Learning curve for robotic-assisted total mesorectal excision: a multicentre, prospective study.

AIM: Robotic-assisted surgery (RAS) is becoming increasingly important in colorectal surgery. Recognition of the short, safe learning curve (LC) could potentially improve implementation. We evaluated the extent and safety of the LC in robotic resection for rectal cancer. METHOD: Consecutive rectal cancer resections (January 2018 to February 2021) were prospectively included from three French centres, involving nine surgeons. LC analyses only included surgeons who had performed more than 25 robotic rectal cancer surgeries. The primary endpoint was operating time LC and the secondary endpoint conversion rate LC. Interphase comparisons included demographic and intraoperative data, operating time, conversion rate, pathological specimen features and postoperative morbidity. RESULTS: In 174 patients (69% men; mean age 62.6 years) the mean operating time was 334.5 ± 92.1 min. Operative procedures included low anterior resection (n = 143) and intersphincteric resection (n = 31). For operating time, there were two or three (centre-dependent) LC phases. After 12-21 cases (learning phase), there was a significant decrease in total operating time (all centres) and an increase in the number of harvested lymph nodes (two centres). For conversion rate, there were two or four LC phases. After 9-14 cases (learning phase), the conversion rate decreased significantly in two centres; in one centre, there was a nonsignificant decrease despite the treatment of significantly more obese patients and patients with previous abdominal surgery. There were no significant differences in interphase comparisons. CONCLUSION: The LC for RAS in rectal cancer was achieved after 12-21 cases for the operating time and 9-14 cases for the conversion rate. RAS for rectal cancer was safe during this time, with no interphase differences in postoperative complications and circumferential resection margin.

Intra-versus extracorporeal anastomosis in laparoscopic right colectomy: a meta-analysis of 3699 patients.

BACKGROUND: Laparoscopic right colectomy (LRC) has become a gold standard. However, a major current concern is still whether anastomosis should be performed extracorporeally or entirely laparoscopically. This meta-analysis assesses and compares peri- and postoperative outcomes of intracorporeal anastomosis (IA) versus extracorporeal anastomosis (EA) in LRC. METHODS: The research used the PubMed, Embase and Cochrane databases for studies comparing IA with EA during LRC. Our main endpoint was parietal abscess. Secondary endpoints were 30-day morbidity, mortality, time to onset of gas and stools, length of stay, number of lymph nodes removed and postoperative incisional hernia rates. The MINORS criteria were used to evaluate the quality of the studies examined. RESULTS: Twenty-four articles comprising 3699 patients, published between 2004 and 2020, were included in this meta-analysis. After sensitivity analysis, IA was associated with a decrease in parietal abscesses (OR 0.526, IC 0.333-0.832, p = 0.006). CONCLUSION: This meta-analysis finds that IA allows a decrease in parietal abscesses and time to first gas and stools, surgical repair and length of stay, with similar overall complications.

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

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

Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in two of eight patients with gemcitabine-refractory PDAC. Patients and methods: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1000 mg/m2 (30-min IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate. Results: There was no statistically significant difference in OS between the two treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81-1.65; P = 0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher in the dasatinib arm. Conclusions: Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.

Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment.

BACKGROUND: While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. PATIENTS AND METHODS: Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients. RESULTS: Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity. CONCLUSION: Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.

Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry.

Between 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The same trend was observed with a total ischemia time (TIT) >12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was 89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (-), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL-1 tends to offer the best graft outcome.

Frequent intragenic rearrangements of DPYD in colorectal tumours.

Dihydropyrimidine dehydrogenase is a crucial enzyme for the degradation of 5-fluorouracil (5FU). DPYD, which encodes dihydropyrimidine dehydrogenase, is prone to acquire genomic rearrangements because of the presence of an intragenic fragile site FRA1E. We evaluated DPYD copy number variations (CNVs) in a prospective series of 242 stage I-III colorectal tumours (including 87 patients receiving 5FU-based treatment). CNVs in one or more exons of DPYD were detected in 27% of tumours (deletions or amplifications of one or more DPYD exons observed in 17% and 10% of cases, respectively). A significant relationship was observed between the DPYD intragenic rearrangement status and dihydropyrimidine dehydrogenase (DPD) mRNA levels (both at the tumour level). The presence of somatic DPYD aberrations was not associated with known prognostic or predictive biomarkers, except for LOH of chromosome 8p. No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer.

Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study.

BACKGROUND: To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours. METHODS: This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH. RESULTS: The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR. CONCLUSIONS: Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy.

Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer.

BACKGROUND: We evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m(2) weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression. RESULTS: Between April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n = 63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% CI, 31.9-57.5) in the gemcitabine arm and 60.9% (95% CI, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus 46.2% among the PSCA-negative subgroup. CONCLUSIONS: This randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma. ClinicalTrials.gov identifier: NCT00902291.

Robotic-assisted right colectomy. Official expert recommendations delivered under the aegis of the French Association of Surgery (AFC).

Twenty-seven experts under the aegis of the French Association of Surgery (AFC) offer this reference system with formalized recommendations concerning the performance of right colectomy by robotic approach (RRC). For RRC, experts suggest patient installation in the so-called "classic" or "suprapubic" setup. For patients undergoing right colectomy for a benign pathology or cancer, RRC provides no significant benefit in terms of intra-operative blood loss, intra-operative complications or conversion rate to laparotomy compared to laparoscopy. At the same time, RRC is associated with significantly longer operating times. Data from the literature are insufficient to define whether the robot facilitates the performance of an intra-abdominal anastomosis, but the robotic approach is more frequently associated with an intra-abdominal anastomosis than the laparoscopic approach. Experts also suggest that RRC offers a benefit in terms of post-operative morbidity compared to right colectomy by laparotomy. No benefit is retained in terms of mortality, duration of hospital stay, histological results, overall survival or disease-free survival in RRC performed for cancer. In addition, RRC should not be performed based on the cost/benefit ratio, since RRC is associated with significantly higher costs than laparoscopy and laparotomy. Future research in the field of RRC should consider the evaluation of patient-targeted parameters such as pain or quality of life and the technical advantages of the robot for complex procedural steps, as well as surgical and oncological results.

[Intra and extra hepatic cholangiocarcinomas radiation therapy]. / Place de la radiothérapie des cholangiocarcinomes intra- et extrahépatiques.

Cholangiocarcinomas are digestive tumors whose incidence remains low and have poor prognosis. The benefits of adjuvant radiochemotherapy and radiotherapy have never been demonstrated in any phase III randomized controlled trial. Chemotherapy with capecitabine 6 months is the standard of care in adjuvant setting. Radiochemotherapy is validated in R1 patients. It is not recommended in neoadjuvant situations given the lack of evidence. Chemotherapy and radiochemotherapy are validated in adjuvant or locally advanced diseases. Stereotactic radiation therapy offers an interesting perspective, at the cost of significant digestive toxicities, requiring evaluation in randomized trials.

[Preoperative intensity-modulated radiotherapy of rectal cancers: Relevance and modalities]. / Radiothérapie avec modulation d'intensité préopératoire des cancers rectaux : intérêt et application.

Preoperative radiotherapy boosted by chemotherapy is a recommended treatment in locally advanced rectal cancers. This treatment is delivered by three dimensional conformal irradiation, which is usually well tolerated but can induce potential toxicity such as rectitis, cystitis and hematologic adverse effects. Intensity-modulated radiotherapy, widely available nowadays, allows optimization of volume covering and sparing of organs at risk such as bladder and bone marrow. This review presents relevant clinical situations and requirements for a beneficial and safe preoperative irradiation of rectal cancers by intensity-modulated technique. This technique is compared to three-dimensional conformal radiotherapy.

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

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

[Laparoscopy during pregnancy: experience of the French university hospital of Clermont-Ferrand]. / Coelioscopie en cours de grossesse: expérience du centre hospitalier universitaire (CHU) de Clermont-Ferrand.

OBJECTIVE: To describe perioperative management and perinatal outcome for patients undergoing laparoscopy during pregnancy. PATIENTS AND METHODS: We conducted a retrospective study of all cases of laparoscopy during pregnancy performed in our university hospital over a period of six years (from February 2000 to February 2006). RESULTS: We observed 34 cases managed from five to 30 weeks of gestation (11 cases of adnexal torsion, ten adnexal masses, eight appendicitis, one cholecystitis, one sigmoid volvulus, one pelvic peritonitis, two heterotopic pregnancies). Open laparoscopy was used in 12 cases. Conversion was required in two cases mainly due to adherences (one borderline lesion at 16 weeks and one tubal cyst torsion at 24 weeks). No maternal complication was observed. One miscarriage occurred at Day 1 (peritonitis, five weeks of gestation) and one patient opted for abortion. No threatened preterm labour occurred after the perioperative course and no neonate required admission in neonatology unit. DISCUSSION AND CONCLUSION: This study illustrates safety and efficacy of laparoscopy in management of surgical diseases in the gravid patient. Emergent indications are the most common, highlighting the need for all physicians to know specific recommendations related to laparoscopy during pregnancy.

[Role of endovascular treatment of symptomatic splanchnic artery stenoses in HIV patients: report of three cases]. / Place du traitement endovasculaire des sténoses symptomatiques d'artères digestives chez les sujets infectés par le VIH: trois cas.

Patients with HIV or AIDS frequently present with GI symptoms, sometimes due to early and diffuse atherosclerosis. We report 3 cases of HIV patients with abdominal pain due to severe splanchnic arterial stenosis. Only one patient presented typical clinical findings of mesenteric ischemic. Endovascular treatment was performed in all three cases. Good clinical outcome was immediate in 2 cases. In the third case, subsequent bowel resection was required due to irreversible ischemic injury in spite of local thrombolysis and endovascular revascularization in a patient presenting with acute severe mesenteric ischemia. In all three cases, vascular patency was demonstrated at follow-up. Mesenteric ischemia is a severe complication requiring early diagnosis in HIV patients, especially those with vascular risk factors, especially since endovascular treatment is a valid therapeutic option.

[Tolerance of hypofractionated stereotactic radiotherapy for hepatic tumours]. / Tolérance de l'irradiation stéréotaxique hypofractionnée des tumeurs hépatiques.

PURPOSE: The purpose of the study was to evaluate the outcomes of stereotactic radiation therapy for primary and secondary liver tumours in Jean-Perrin cancer centre (Clermont-Ferrand, France) in terms of efficacy and safety. MATERIALS AND METHODS: Between December 2013 and June 2016, 25 patients were included. Treatment was performed on a linear accelerator Novalis TX®. The prescription dose was 42 to 60Gy in three to five fractions. Local control at 1 year was evaluated with modified Response Evaluation Criteria in Solid Tumours (mRECIST) and RECIST criteria. Acute and late toxicity were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria. RESULTS: Median follow-up was 10.5 months. Treatment tolerance was good with few side effects grade 3 or above, no acute toxicity and only one late toxicity. We have highlighted that hepatic artery haemorrhage was associated with the presence of a biliary prosthesis in contact with the artery (P=0.006) and in the irradiation field. There was no correlation with the dose delivered to the artery and hepatic artery haemorrhage. CONCLUSION: Stereotactic radiation therapy for liver tumours allows a good local control with few secondary effects. Caution should be exercised when treating patients with biliary prostheses in the vicinity of the target volume because there is a risk of haemorrhage of the hepatic artery in contact with the prosthesis.

[Impact of computed tomography on patient's care in nontraumatic acute abdomen: 90 patients]. / Contribution du scanner à la prise en charge des tableaux abdominaux aigus non traumatiques: étude de 90 patients.

OBJECTIVES: To determine the contribution of computerized tomography (CT) to the management of nontraumatic acute abdomen, to evaluate interobserver agreement and the contribution of CT to cost control, to look for the predictive factors of CT. PATIENTS: and method. Ninety prospectively included patients, admitted for nontraumatic acute abdomen and examined by a surgeon, received CT examination. Diagnosis and treatment 1) envisioned before and 2) defined after CT, and 3) finally retained were compared, and the interobserver agreement was calculated after the second reading. The predictive value of the clinical and biological criteria as well as the radiological criteria characterizing these patients was sought. RESULTS: CT was contributive in 68.9% of cases, with a reliable diagnosis and treatment strategy, defined after CT examination, for 92.2% and 90%, respectively. Interobserver agreement was 93.3%. CT contributed to reducing costs in 15.5% of patients, for an additional cost estimated at 104-139 euros. The positive predictive factors of the CT contribution were age over 70 years, localized symptoms, fever, and high CRP. CONCLUSION: In agreement with the literature, in our study CT appears to be a choice examination to guide patient care in nontraumatic acute abdomen.

Feasibility prospective study of laparoscopic cholecystectomy with suprapubic approach.

BACKGROUND: Since the publication of laparoscopic cholecystectomy (LC) using three ports instead of four, no significant evolution has impacted on our clinical practice in order to improve length of stay, postoperative pain, time of recovery and cosmetic results. Recently, a renewed interest has been observed with the suprapubic approach, called occult scar laparoscopic cholecystectomy (OSLC). The aim of this prospective multicentric study was to evaluate the feasibility of OSLC in 2 French centers. METHODS: From March to September 2014, 60 patients were prospectively included in this study. The operation incisions consisted of an umbilical incision for camera; an incision in the right groin for maneuvers of exposition and a suprapubic incision for instrumental dissection and clipping. Outcome was by operative time, operative complications, hospital length of stay, analgesia required after surgery, and cosmetic outcomes. The Patient Satisfaction Scale and Visual Analog Score (VAS) also were used to evaluate the level of cosmetic result and postoperative pain. RESULTS: No laparoscopy was converted to an open procedure, the mean operative time was 53±20min. No patient had intraoperative bile duct injury or significant bleeding. The mean length of stay was 1.70±0.76 days. Two patients (3%) experienced postoperative complication (1 intra-abdominal abscess treated by antibiotics and 1 subcutaneous seroma of the 11-mm port wound treated successfully by needle aspiration). CONCLUSION: The technique proved to be safe and feasible with no specific complication and without specific instrument. It offers satisfactory postoperative pain level and good cosmetic results.