular carcinoma developed in the setting of chronic liver disease were prospectively divided into two equal-sized groups: one receiving probiotic treatment 14 days prior to surgery and the other receiving placebo. The primary endpoint was the level of circulating endotoxins after hepatectomy. Secondary endpoints were systemic inflammation (inflammatory cytokine levels), post-operative liver function and overall post-operative complication rate. RESULTS: From May 2013 to December 2018, 64 patients were randomized, and 54 patients were included in the analysis, 27 in each arm. No significant change in endotoxin levels was observed over time in either group (P = 0.299). No difference between the groups in terms of post-operative liver function and overall complication rates was observed. The only differences observed were significant increases in the levels of TNFalpha (P = 0.019) and interleukin 1-b (P = 0.028) in the probiotic group in the post-operative period. CONCLUSION: Contrary to the modest data reported in the literature, the administration of probiotics before minor liver resection for hepatocellular carcinoma developed in the setting of compensated chronic liver disease does not seem to have an impact on circulating endotoxin levels or post-operative complication rates. TRIAL REGISTRATION: Trial registration: NCT02021253.

Methodological and ethical quality of surgical trials from 2016 to 2020.

PURPOSE: Randomized controlled trials (RCTs) are the gold standard tool used to evaluate therapeutic interventions. The published results showed that progress still needs to be made not only from a methodological point of view but also from an ethical point of view. The aim of this study was to evaluate the methodological and ethical qualities of randomized clinical trials in surgery over the last few years. METHODS: All of the articles chosen for review reported on randomized controlled surgical trials and were published in 10 international journals between 2016 and 2020. Eligible studies were identified, selected, and then evaluated based on a broad set of predetermined criteria. Methodological quality was evaluated using the Jadad scale, and ethical quality was evaluated using the Berdeu score. RESULTS: The methodological quality score (Jadad scale) ranged from 5 to 13, with a mean of 10.0 ± 1.54. The methodological quality was insufficient (score ≤ 9) for 162 trials (31.2%). The ethical quality score ranged from 0.25 to 1, with a mean of 0.8 ± 0.11. Fifty-two articles (10%) did not state that informed consent was requested from the participants, and 21 articles (4%) did not report either research ethics committee or institutional committee protocol approval. CONCLUSION: The randomized clinical surgical trials analyzed showed that they had satisfactory methods in only 70% of the cases and that they had respected the fundamental ethical principles in 90% of the cases. However, less than 8% of the studies reported planned interim analysis, prospectively defined stopping rules, and independent monitoring committee.

Long-term Outcomes Following Surgical Management of Rectal Endometriosis: Seven-year Follow-up of Patients Enrolled in a Randomized Trial.

STUDY OBJECTIVE: To compare functional outcomes, recurrence rate, and pregnancy likelihood in patients undergoing conservative or radical surgery for deep rectal endometriosis followed up for 7 years. DESIGN: Prospective study in a cohort of patients enrolled in a 2-arm randomized trial from March 2011 to August 2013. SETTING: A tertiary referral center. PATIENTS: Fifty-five patients with deep endometriosis infiltrating the rectum. INTERVENTIONS: Patients underwent either segmental resection or nodule excision via shaving or disk excision, depending on randomization that was performed preoperatively using sequentially numbered, opaque sealed envelopes. MEASUREMENTS AND MAIN RESULTS: The primary end point was the number of patients experiencing one of the following symptoms: constipation, frequent bowel movements, anal incontinence, or bladder dysfunction 24 months after surgery. The secondary end points were values of gastrointestinal and overall quality of life scores. The 7-year recurrence rates (new deep endometriosis nodules infiltrating the rectum) in the excision vs segmental resection arms were 7.4 % vs 0% (p = .24). One of the symptoms included in the definition of the primary outcomes was recorded in 55.6% vs 60.7% of patients (p = .79). However, 51.9% vs 53.6% of patients considered their bowel movements as normal (p = .99). An intention-to-treat comparison of overall quality of life scores did not find a difference between the 2 groups 7 years after surgery. At the end of the 7-year study period, 31 of 37 patients who tried to conceive were successful (83.8%), including 27 pregnancies (57.4%) resulting from natural conception and 20 pregnancies (42.6%) resulting from assisted reproductive technology procedures. The pregnancy rate was 82.4% vs 85% in the 2 arms (p = .99). A 75.7% live birth rate was recorded. At the end of the follow-up, there were 15 women with 1 child (40.5%) and 13 women with 2 children (35.1%). During the 7-year follow-up, the reoperation rates were 37% and 35.7%, respectively, in each arm (p = .84). Among the 27 reoperation procedures during the follow-up period, 11 (40.7%) were for postoperative complications, 7 (25.9%) were necessary before assisted reproductive technology management, 8 (29.6%) were for recurrent abdominal or pelvic pain, and 1 (3.7%) was for midline ventral hernia after pregnancy. CONCLUSION: Our study did not reveal a considerable difference in terms of digestive functional outcomes, recurrence rate, reoperation risk, and pregnancy likelihood when conservative and radical rectal surgeries for deep endometriosis were compared 7 years after surgery. The postoperative pregnancy rate observed in our series was high.

Risk of Rectovaginal Fistula in Women with Excision of Deep Endometriosis Requiring Concomitant Vaginal and Rectal Sutures, with or without Preventive Stoma: A Before-and-after Comparative Study.

STUDY OBJECTIVE: To assess whether a liberal policy of preventive stoma (LPS) reduces the rate of rectovaginal fistulas in women with excision of deep endometriosis requiring concomitant vaginal and rectal sutures in comparison with a more restrictive policy of preventive stoma (RPS) and to assess the risk factors for rectovaginal fistula. DESIGN: Retrospective before-and-after comparative study. SETTING: Two referral centers, one with an LPS and the other with an RPS. PATIENTS: A total of 363 patients with deep endometriosis infiltrating the rectum and the vagina. INTERVENTIONS: Rectal disc excision or colorectal resection concomitantly with vaginal excision. MEASUREMENTS AND MAIN RESULTS: Two hundred forty-one and 122 women received surgery at the LPS and RPS centers, respectively. The rate of preventive stomas was 71.4% at the LPS center (n = 172) and 30.3% at the RPS center (N = 37). Rectovaginal fistula was recorded in 31 cases (8.5%): nineteen women were managed at the LPS center, and 12 women underwent surgery at the RPS center. It occurred in, respectively, 9.4%, 10.8%, 10.1%, and 7% of the women managed without and with a stoma at the RPS center and of those managed without and with a stoma at the LPS center (p = .72). The height of the rectal stapled line was significantly lower in the women undergoing a stoma, particularly in those managed at the RPS center (5.4 ± 1.8 cm). Performing rectal sutures within 8 cm from the anal verge increased the risk of rectovaginal fistula more than 3-fold, independently of stoma creation, surgical procedure carried out on the rectum, size of vaginal infiltration, or associated excision of deep endometriosis involving the pelvic nerves (odds ratio 3.4; 95% confidence interval, 1.3-9.1). CONCLUSION: No statistically significant differences were found in terms of the risk of rectovaginal fistula between women with rectovaginal endometriosis managed by either an LPS or an RPS; however, these findings need to be confirmed by a randomized trial.

Evolution of Bowel Complaints after Laparoscopic Endometriosis Surgery: A 1497 Women Comparative Study.

STUDY OBJECTIVE: To assess to what degree can digestive symptoms improve after endometriosis surgery for different localizations. DESIGN: A comparative retrospective study employing data prospectively recorded in the North-West Inter-Regional Female Cohort for Patients with Endometriosis (CIRENDO) from June 2009 to November 2018. SETTING: Two referral centers. PATIENTS: A total of 1497 women undergoing surgery because of pelvic endometriosis were divided into 3 groups: superficial endometriosis (Group 1, n = 396), deep endometriosis sparing the bowel (Group 2, n = 337), and deep endometriosis involving the bowel (Group 3, n = 764). INTERVENTIONS: Surgery for endometriosis. MEASUREMENTS AND MAIN RESULTS: Preoperative and postoperative gastrointestinal symptoms were evaluated with standardized questionnaires, including the Gastrointestinal Quality of Life Index (GIQLI) and Knowles-Eccersley-Scott-Symptom questionnaire (KESS). The degree of postoperative improvement in digestive symptoms was compared between the groups. The women in Group 3 were significantly symptomatic in terms of cycle-related gastrointestinal symptoms and scores of standardized questionnaires GIQLI and KESS. According to the 1-year postoperative evaluation, women in Group 3 experienced the most significant improvement in their gastrointestinal symptoms. CONCLUSION: Women with severe bowel symptoms and deep endometriosis infiltrating the bowel should be informed about the high probability of symptom improvement after the removal of bowel nodules. Conversely, in women without deep endometriosis, postoperatively, there is less improvement in baseline digestive complaints.

Role of protective stoma after primary anastomosis for generalized peritonitis due to perforated diverticulitis-DIVERTI 2 (a prospective multicenter randomized trial): rationale and design (nct04604730).

BACKGROUND: Traditionally, patients with peritonitis Hinchey III and IV due to perforated diverticulitis were treated with Hartmann's procedure. In the past decade, resection and primary anastomosis have gained popularity over Hartmann's procedure and recent guidelines recommend Hartmann's procedure in two situations only: critically ill patients and in selected patients with multiple comorbidity (at high risk of complications). The protective stoma (PS) is recommended after resection with primary anastomosis, however its interest has never been studied. The aim of this trial is to define the role of systematic PS after resection and primary anastomosis for peritonitis Hinchey III and IV due to perforated diverticulitis. METHODS/DESIGN: This DIVERTI 2 trial is a multicenter, randomized, controlled, superiority trial comparing resection and primary anastomosis with (control group) or without (experimental group) PS in patients with peritonitis Hinchey III and IV due to perforated diverticulitis. Primary endpoint is the overall 1 year morbidity according to the Clavien-Dindo classification of surgical complications. All complications occurring during hospitalization will be collected. Late complications occurring after hospitalization will be collected during follow-up. In order to obtain 80% power for a difference given by respective main probabilities of 67% and 47% in the protective stoma and no protective stoma groups respectively, with a two-sided type I error of 5%, 96 patients will have to be included in each group, hence 192 patients overall. Expecting a 5% rate of patients not assessable for the primary end point (lost to follow-up), 204 patients will be enrolled. Secondary endpoints are postoperative mortality, unplanned reinterventions, incisional surgical site infection (SSI), organ/space SSI, wound disruption, anastomotic leak, operating time, length of hospital stay, stoma at 1 year after initial surgery, quality of life, costs and quality-adjusted life years (QALYs). DISCUSSION: The DIVERTI 2 trial is a prospective, multicenter, randomized, study to define the best strategy between PS and no PS in resection and primary anastomosis for patients presenting with peritonitis due to perforated diverticulitis. TRIAL REGISTRATION: ClinicalTrial.gov: NCT04604730 date of registration October 27, 2020. https://clinicaltrials.gov/ct2/show/NCT04604730?recrs=a&cond=Diverticulitis&draw=2&rank=12 .