Outcomes of bariatric surgery in patients with inflammatory bowel disease from a French nationwide database.

BACKGROUND: The outcomes of bariatric surgery (BS) in patients with chronic inflammatory bowel disease (IBD) remain rarely described. We aimed to evaluate the 90-day morbidity and mortality rates, and the risk of IBD complications 2 years after BS. METHOD: Patients from the French Programme de Médicalisation des Systèmes d'Information (PMSI) database who underwent a primary BS between 2016 and 2018 were included. We identified patients with a previous diagnosis of IBD. Postoperative 90-day (POD90) morbidity and mortality rates were compared between the two groups. The evolution of IBD was followed 2 years after BS. RESULTS: Between 2016 and 2018, 138 980 patients underwent primary BS, including 587 patients with IBD: 326 (55.5 per cent) with Crohn's disease (CD) and 261 (44.5 per cent) with ulcerative colitis (UC). The preferred surgical technique was sleeve gastrectomy, especially in the IBD group (81.1 per cent), followed by gastric bypass (14.6 per cent). Patients with IBD had more comorbidities (Charlson Comorbidity Index of 1 or more, hypertension, and diabetes; P < 0.001) than those without IBD. The POD90 mortality rate did not differ between the two groups (0.049 per cent in the IBD group versus 0 per cent in the non-IBD group), but more unscheduled rehospitalizations at POD90 were observed in patients with IBD (6.0 per cent versus 3.7 per cent; P = 0.004). Two years after BS, 86 patients (14.6 per cent) in the IBD group had at least one unplanned readmission for the management of their IBD; 15 patients stayed for 3 or more days. After multivariable analysis, patients with CD had an independent elevated risk of IBD-related unplanned readmissions 2 years after BS versus UC (adjusted odds ratio 1.90, 95 per cent c.i. 1.22 to 2.97; P = 0.005). CONCLUSION: In a highly selected cohort of patients with well-controlled IBD, BS did not result in added mortality or morbidity. A point of vigilance must be underlined regarding BS in patients with CD.

Effect of the Use of Reinforced Stapling on the Occurrence of Pancreatic Fistula After Distal Pancreatectomy: Results of the REPLAY (REinforcement of the Pancreas in distaL pAncreatectomY) Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes. BACKGROUND: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF. METHODS: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out. RESULTS: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P =0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P =0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar. CONCLUSION: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF.

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

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

Hypothermic Oxygenated Perfusion Improves Extended Criteria Donor Liver Graft Function and Reduces Duration of Hospitalization Without Extra Cost: The PERPHO Study.

Few studies have evaluated the efficacy or the cost of hypothermic oxygenated perfusion (HOPE) in the conservation of extended criteria donor (ECD) grafts from donation after brain death (DBD) donors during liver transplantation (LT). We performed a prospective, monocentric study (NCT03376074) designed to evaluate the interest of HOPE for ECD-DBD grafts. For comparison, a control group was selected after propensity score matching among patients who received transplants between 2010 and 2017. Between February and November 2018, the HOPE procedure was used in 25 LTs. Immediately after LT, the median aspartate aminotransferase (AST) level was significantly lower in the HOPE group (724UI versus 1284UI; P = 0.046) as were the alanine aminotransferase (ALT; 392UI versus 720UI; P = 0.01), lactate (2.2 versus 2.7; P = 0.01) There was a significant reduction in intensive care unit stay (3 versus 5 days; P = 0.01) and hospitalization (15 versus 20 days; P = 0.01). The incidence of early allograft dysfunction (EAD; 28% versus 42%; P = 0.22) was similar . A level of AST or ALT in perfusate >800UI was found to be highly predictive of EAD occurrence (areas under the curve, 0.92 and 0.91, respectively). The 12-month graft (88% versus 89.5%; P = 1.00) and patient survival rates (91% versus 91.3%; P = 1.00) were similar. The additional cost of HOPE was estimated at € 5298 per patient. The difference between costs and revenues, from the hospital's perspective, was not different between the HOPE and control groups (respectively, € 3023 versus € 4059]; IC, -€ 5470 and € 8652). HOPE may improve ECD graft function and reduce hospitalization stay without extra cost. These results must be confirmed in a randomized trial.

Is systematic nasogastric decompression after pancreaticoduodenectomy really necessary?

BACKGROUND: Since the spread of enhanced recovery programs, early withdrawal of the nasogastric tube (NGT) is recommended after pancreaticoduodenectomy (PD), although few data on the safety of this practice are available. The aim of the present study was to evaluate the absence of nasogastric decompression after PD on postoperative outcome. STUDY DESIGN: All consecutive patients undergoing PD between January 2014 and December 2015 at a single center were retrospectively analyzed. Since May 2015, all operated patients had the NGT removed immediately after the procedure (NGT- group) and were compared to patients operated before this practice (NGT+ group), who had the NGT maintained until at least postoperative day 3. RESULTS: During the study period, 139 patients underwent PD, of whom 40 (29%) were in the NGT- group and 99 (71%) were in the NGT+ group. The length of hospital stay (LOS) and rate of postoperative complications of grade 2 or higher according to the Clavien-Dindo grading system were significantly higher in the NGT+ group [14 (11-25) vs. 10 (8-14.2), P = 0.005 and 82.8 vs. 40%, P < 0.001, respectively]. Incidence and severity of delayed gastric emptying (DGE) grade B-C were also higher in the NGT+ group (45.5 vs. 7.5%, P < 0.001). There was no difference between the two groups concerning the 90-day postoperative mortality (P = 0.18). CONCLUSION: The absence of systematic nasogastric decompression after PD might reduce postoperative complications, DGE, and LOS. These encouraging results deserve to be confirmed by a prospective randomized study (NCT: 02594956).

Preoperative bevacizumab and surgery for colorectal liver metastases: a propensity score analysis.

PURPOSE: Bevacizumab associated with conventional chemotherapy has become standard care in the management of metastatic colorectal cancer. However, its impact on outcomes after liver resections (LRs) remains debated. The aim of this study was to evaluate the impact of neoadjuvant bevacizumab-based chemotherapy (BBC) on postoperative outcomes of LR for colorectal liver metastasis (CLM) using a validated approach. METHODS: All patients who received neoadjuvant therapy for CLMs between January 2005 and May 2011 were included. Risk factors for major complications (Clavien ≥3) were analyzed by univariate and multivariate analysis. Evaluation of BBC's impact on morbidity was conducted after a propensity score adjustment on factors identified to influence major complications (MCs). RESULTS: LR for CLMs after neoadjuvant chemotherapy was performed in 199 patients (127 men and 72 women). Major LR was performed on 111 patients (55.78%), and MCs occurred in 41 cases (20.6%). After multivariate analyses, major LR (OR 2.85; 95% CI 1.29-6.85; P = 0.013) and combined resections of both the primary tumor and CLMs (OR 7.12; 95% CI: 2.6-20.5; P < 0.001) were independent predictive factors for MCs. After a propensity score matching, 56 patients with a BBC regimen were compared to 112 patients without BBC. No difference in terms of biliary fistula occurrence (P = 0.94) or 90-day mortality (P = 0.66) was found. Both in the univariate and multivariate analyses, BBC was not associated with MCs (P = 0.95). CONCLUSION: The present study using propensity score matching demonstrated that BBC did not impair outcomes of LR for CLM.

Impact of stroma LOXL2 overexpression on the prognosis of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis related to early recurrence especially in the remnant liver after surgery. ICC exhibits a dense desmoplastic stroma which plays a pivotal role in ICC aggressiveness. Thus, analyzing gene deregulation in the stroma of ICC may help to identify new prognosis biomarkers and promising therapeutic targets. The aim of this study was to evaluate the clinical relevance of the matrix-remodeling enzyme lysyl oxidase-like 2 (LOXL2) expression in ICC. MATERIAL AND METHODS: LOXL2 messenger RNA levels were evaluated in microdissected tumoral stroma (TS) and in nontumoral fibrous tissue by gene expression profiling (testing set, n = 10) obtained from gene expression omnibus database and by quantitative real time polymerase chain reaction (validating set, n = 6). LOXL2 protein levels were evaluated by immunohistochemistry on a tissue microarray containing 80 independent patients. The relationship between LOXL2 expression and survival was assessed by univariate and multivariate analyses. RESULTS: LOXL2 messenger RNA levels were increased in TS, both in the testing and the validating sets (P < 0.01). These results were confirmed at a protein level, with a significantly higher LOXL2 immunostaining in TS (P < 0.01). Univariate analysis revealed that LOXL2 expression was correlated with a poor overall survival and disease-free survival (P < 0.01). Importantly, high expression of LOXL2 was an independent prognostic factor of worst overall survival (hazard ratio = 5.29, confidence interval [CI] 95% = 1.71-16.3, P < 0.01) and disease-free survival (hazard ratio = 5.55, CI 95% = 2.14-14.37, P < 0.01). CONCLUSIONS: Our study provides additional arguments for a role of extracellular matrix remodeling in ICC aggressiveness and identifies LOXL2 as a new prognostic marker and a promising therapeutic target in ICC.

The true prognosis of resected distal cholangiocarcinoma.

BACKGROUND: Prognosis of distal cholangiocarcinoma (DCC) after pancreaticoduodenectomy (PD) remains poorly assessed. The aims of this study were to describe the oncological results of PD in DCC and to compare its prognosis to pancreatic ductal adenocarcinoma (PDAC). METHODS: All PD for periampullary carcinoma performed between January 2000 and March 2013 were extracted from a prospective database. Risk factors likely to influence overall (OS) and disease-free (DFS) survivals of DCC were assessed by multivariable analyses. The DCC and PDAC prognoses were compared after matching using propensity score (nearest neighbor matching). RESULTS: Of the 290 patients analyzed, 56 had DCC, with a mean age of 65 ± 15 years. The median OS was 36.9 months. Recurrence occurred in 35 patients (67%), mostly in the liver (37%). The median DFS was 14.6 months. Combined organ resection was an independent risk factor for worse OS and DFS (P = 0.01 and P = 0.001, respectively). Matching analysis found no significant difference between DCC and PDAC in terms of OS (P = 0.284) or DFS (P = 0.438). CONCLUSION: This first propensity analysis demonstrated that DCC and PDAC have the same prognosis, linked to the high rate of early recurrence, particularly associated with the need for combined organ resection. J. Surg. Oncol. 2016;113:575-580. © 2016 Wiley Periodicals, Inc.

Pancreatic head cancer in patients with chronic pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) is a risk factor of pancreatic adenocarcinoma (PA). The discovery of a pancreatic head lesion in CP frequently leads to a pancreaticoduodenectomy (PD) which preceded by a multidisciplinary meeting (MM). The aim of this study was to evaluate the relevance between this indication of PD and the definitive pathological results. METHODS: Between 2000 and 2010, all patients with CP who underwent PD for suspicion of PA without any histological proof were retrospectively analyzed. The operative decision has always been made at an MM. The definitive pathological finding was retrospectively confronted with the decision made at an MM, and patients were classified in two groups according to this concordance (group 1) or not (group 2). Clinical and biological parameters were analyzed, preoperative imaging were reread, and confronted to pathological findings in order to identify predictive factors of malignant degeneration. RESULTS: During the study period, five of 18 (group 1) patients with CP had PD were histologically confirmed to have PA, and the other 13 (group 2) did not have PA. The median age was 52.5+/-8.2 years (gender ratio 3.5). The main symptoms were pain (94.4%) and weight loss (72.2%). There was no patient's death. Six (33.3%) patients had a major complication (Clavien-Dindo classification ≥ 3). There was no statistical difference in clinical and biological parameters between the two groups. The rereading of imaging data could not detect efficiently all patients with PA. CONCLUSIONS: Our results confirmed the difficulty in detecting malignant transformation in patients with CP before surgery and therefore an elevated rate of unnecessary PD was found. A uniform imaging protocol is necessary to avoid PD as a less invasive treatment could be proposed.

Does an aberrant right hepatic artery really influence the short- and long-term results of a pancreaticoduodenectomy for malignant disease? A matched case-controlled study.

BACKGROUND: An aberrant right hepatic artery (ARHA) is a common anatomic variation. The risk associated with ARHA during pancreaticoduodenectomy (PD) continues to be debated. The aim of this study was to compare the clinical outcomes and survival after PD with ARHA against a matched cohort of patients without ARHA. METHODS: PD with an ARHA performed between January 2000 and September 2009 were retrospectively analyzed. Patients with an ARHA (group 1) were matched (1:2) to patients without an ARHA (group 2) according to gender, age, body mass index, type of tumor, and lymph node status. Peri- and postoperative outcomes were compared between the two groups. Overall survival and disease-free survival were estimated by Kaplan-Meier method and compared with log-rank test. RESULTS: A total of 29 patients (group 1) and 55 patients (group 2) were compared. In group 1, an ARHA entered the tumor in six cases (20.7%), was sacrificed in four cases, and repaired in two cases. There was no difference regarding the rate of intraoperative and postoperative variables between the two groups. The oncological clearance (P = 0.731) and survival (overall survival, P = 0.843; disease-free survival, P = 0.832) were also similar. CONCLUSIONS: Our study showed that the presence of an ARHA during PD was not associated with worse postoperative outcomes or survival.

Impact of age over 75 years on outcomes after pancreaticoduodenectomy.

BACKGROUND: The risks associated with pancreaticoduodenectomy (PD) in elderly patients continue to be debated. The aim of our study was to assess the incidence of death and postoperative complications following PD and identify the risk factors in patients >75 y. STUDY DESIGN: All patients who underwent PD between January 2000 and September 2009 were analyzed retrospectively. Patients were divided into two groups according to age (Group 1: patients aged <75 y, and Group 2: patients aged ≥ 75 y). Morbidity and perioperative mortality risk factors were analyzed using univariate and multivariate analyses. RESULTS: Among the 314 patients, 273 were included in Group 1 (sex ratio 1.4) and 41 in Group 2 (sex ratio 1). In multivariate analysis, postoperative hemorrhage (PH) (OR 6.61, IC95% [1.96; 22.31], P = 0.002) and age >75 y proved to be predictive factors for mortality (OR 11.04, IC95% [2.57; 47.49], P = 0.001). When compared with Group 1, Group 2 was associated with increased postoperative deaths (24.4% versus 3.66%, P < 0.001) and pancreatic fistulas (26.8% versus 13.2%, P = 0.041), in particular, Grade C fistulas (14.6% versus 4.4%, P = 0.023). In multivariate analysis, only PH proved to be an independent predictive factor for mortality (OR 12.9, IC95% [1.07; 155.5], P = 0.04). CONCLUSIONS: PD in elderly patients aged over 75 y appears to be associated with an increased risk of postoperative death and pancreatic fistula. No single preoperative factor made it possible to predict this risk.

Comparison of alternative arterial anastomosis site during liver transplantation when the recipient's hepatic artery is unusable.

Background: Few studies have analyzed outcomes of liver transplantation (LT) when the recipient hepatic artery (HA) was not usable. Methods: We retrospectively evaluated the outcomes of LT performed using the different alternative sites to HA. Results: Between 2002 and 2017, 1,677 LT were performed in our institution among which 141 (8.4%) with unusable recipient HA were analyzed. Four groups were defined according to the site of anastomosis: the splenic artery (SA group, n=26), coeliac trunk (CT group, n=12), aorta using or not the donor's vessel (Ao group, n=91) and aorta using a vascular prosthesis (Ao-P group, n=12) as conduit. The median number of intraoperative red blood cell transfusions was significantly increased in the Ao and Ao-P groups (5, 5, 8.5 and 16 for SA, CT, Ao and Ao-P group respectively, P=0.002), as well as fresh frozen plasma (4.5, 2.5, 10, 17 for the SA, CT, Ao and Ao-P groups respectively, P=0.001). Hospitalization duration was also significantly increased in the Ao and Ao-P groups (15, 16, 24, 26.5 days for the SA, CT, Ao and Ao-P groups respectively, P<0.001). The occurrence of early allograft dysfunction (EAD) (P=0.07) or arterial complications (P=0.26) was not statistically different. Level of factor V, INR, bilirubin and creatinine during the 7th postoperative days (POD) was significantly improved in the SA group. No difference was observed regarding graft (P=0.18) and patient (P=0.16) survival. Conclusions: In case of unusable HA, intraoperative and postoperative outcomes are improved when using the SA or CT compared to aorta.

Nasogastric Decompression vs No Decompression After Pancreaticoduodenectomy: The Randomized Clinical IPOD Trial.

Importance: Although standardization of pancreaticoduodenectomy (PD) has improved postoperative outcomes, morbidity remains high. Fast-track surgery programs appear to improve morbidity, and avoiding nasogastric tube decompression (NGTD), already outdated in most major abdominal surgery, is strongly suggested after PD by fast-track surgery programs but lacks high-level evidence, especially regarding safety. Objective: To assess in a randomized clinical trial whether the absence of systematic NGTD after PD reduces postoperative complications. Design, Setting, and Participants: The IPOD study (Impact of the Absence of Nasogastric Decompression After Pancreaticoduodenectomy) was an open-label, prospective, single-center, randomized clinical trial conducted at a high-volume pancreatic surgery university hospital in France. In total, 155 patients who were 18 to 75 years of age and required PD for benign or malignant disease were screened for study eligibility. Key exclusion criteria were previous gastric or esophageal surgery and severe comorbidities. Patients were randomly assigned (1:1) to systematic NGTD or to no nasogastric decompression and were followed up until 90 days after surgery. Interventions: For patients without NGTD, the NGT was removed immediately after surgery, whereas for patients with NGTD, the NGT was removed 3 to 5 days after surgery. Main Outcomes and Measures: The primary end point was the occurrence of postoperative complications grade II or higher using the Clavien-Dindo classification. The primary end point and safety were evaluated in the intent-to-treat population. Results: From January 2016 to August 2018, 125 screened patients were considered eligible for the study, and 111 were randomized to no NGTD (n = 52) or to NGTD (n = 59). No patient was lost to follow-up. The 2 groups had similar patient demographic and clinical characteristics at baseline. The median (interquartile range) age was 63.0 (57.0-66.5) years in the group with NGTD (38 [64.4%] were males) and 64.0 (58.0-68.0) years in the group without NGTD (31 [59.6%] were males). The postoperative complication rates grade II or higher were similar between the 2 groups (risk ratio, 0.99; 95% CI, 0.66-1.47; P > .99). Pulmonary complication rates (risk ratio, 0.59; 95% CI, 0.18-1.95; P = .44) and delayed gastric emptying rates (risk ratio, 1.07; 95% CI, 0.52-2.21; P > .99) were not significantly different between the groups. Median (interquartile) length of hospital stay for patients without NGTD was not significantly different compared with those with NGTD (10.0 [9.0-16.3] vs 12.0 [10.0-16.0] days; P = .14). Conclusions and Relevance: The present study found no significant difference in postoperative complication occurrence of Clavien-Dindo classification grade II or higher between systematic NGTD and no NGTD after PD, suggesting that avoiding systematic nasogastric decompression is safe for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02594956.

Expression of long non-coding RNA ANRIL predicts a poor prognosis in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide associated with an increased incidence, limited therapeutic options and absence of reliable prognostic biomarkers. Long non-coding RNAs (lncRNA) emerge as relevant biomarkers in cancer being associated with tumor progression. However, lncRNA have been poorly investigated in iCCA. AIM: To identify lncRNA significantly associated with the survival of patients with iCCA after tumor resection for curative intent. METHODS: Gene expression profiling and Q-RT-PCR were performed from a cohort of 39 clinically well-annotated iCCA. Univariate Cox proportional hazards model with Wald Statistic was used to identify lncRNA significantly associated with overall (OS) and/or disease-free (DFS) survival. RESULTS: A signature made of 9 lncRNA was identified to be significantly (P < 0.05) associated with OS and DFS, including 4 lncRNA (lnc-CDK9-1, XLOC_l2_009441, CDKN2B-AS1, HOXC13-AS) highly expressed in poor prognosis iCCA and 5 lncRNA (lnc-CCHCR1-1, lnc-AF131215.3.1, lnc-CBLB-5, COL18A1-AS2, lnc-RELL2-1) highly expressed in better prognosis iCCA. We further validated CDKN2B-AS1 (ANRIL) as a poor prognosis biomarker, not only in iCCA, but also in hepatocellular carcinoma, kidney renal clear cell carcinoma and uterine corpus endometrial carcinoma. CONCLUSIONS: We report a prognosis lncRNA signature in iCCA and the clinical relevance of CDKN2B-AS1 (ANRIL) overexpression in several cancers.

Pancreatico-jejunostomy decreases post-operative pancreatic fistula incidence and severity after central pancreatectomy.

BACKGROUNDS: Central pancreatectomy (CP) is an alternative to pancreaticoduodenectomy and distal pancreatectomy in benign tumours of pancreatic isthmus management. It is known for a high post-operative pancreatic fistula (POPF) rate. The purpose of this study was to compare POPF incidence between pancreatico-jejunostomy (PJ) and pancreatico-gastrostomy (PG). METHODS: Fifty-eight patients (mean age 53.9 ± 1.9 years) who underwent a CP in four French University Hospitals from 1988 to 2011 were analysed. The distal pancreatic remnant was either anastomosed to the stomach (44.8%, n = 25) or to a Roux-en-Y jejunal loop (55.2%, n = 35) with routine external drainage allowing a systematic search for POPF. POPF severity was classified according to the International Study Group on Pancreatic Fistula (ISGPF) and Clavien-Dindo classifications. RESULTS: The groups were similar on sex ratio, mean age, ASA score, pancreas texture, operative time and operative blood loss. Mean follow-up was 36.2 ± 3.9 months. POPF were significantly more frequent after PG (76.9 versus 37.5%, P = 0.003). PG was associated with significantly higher grade of POPF both when graded with ISGPF classification (P = 0.012) and Clavien-Dindo classification (P = 0.044). There was no significant difference in post-operative bleeding (0.918) and delayed gastric emptying (0.877) between the two groups. Hospital length of stay was increased after PG (23.6 ± 3.5 days versus 16.5 ± 1.9 days, P = 0.071). There was no significant difference in incidence of long-term exocrine (3.8 versus 19.2%, P = 0.134) and endocrine (7.7 versus 9.4%, P = 0.575) pancreatic insufficiencies. CONCLUSION: PG was associated with a significantly higher POPF incidence and severity in CP. We recommend performing PJ especially in older patients to improve CP outcomes.

A novel transforming growth factor beta-induced long noncoding RNA promotes an inflammatory microenvironment in human intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a deadly liver primary cancer associated with poor prognosis and limited therapeutic opportunities. Active transforming growth factor beta (TGFß) signaling is a hallmark of the iCCA microenvironment. However, the impact of TGFß on the transcriptome of iCCA tumor cells has been poorly investigated. Here, we have identified a specific TGFß signature of genes commonly deregulated in iCCA cell lines, namely HuCCT1 and Huh28. Novel coding and noncoding TGFß targets were identified, including a TGFß-induced long noncoding RNA (TLINC), formerly known as cancer susceptibility candidate 15 (CASC15). TLINC is a general target induced by TGFß in hepatic and nonhepatic cell types. In iCCA cell lines, the expression of a long and short TLINC isoform was associated with an epithelial or mesenchymal phenotype, respectively. Both isoforms were detected in the nucleus and cytoplasm. The long isoform of TLINC was associated with a migratory phenotype in iCCA cell lines and with the induction of proinflammatory cytokines, including interleukin 8, both in vitro and in resected human iCCA. TLINC was also identified as a tumor marker expressed in both epithelial and stroma cells. In nontumor livers, TLINC was only expressed in specific portal areas with signs of ductular reaction and inflammation. Finally, we provide experimental evidence of circular isoforms of TLINC, both in iCCA cells treated with TGFß and in resected human iCCA. Conclusion: We identify a novel TGFß-induced long noncoding RNA up-regulated in human iCCA and associated with an inflammatory microenvironment. (Hepatology Communications 2018;2:254-269).