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BackgroundThe liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach.MethodsPatients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis.ResultsOverall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003).ConclusionIn patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

Background Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking. Methods We used gene expression microarrays, real-time PCR, immunoblot, protein-specific ELISA, and gene reporter constructs encoding the enzyme luciferase to study the response of a panel of cancer cells to sorafenib. Tumour explants prepared from surgical hepatocellular carcinoma (HCC) samples and serum samples obtained from HCC patients receiving sorafenib were also used. Results We observed that genes of the metallothionein-1 (MT1) family are induced in the HCC cell line Huh7 exposed to sorafenib. Sorafenib increased the expression of MT1G mRNA in a panel of human cancer cells, an effect that was not observed with eight other clinically-approved kinase inhibitors. We identified the minimal region of the MT1G promoter that confers inducibility by sorafenib to a 133 base pair region containing an Anti-oxidant Response Element (ARE) and showed the essential role of the transcription factor NRF2 (Nuclear factor erythroid 2-Related Factor 2). We examined the clinical relevance of our findings by analysing the regulation of MT1G in five tumour explants prepared from surgical HCC samples. Finally, we showed that the protein levels of MT1 increase in the serum of some HCC patients receiving sorafenib, and found an association with reduced overall survival. Conclusion These findings indicate that MT1 constitute a biomarker adapted for exploring the impact of sorafenib on the redox metabolism of cancer cells.

BackgroundSpontaneous rupture of hepatocellular carcinoma (HCC) remains a life-threatening complication, with a reported mortality rate of between 16 and 30% and an incidence rate of approximately 3% in Europe. Survival data and risk factors after ruptured HCC are lacking, especially for peritoneal metastasis (PM).ObjectivesThe aims of this study were to evaluate the pattern of recurrence and mortality after hepatectomy for ruptured HCC, and to focus on PM.MethodsWe retrospectively reviewed the files of patients admitted to 14 French surgical centers for spontaneous rupture of HCC between May 2000 and May 2012.ResultsOverall, 135 patients were included in this study. The median disease-free survival and overall survival (OS) rates were 16.1 (11.0–21.1) and 28.7 (26.0–31.5) months, respectively, and the median follow-up period was 29 months. At last follow-up, recurrences were observed in 65.1% of patients (n = 88). The overall rate of PM following ruptured HCC was 12% (n = 16). Surgical management of PM was performed for six patients, with a median OS of 36.6 months. An α-fetoprotein level > 30 ng/mL (p = 0.0009), tumor size at rupture > 70 mm (p = 0.0009), and vascular involvement (p < 0.0001) were found to be independently associated with an increased likelihood of recurrence. No risk factor for PM was observed.ConclusionThis large-cohort French study confirmed that 12% of patients had PM after ruptured HCC. A curative approach may be an option for highly selected patients with exclusive PD because of the survival benefit it could provide.

BackgroundSleeve gastrectomy (SG) has become a frequent bariatric procedure. Single-port sleeve gastrectomy (SPSG) could reduce parietal aggression however its development has been restrained due to fear of a complex procedure leading to increased morbidity and suboptimal sleeve construction. The aim of this study was to compare the short-term outcomes of SPSG versus conventional laparoscopic sleeve gastrectomy (CLSG) with regards to morbidity, weight loss, and co-morbidity resolution.MethodsBetween January 2015 and December 2016, data from all consecutive patients that underwent SPSG and CLSG in two institutions performing exclusively one or the other approach were retrospectively analyzed. Propensity score adjustment was performed on the factors known to influence the choice of approach.ResultsDuring the study period, 1122 patients underwent SG in both institutions (610 SPSG and 512 CLSG). From each group, 314 patients were successfully matched. A 15-min increase in operative time was observed during SPSG (P < 0.001). Postoperative morbidity was similar with a minor increase after SPSG (8.6 vs. 6.7%, P = 0.453). No differences in incisional hernia rates were observed (1.6 (SPSG) vs. 0.3% (CLSG), P = 0.216). Percentage of total weight loss was 31.1% and 28.2% in the CLSG and SPSG 12 months after surgery, respectively (P = 0.321). Co-morbidities resolution 12 months following the procedure was similar.ConclusionsSPSG can be performed safely with similar intraoperative and postoperative morbidity compared to CLSG. Weight loss and co-morbidities resolution at 1 year are equivalent. A 15-min longer operative time was the only negative side of SPSG.

Pancreatic fistula (PF) is one of the most common postoperative complications of pancreatoduodenectomy (PD). A recent International Study Group on Pancreatic Fistula (ISGPF) definition grades the severity of PF according to the clinical impact on the patient's hospital course. Although PF is generally treated conservatively (grade A), some cases may require interventional procedures (grade B) or may be life-threatening and necessitate emergency reoperation (grade C). The aim of the present study was to evaluate the incidence of postoperative grade C PF after PD and to assess the prognosis and risk factors for this life-threatening condition. Between January 2000 and December 2006, 680 consecutive patients underwent PD in 5 digestive surgery departments in the northwest region of France (Lille, Amiens, Rouen, and Caen). PF was defined as drain output of any measurable volume of fluid on or after postoperative day 3 with amylase content greater than 3 times the serum amylase activity (ISGPF guidelines). To identify possible risk factors for grade C PF, we reviewed the records of 111 (16.3%) patients with postoperative PF and compared grade C cases with grade A+B cases. The median age was 59 years (range 22–87). The male-to-female ratio was 1.6:1. Fifty-six (50.4%) PDs were performed via pancreaticogastrostomy and 55 via pancreaticojejunostomy. Overall mortality was 2% (n = 14). Grade C PF was observed in 36 (32%) patients, of whom 17 (47%) had sepsis due to an abdominal collection, 16 (44%) had postoperative bleeding, 10 (27.7%) had bleeding associated with abdominal collection, and 3 (9%) had multi-organ failure due to other causes. Of these 36 patients, 35 (97%) underwent reoperation. The mortality rate in grade C PF patients was 38.8%. The major causes of death were sepsis (n = 6) and recurrent bleeding after reoperation (n = 5). Grade C PF increased the duration of postoperative hospitalization (46 vs 29 days, P < .001). Univariate analysis showed that peroperative soft pancreatic parenchyma, peroperative blood transfusion, and postoperative bleeding were significant risk factors for grade C PF, with P values of .011, .003, and .001, respectively. No risk factors for grade C PF were identified in a multivariate analysis. The sensibility, specificity, positive predictive value, and negative predictive value of the presence of the 3 risk factors for grade C PF were 13.89%, 100%, 100%, and 70.75%, respectively. Sixteen percent of patients had PF after PD. Among them, 30% had grade C PF, with a mortality rate of about 40%. Achievement of a 100% predictive positive value for grade C PF after PD in individuals with 3 discriminant risk factors (peroperative soft pancreatic parenchyma, peroperative transfusion, and postoperative bleeding) is a first step towards the identification of high-risk patients who should be managed differently from other patients with PF during or after PD.

BackgroundDay-case surgery (DCS) has become increasingly popular over recent years, as has laparoscopic liver resection (LLR) for the treatment of benign or malignant liver tumours. The purpose of this prospective study was to demonstrate the feasibility of minor LLR as DCS.MethodsProspective, intention-to-treat, non-randomised study of patients undergoing minor LLR between July 2015 and December 2017. Exclusion criteria were resection by laparotomy, major LLR, difficult locations for minor LLR, history of major abdominal surgery, hepatobiliary procedures without liver parenchyma resection, cirrhosis with Child > A and/or portal hypertension, significant medical history and exclusion criteria for DCS. The primary endpoint was the unplanned overnight admission rate. Secondary endpoints were the reason for exclusion, complication data, criteria for DCS evaluation, satisfaction and compliance with the protocol.ResultsOne hundred sixty-seven patients underwent liver resection during the study period. LLR was performed in 92 patients (55%), as DCS in 23 patients (25%). Reasons for minor LLR were liver metastasis (n = 9), hepatic adenoma (n = 5), hepatocellular carcinoma (n = 4), ciliated hepatic foregut cyst (n = 2) and other benign tumours (n = 3). All day-case minor LLR, except two patients, consisted of single wedge resection, while one patient underwent left lateral sectionectomy. There were four unplanned overnight admissions (17.4%), one unscheduled consultation (4.3%), two hospital readmissions (8.6%) and no major complications/mortality. Compliance with the protocol was 69.5%. Satisfaction rate was 91%.ConclusionIn selected patients, day-case minor LLR is feasible with acceptable complication and readmission rates. Day-case minor LLR can therefore be legitimately proposed in selected patients.

BackgroundFew studies on series comparing sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) after failure of gastric banding (GB) are available. The objective of this study was to compare the short- and medium-term outcomes of SG and RYGB after GB.Materials and methodsBetween January 2006 and December 2017, patients undergoing SG (n = 186) or RYGB (n = 107) for failure of primary GB were included in this two-center study. Propensity-score matching was performed based on preoperative factors with a 2:1 ratio. Primary endpoint was the weight loss at 2 years between the SG and RYGB groups. Secondary endpoints were overall mortality and morbidity, reoperation, correction of comorbidities and the rate of adverse events at 2 years follow-up.ResultsIn our propensity score matching analysis, operative time was significantly less in the SG group (95 min vs. 179 min; p < 0.001). Post-operative complications were lower in the SG group (9.5% vs. 35.4%; p = 0.003). At 2 years follow-up, the mean EWL was similar as same as comorbidities. There was a significant difference in favor of SG concerning the rate of adverse events at 2 years follow-up (p < 0.001).ConclusionRevision of GB by SG or RYGB is feasible, with a higher rate of early post-operative complications for RYGB. Weight loss at 2 years follow-up is similar; however, RYGB appears to result in a higher rate of adverse events than SG.

BackgroundLaparoscopy is nowadays considered as the standard approach for hepatic left lateral sectionectomy (LLS), but its value in the prevention of incisional hernia (IH) has not been demonstrated.MethodsBetween 2012 and 2017, patients undergoing laparoscopic (LLLS) or open LLS (OLLS) in 8 centers were compared. Patients undergoing a simultaneous major abdominal procedure were excluded. The incidence of IH was assessed clinically and morphologically on computed tomography (CT) using inverse probability of treatment weighting (IPTW) and multivariable regression analysis.ResultsAfter IPTW, 84 LLLS were compared to 48 OLLS. Compared to OLLS, LLLS patients had reduced blood loss (100 [IQR: 50–200] ml vs. 150 [IQR: 50–415] ml, p = 0.023) and shorter median hospital stay (5 [IQR: 4–7] days vs. 7 [6–9] days, p < 0.001), but experienced similar rate of postoperative complications (mean comprehensive complication index: 12 ± 19 after OLLS versus 13 ± 20 after LLLS, p = 0.968). Long-term radiological screening was performed with a median follow-up of 27.4 (12.1–44.9) months. There was no difference between the two groups in terms of clinically relevant IH (10.7% [n = 9] after LLLS, 8.3% [n = 4] after OLLS, p = 0.768). The rate of IH detected on computed tomography was lower after LLLS than after OLLS (11.9% [n = 10] versus 29.2% [n = 14], p = 0.013). On multivariable analysis, the laparoscopic approach was the only independent factor influencing the risk of morphological IH (OR = 0.290 [95% CI: 0.094–0.891], p = 0.031). The 2 preferential sites for specimen extraction after LLLS were Pfannenstiel and midline incisions, with rates of IH across the extraction site of 2.3% [n = 1/44] and 23.8% [n = 5/21], respectively (p = 0.011).ConclusionThe laparoscopic approach for LLS decreases the risk of long-term IH as evidenced on morphological examinations, with limited clinical impact. Pfannenstiel’s incision should be preferred to midline incision for specimen extraction after LLLS.

Background Identifying the 30% of adhesive small bowel obstructions (aSBO) for which conservative management will require surgery is essential. The association between the previously described radiological score and failure of the conservative management of aSBO remains to be confirmed in a large prospective multicentric cohort. Our aim was to assess the risk factors of failure of the conservative management of aSBO considering the radiological score. Material and Methods This prospective observational study took place in 15 French centers over 3 months. Consecutive patients experiencing aSBO with no early surgery were included. The six radiological features from the Angers radiological computed tomography (CT) score were noted (beak sign, closed loop, focal or diffuse intraperitoneal liquid, focal or diffuse mesenteric haziness, focal or diffuse mesenteric liquid, and diameter of the most dilated small bowel loop > 40 mm). Results Two hundred and seventy nine patients with aSBO were screened. Sixty patients (21.5%) underwent early surgery, and 219 (78.5%) had primary conservative management. In the end, 218 patients were included in the analysis of the risk factors for conservative treatment failure. Among them, 162 (74.3%) had had successful management while for 56 (25.7%) management had failed. In multivariate analysis, a history of surgery was not a significant risk factor for the failure of conservative treatment (OR = 0.11; 95%CI = 0–1.23). A previous episode of aSBO was protective against the failure of conservative treatment (OR = 0.36; 95%CI = 0.15–0.85) and an Angers CT score ≥ 5 as the only individual risk factor (OR = 2.39; 95%CI = 1.01–5.69). Conclusion The radiological score of aSBO is a promising tool in improving the management of aSBO patients. A first episode of aSBO and/or a radiological score ≥5 should lead physicians to consider early surgical management.

The aim of this study was to determine by univariate and multivariate analyses the factors associated with clinically significant anastomotic leakage (AL) after large bowel resection. From 1990 to 1997 a series of 707 patients underwent colonic or rectal resection (without a stoma). Patients were divided into two groups: those with clinical anastomotic leakage (group 1) and those without it (group 2). AL occurred in 43 of 707 patients (6%). The overall mortality was 2.2% and was significantly higher in patients with AL than in those without: 5 of 43 (12%) versus 11 of 664 (1.6%), p <0.001. Univariate analysis showed 15 variables associated with the risk of AL: previous abdominal or pelvic irradiation (p = 0.02), American Society of Anesthesiologists (ASA) score > 2 (p = 0.04), leukocytosis (p = 0.02), renal failure (p = 0.03), steroid treatment (p = 0.01), duration of operation (p = 0.001), intraoperative septic conditions (p = 0.006), total colectomy (p = 0.009), transverse colectomy (p = 0.02), difficulties encountered during anastomosis (p = 0.001), ileorectal anastomosis (p = 0.02), colocolic anastomosis (p = 0.01), abdominal drainage (p = 0.05), and blood transfusion intraoperatively (p = 0.006) and postoperatively (p = 0.001). Multivariate analysis showed that only preoperative leukocytosis (p = 0.04), intraoperative septic conditions (p = 0.001), difficulties encountered during anastomosis (p = 0.007), colocolic anastomosis (p = 0.004), and postoperative blood transfusion (p = 0.0007) were independent factors associated with AL. The risk of AL increased from a range of 12% to 30% if one risk factor was present, to 38% with two factors, to 50% with three factors. After colorectal resection and intraperitoneal anastomosis, a temporary protective stoma is proposed in selected patients with high risk factors for AL, as observed in our study.