Somatostatin vs. Octreotide for Prevention of Postoperative Pancreatic Fistula The PREFIPS Randomized Clinical Trial A FRENCH 007 - ACHBT Study.

OBJECTIVE: Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment. PATIENTS AND METHODS: Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 µg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs. DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis. RESULTS: Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a non-dilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 d). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (Chi-2 test, P=0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis. CONCLUSIONS: Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy.

Augmented Reality Guided Laparoscopic Liver Resection: A Phantom Study With Intraparenchymal Tumors.

INTRODUCTION: Augmented reality (AR) in laparoscopic liver resection (LLR) can improve intrahepatic navigation by creating a virtual liver transparency. Our team has recently developed Hepataug, an AR software that projects the invisible intrahepatic tumors onto the laparoscopic images and allows the surgeon to localize them precisely. However, the accuracy of registration according to the location and size of the tumors, as well as the influence of the projection axis, have never been measured. The aim of this work was to measure the three-dimensional (3D) tumor prediction error of Hepataug. METHODS: Eight 3D virtual livers were created from the computed tomography scan of a healthy human liver. Reference markers with known coordinates were virtually placed on the anterior surface. The virtual livers were then deformed and 3D printed, forming 3D liver phantoms. After placing each 3D phantom inside a pelvitrainer, registration allowed Hepataug to project virtual tumors along two axes: the laparoscope axis and the operator port axis. The surgeons had to point the center of eight virtual tumors per liver with a pointing tool whose coordinates were precisely calculated. RESULTS: We obtained 128 pointing experiments. The average pointing error was 29.4 ± 17.1 mm and 9.2 ± 5.1 mm for the laparoscope and operator port axes respectively (P = 0.001). The pointing errors tended to increase with tumor depth (correlation coefficients greater than 0.5 with P < 0.001). There was no significant dependency of the pointing error on the tumor size for both projection axes. CONCLUSIONS: Tumor visualization by projection toward the operating port improves the accuracy of AR guidance and partially solves the problem of the two-dimensional visual interface of monocular laparoscopy. Despite a lower precision of AR for tumors located in the posterior part of the liver, it could allow the surgeons to access these lesions without completely mobilizing the liver, hence decreasing the surgical trauma.

Comparing indications, complexity and outcomes of laparoscopic liver resection between centers with and without a liver transplant program: a French nationwide study.

BACKGROUND: There are no data to evaluate the difference in populations and impact of centers with liver transplant programs in performing laparoscopic liver resection (LLR). METHODS: This was a multicenter study including patients undergoing LLR for benign and malignant tumors at 27 French centers from 1996 to 2018. The main outcomes were postoperative severe morbidity and mortality. RESULTS: A total of 3154 patients were included, and 14 centers were classified as transplant centers (N = 2167 patients, 68.7 %). The transplant centers performed more difficult LLRs and more resections for hepatocellular carcinoma (HCC) in patients who more frequently had cirrhosis. A higher rate of performing the Pringle maneuver, a lower rate of blood loss and a higher rate of open conversion (all p < 0.05) were observed in the transplant centers. There was no association between the presence of a liver transplant program and either postoperative severe morbidity (<10 % in each group; p = 0.228) or mortality (1 % in each group; p = 0.915). CONCLUSIONS: Most HCCs, difficult LLRs, and cirrhotic patients are treated in transplant centers. We show that all centers can achieve comparable safety and quality of care in LLR independent of the presence of a liver transplant program.

Pancreatoduodenectomy Following Preoperative Biliary Drainage Using Endoscopic Ultrasound-Guided Choledochoduodenostomy Versus a Transpapillary Stent: A Multicenter Comparative Cohort Study of the ACHBT-FRENCH-SFED Intergroup.

BACKGROUND: It is unclear whether preoperative biliary drainage (PBD) by endoscopic retrograde cholangiopancreatography (ERCP) is equivalent to electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) before pancreatoduodenectomy (PD). METHODS: Patients who underwent PBD for distal malignant biliary obstruction (DMBO) followed by PD were retrospectively included in nine expert centers between 2015 and 2022. ERCP or endoscopic ultrasound-guided choledochoduodenostomy with ECE-LAMS were performed. In intent-to-treat analysis, patients drained with ECE-LAMS were considered the study group (first-LAMS group) and those drained with conventional transpapillary stent the control group (first-cannulation group). The rates of technical success, clinical success, drainage-related complications, surgical complications, and oncological outcomes were analyzed. RESULTS: Among 156 patients, 128 underwent ERCP and 28 ECE-LAMS in first intent. The technical and clinical success rates were 83.5% and 70.2% in the first-cannulation group versus 100% and 89.3% in the first-LAMS group (p = 0.02 and p = 0.05, respectively). The overall complication rate over the entire patient journey was 93.7% in first-cannulation group versus 92.0% in first-LAMS group (p = 0.04). The overall endoscopic complication rate was 30.5% in first-cannulation group versus 17.9% in first-LAMS group (p = 0.25). The overall complication rate after PD was higher in the first-cannulation group than in the first-LAMS group (92.2% versus 75.0%, p = 0.016). Overall survival and progression-free survival did not differ between the groups. CONCLUSIONS: PBD with ECE-LAMS is easier to deploy and more efficient than ERCP in patients with DMBO. It is associated with less surgical complications after pancreatoduodenectomy without compromising the oncological outcome.

Augmented reality in laparoscopic liver resection evaluated on an ex-vivo animal model with pseudo-tumours.

BACKGROUND: The aim of this study was to assess the performance of our augmented reality (AR) software (Hepataug) during laparoscopic resection of liver tumours and compare it to standard ultrasonography (US). MATERIALS AND METHODS: Ninety pseudo-tumours ranging from 10 to 20 mm were created in sheep cadaveric livers by injection of alginate. CT-scans were then performed and 3D models reconstructed using a medical image segmentation software (MITK). The livers were placed in a pelvi-trainer on an inclined plane, approximately perpendicular to the laparoscope. The aim was to obtain free resection margins, as close as possible to 1 cm. Laparoscopic resection was performed using US alone (n = 30, US group), AR alone (n = 30, AR group) and both US and AR (n = 30, ARUS group). R0 resection, maximal margins, minimal margins and mean margins were assessed after histopathologic examination, adjusted to the tumour depth and to a liver zone-wise difficulty level. RESULTS: The minimal margins were not different between the three groups (8.8, 8.0 and 6.9 mm in the US, AR and ARUS groups, respectively). The maximal margins were larger in the US group compared to the AR and ARUS groups after adjustment on depth and zone difficulty (21 vs. 18 mm, p = 0.001 and 21 vs. 19.5 mm, p = 0.037, respectively). The mean margins, which reflect the variability of the measurements, were larger in the US group than in the ARUS group after adjustment on depth and zone difficulty (15.2 vs. 12.8 mm, p < 0.001). When considering only the most difficult zone (difficulty 3), there were more R1/R2 resections in the US group than in the AR + ARUS group (50% vs. 21%, p = 0.019). CONCLUSION: Laparoscopic liver resection using AR seems to provide more accurate resection margins with less variability than the gold standard US navigation, particularly in difficult to access liver zones with deep tumours.

Liver Venous Deprivation or Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy?: A Retrospective Multicentric Study.

OBJECTIVE: To compare 2 techniques of remnant liver hypertrophy in candidates for extended hepatectomy: radiological simultaneous portal vein embolization and hepatic vein embolization (HVE); namely LVD, and ALPPS. BACKGROUND: Recent advances in chemotherapy and surgical techniques have widened indications for extended hepatectomy, before which remnant liver augmentation is mandatory. ALPPS and LVD typically show higher hypertrophy rates than portal vein embolization, but their respective places in patient management remain unclear. METHODS: All consecutive ALPPS and LVD procedures performed in 8 French centers between 2011 and 2020 were included. The main endpoint was the successful resection rate (resection rate without 90-day mortality) analyzed according to an intention-to-treat principle. Secondary endpoints were hypertrophy rates, intra and postoperative outcomes. RESULTS: Among 209 patients, 124 had LVD 37 [13,1015] days before surgery, whereas 85 underwent ALPPS with an inter-stages period of 10 [6, 69] days. ALPPS was mostly-performed for colorectal liver metastases (CRLM), LVD for CRLM and perihilar cholangiocarcinoma. Hypertrophy was faster for ALPPS. Successful resection rates were 72.6% for LVD ± rescue ALPPS (n = 6) versus 90.6% for ALPPS (P < 0.001). Operative duration, blood losses and length-of-stay were lower for LVD, whereas 90-day major complications and mortality were comparable. Results were globally unchanged for CRLM patients, or after excluding the early 2 years of experience (learning-curve effect). CONCLUSIONS: This study is the first 1 comparing LVD versus ALPPS in the largest cohort so far. Despite its retrospective design, it yields original results that may serve as the basis for a prospective study.

Pancreaticoduodenectomy following endoscopic ultrasound-guided choledochoduodenostomy with electrocautery-enhanced lumen-apposing stents an ACHBT - SFED study.

BACKGROUND: After ERCP failure or if ERCP is declined for preoperative biliary drainage before pancreaticoduodenectomy, endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with electrocautery-enhanced lumen-apposing stents (ECE-LAMS) might be needed. The aim of the present study was to assess the technical feasibility and short-term outcomes of pancreaticoduodenectomy (PD) following endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with electrocautery-enhanced lumen-apposing stents (ECE-LAMS). METHODS: A retrospective study of all EUS-CDS procedures with ECE-LAMS followed by PD performed in France since the availability of the device in 2016. RESULTS: 21 patients underwent PD in 9 departments of surgery following EUS-CDS with ECE-LAMS. The median bilirubin level at endoscopic procedure was 292 µmol/L. A 6 mm diameter stent was used in 20 cases. No complications occurred during the procedure. During the waiting time, 1 patient had an acute pancreatitis post ERCP and 3 patients developed cholangitis, treated by either an additional percutaneous biliary drainage, or an endoscopic procedure to extract a bezoar occluding the stent, or antibiotics, respectively. PD with a curative intent was performed in all cases. Overall, postoperative mortality was nil and postoperative morbidity occurred in 17 patients (81%), including 3 with severe complications (14%). No patient developed postoperative biliary fistula. In the 21 patients followed at least 6 months, no biliary complications occurred, and no tumor recurrence developed on the hepaticojejunostomy/hepatic pedicle. CONCLUSION: Pancreaticoduodenectomy following EUS-CDS with ECE-LAMS is technically feasible with acceptable short-term postoperative outcome, including healing of biliary anastomosis.

A case series study of augmented reality in laparoscopic liver resection with a deformable preoperative model.

BACKGROUND: Previous work in augmented reality (AR) guidance in monocular laparoscopic hepatectomy requires the surgeon to manually overlay a rigid preoperative model onto a laparoscopy image. This may be fairly inaccurate because of significant liver deformation. We have proposed a technique which overlays a deformable preoperative model semi-automatically onto a laparoscopic image using a new software called Hepataug. The aim of this study is to show the feasibility of Hepataug to perform AR with a deformable model in laparoscopic hepatectomy. METHODS: We ran Hepataug during the procedures, as well as the usual means of laparoscopic ultrasonography (LUS) and visual inspection of the preoperative CT or MRI. The primary objective was to assess the feasibility of Hepataug, in terms of minimal disruption of the surgical workflow. The secondary objective was to assess the potential benefit of Hepataug, by subjective comparison with LUS. RESULTS: From July 2017 to March 2019, 17 consecutive patients were included in this study. AR was feasible in all procedures, with good correlation with LUS. However, for 2 patients, LUS did not reveal the location of the tumors. Hepataug gave a prediction of the tumor locations, which was confirmed and refined by careful inspection of the preoperative CT or MRI. CONCLUSION: Hepataug showed a minimal disruption of the surgical workflow and can thus be feasibly used in real hepatectomy procedures. Thanks to its new mechanism of semi-automatic deformable alignment, Hepataug also showed a good agreement with LUS and visual CT or MRI inspection in subsurface tumor localization. Importantly, Hepataug yields reproducible results. It is easy to use and could be deployed in any existing operating room. Nevertheless, comparative prospective studies are needed to study its efficacy.

Combined biembolization induces higher hypertrophy than portal vein embolization before major liver resection.

BACKGROUND: Combined preoperative portal and hepatic vein embolization (biembolization, BE) has been recently described and may further enhance preoperative FLR growth. The objective of this study was to compare the efficacy of combined preoperative biembolization and portal vein embolization (PVE). METHODS: This study was performed between 2010 and 2017. From 2010 to 2014, patients only underwent preoperative PVE. After 2014, BE was proposed as an alternative to PVE. Liver volumetry was assessed by a CT-scan before BE or PVE and then three weeks later. RESULTS: During the study period, 72 patients underwent radiological procedures that included 41 PVE (PVE group) and 31 BE (BE group). The time elapsing between the procedure and surgery was similar (p = 0.760). The mean percentage of FLR ratio hypertrophy in the PVE group was 31.9% (±34), but reached 51.2% (±42) in the BE group (p = 0.018) and this difference remained significant under multivariate analysis that included age, gender, body mass index, diabetes mellitus, cirrhosis and NASH. The kinetic growth rates were 19% (±17%) and 8% (±13%) in the BE and PVE groups, respectively (p = 0.026). CONCLUSION: This study shows that BE induces higher hypertrophy than portal vein embolization before major liver resection with no more morbidity.

Preliminary trial of augmented reality performed on a laparoscopic left hepatectomy.

BACKGROUND: Laparoscopic liver surgery is seldom performed, mainly because of the risk of hepatic vein bleeding or incomplete resection of the tumour. This risk may be reduced by means of an augmented reality guidance system (ARGS), which have the potential to aid one in finding the position of intrahepatic tumours and hepatic veins and thus in facilitating the oncological resection and in limiting the risk of operative bleeding. METHODS: We report the case of an 81-year-old man who was diagnosed with a hepatocellular carcinoma after an intraabdominal bleeding. The preoperative CT scan did not show metastases. We describe our preferred approach for laparoscopic left hepatectomy with initial control of the left hepatic vein and preliminary results of our novel ARGS achieved postoperatively. In our ARGS, a 3D virtual anatomical model is created from the abdominal CT scan and manually registered to selected laparoscopic images. For this patient, the virtual model was composed of the segmented left liver, right liver, tumour and median hepatic vein. RESULTS: The patient's operating time was summed up to 205 min where a blood loss of 300 cc was recorded. The postoperative course was simple. Histopathological analysis revealed the presence of a hepatocellular carcinoma with free margins. Our results of intrahepatic visualization suggest that ARGS can be beneficial in detecting the tumour, transection plane and medial hepatic vein prior to parenchymal transection, where it does not work due to the substantial changes to the liver's shape. CONCLUSIONS: As of today, we have performed eight similar left hepatectomies, with good results. Our ARGS has shown promising results and should now be attempted intraoperatively.

Combined Preoperative Portal and Hepatic Vein Embolization (Biembolization) to Improve Liver Regeneration Before Major Liver Resection: A Preliminary Report.

BACKGROUND: Insufficient volume of the future liver remnant (FLR) is a major cause of non-resectable disease in patients presenting with primary or metastatic liver tumours. The objective of this study was to evaluate the safety and efficacy of the combined preoperative portal and hepatic vein embolization (biembolization) before extended right liver resections. METHODS: This retrospective study was performed in a tertiary centre between 2014 and 2015. Combined right portal and hepatic vein embolization (biembolization) was proposed, as an alternative to ALPPS procedure, for all patients with primary or metastatic liver tumour, before right extended hepatectomy. CT scan liver volumetry was assessed before biembolization, three weeks after biembolization and one week after surgery. RESULTS: Seven patients underwent biembolization. All patients had right portal vein embolization (PVE) combined with right hepatic vein embolization (HVE, n = 4), median HVE (n = 2) and right + median HVE (n = 1). Three patients had preoperative liver disease and two received preoperative chemotherapy. No biembolization procedure-related complications occurred. The mean FLR regeneration rate was 52.6% (range: 18.2-187.9) after the biembolization. One patient with gallbladder carcinoma was not operated because of peritoneal carcinomatosis diagnosed after the biembolization. The remnant six patients did not develop postoperative liver failure. CONCLUSIONS: Biembolization seems to induce safe, reproducible and effective FLR growth before extended right hepatectomy, in patients with primary or metastatic liver tumour.

Does intraoperative closed-suction drainage influence the rate of pancreatic fistula after pancreaticoduodenectomy?

BACKGROUND: Although drainage of pancreatic anastomoses after pancreaticoduodenectomy (PD) is still debated, it remains recommended, especially in patients with a high risk of post-operative pancreatic fistula (POPF). Modalities of drainage of pancreatic anastomoses, especially the use of passive (PAD) or closed-suction (CSD) drains, and their impact on surgical outcomes, have been poorly studied. The aim was to compare CSD versus PAD on surgical outcomes after PD. METHODS: Retrospective analysis of 197 consecutive patients who underwent a standardized PD at two tertiary centers between March 2012 and April 2015. Patients with PAD (n = 132) or CSD (n = 65) were compared. RESULTS: There was no significant difference in terms of 30-day overall and severe post-operative morbidity, post-operative hemorrhage, post-operative intra-abdominal fluid collections, 90-day post-operative mortality and mean length of hospital stay. The rate of POPF was significantly increased in the CSD group (47.7% vs. 32.6%; p = 0.04). CSD was associated with an increase of grade A POPF (21.5% vs. 8.3%; p = 0.03), while clinically relevant POPF were not impacted. In patients with grade A POPF, the rate of undrained intra-abdominal fluid collections was increased in the PAD group (46.1% vs. 21.4%; p = 0.18). After multivariate analysis, CSD was an independent factor associated with an increased rate of POPF (OR = 2.43; p = 0.012). CONCLUSIONS: There was no strongly relevant difference in terms of surgical outcomes between PAD or CSD of pancreatic anastomoses after PD, but CSD may help to decrease the rate of undrained post-operative intra-abdominal collections in some patients. Further randomized, multi-institutional studies are needed.

Early Enteral Versus Total Parenteral Nutrition in Patients Undergoing Pancreaticoduodenectomy: A Randomized Multicenter Controlled Trial (Nutri-DPC).

OBJECTIVES: The aim of this study was to compare nasojejunal early enteral nutrition (NJEEN) with total parenteral nutrition (TPN), after pancreaticoduodenectomy (PD), in terms of postoperative complications. BACKGROUND: Current nutritional guidelines recommend the use of enteral over parenteral nutrition in patients undergoing gastrointestinal surgery. However, the NJEEN remains controversial in patients undergoing PD. METHODS: Multicenter, randomized, controlled trial was conducted between 2011 and 2014. Nine centers in France analyzed 204 patients undergoing PD to NJEEN (n = 103) or TPN (n = 101). Primary outcome was the rate of postoperative complications according to Clavien-Dindo classification. Successful NJEEN was defined as insertion of a nasojejunal feeding tube, delivering at least 50% of nutritional needs on PoD 5, and no TPN for more than consecutive 48 hours. RESULTS: Postoperative complications occurred in 77.5% [95% confidence interval (95% CI) 68.1-85.1] patients in the NJEEN group versus 64.4% (95% CI 54.2-73.6) in TPN group (P = 0.040). NJEEN was associated with higher frequency of postoperative pancreatic fistula (POPF) (48.1% vs 27.7%, P = 0.012) and higher severity (grade B/C 29.4% vs 13.9%; P = 0.007). There was no significant difference in the incidence of post-pancreatectomy hemorrhage, delayed gastric emptying, infectious complications, the grade of postoperative complications, and the length of postoperative stay. A successful NJEEN was achieved in 63% patients. In TPN group, average energy intake was significantly higher (P < 0.001) and patients had an earlier recovery of oral feeding (P = 0.0009). CONCLUSIONS: In patients undergoing PD, NJEEN was associated with an increased overall postoperative complications rate. The frequency and the severity of POPF were also significantly increased after NJEEN. In terms of safety and feasibility, NJEEN should not be recommended.

High Resectability Rate of Initially Unresectable Colorectal Liver Metastases After UGT1A1-Adapted High-Dose Irinotecan Combined with LV5FU2 and Cetuximab: A Multicenter Phase II Study (ERBIFORT).

BACKGROUND: The purpose of this study was to assess the efficacy and tolerance of induction chemotherapy combining LV5FU2 with increased doses of irinotecan adapted to UGT1A1 genotyping and cetuximab in untreated potentially resectable liver metastases of colorectal cancer. METHODS: Twenty-six patients, PS 0-1, with class II hepatic metastases received chemotherapy combining irinotecan 260 mg/m(2) on day 1 for UGT1A1 6/6 and 6/7 genotypes and 220 mg/m(2) for UGT1A1 7/7 genotypes, with leucovorin on day 1, 5FU 400 mg/m(2) bolus on day 1 and continuous 5FU infusion for 46 h, and cetuximab on day 1 (day 1 = day 14). Primary prevention with lenograstim (day 5-9) was given to UGT1A1 6/7 and 7/7 genotypes. The primary endpoint was the response rate (RECIST1.1), and the secondary endpoints were tolerance (NCI-CTC criteria) and R0 resection rate. RESULTS: The average number of cycles per patient was 6 (±1.9). The UGT1A1 genotype was 6/6 in 34.6 %, 6/7 in 53.9 %, and 7/7 in 11.5 % of patients. At 6 cycles, 18 patients (69.2 %) presented a partial response, 5 patients (19.2 %) had stable disease, 2 patients (7.7 %) died independently of chemotherapy, and 1 patient (3.9 %) refused the treatment after 3 cycles. Four patients received 2 more cycles and the cumulative response rate at 8 cycles was 76.9 % (20/26). There was no progression. Among assessable patients (n = 23), the overall response rate was 82.6 % and 21 patients (80.7 %) had a metastasis resection. The most frequent grade 3-4 toxicities were neutropenia (31 %), diarrhea (20.8 %), and anorexia (16.4 %). There were no deaths due to toxicity. CONCLUSIONS: High-dose FOLFIRI combined with cetuximab yielded high response rates and enabled complete resection of class II hepatic metastases in most patients. It seemed to be well-tolerated among healthy selected patients thanks to irinotecan dose adaptation according to UGT1A1 pharmacogenomics status. This intensified chemotherapy regimen needs to be confirmed in a randomized, phase III study.

Pancreaticobiliary maljunction and choledochal cysts: from embryogenesis to therapeutics aspects.

Pancreaticobiliary maljunction (PBM) and choledochal cysts (CC) are rare and little-known diseases. Several definitions have been proposed for the PBM, but the most widely accepted is an excessive length of the common pancreaticobiliary duct due to the abnormal convergence of the pancreatic and biliary ducts out of the duodenal wall. This anomaly, thought to develop during embryogenesis, is associated with a loss of regulation of the Oddi's sphincter leading to a pancreaticobiliary or biliopancreatic backflow. This reflux could be responsible, or associated with cystic dilatation of the bile ducts and biliary tract cancers, to various biliary or pancreatic events such as cholangitis or pancreatitis. For the diagnosis of PBM, magnetic resonance cholangiopancreatography has now become the gold standard as a noninvasive imaging tool. However, the main risk of PBM is the development of bile duct cancer, most often on a distended area. PBM without CC increase the occurrence of gallbladder cancer and require a preventive cholecystectomy. Surgical treatment of PBM with concomitant CC is more complex and depends on localization of the dilatation(s) as reported in the Todani's classification. This review describes the pathogenesis, embryogenesis, clinical features, investigation and management of PBM and CC.

Endoscopic ultrasound-guided biliary drainage after failed ERCP: cumulative experience of 101 procedures at a single center.

BACKGROUND AND STUDY AIM: Endoscopic ultrasound (EUS)-guided biliary access is an alternative to percutaneous access after failed endoscopic retrograde cholangiopancreatography (ERCP). This report presents 7 years' cumulative experience of EUS-guided biliary drainage for obstructive jaundice in patients with failed ERCP. PATIENTS AND METHODS: Between February 2006 and February 2013, 101 patients (malignant = 98, benign = 3) with previous failed ERCP underwent an EUS intra- or extrahepatic approach with transluminal stenting or an EUS-guided rendezvous procedure with transpapillary stent placement. A single endoscopist performed all procedures. RESULTS: A total of 71 patients underwent the intrahepatic approach (66 hepatogastrostomies and 5 EUS-guided rendezvous), and 30 underwent the extrahepatic approach (26 choledochoduodenostomies, 1 choledochojejunostomy, 1 choledochoantrostomy, and 2 EUS-guided cholangiographies). Technical and clinical success rates were 98.0 % and 92.1 %, respectively. There was no difference in efficacy between hepatogastrostomies and choledochoduodenostomies (94 % vs. 90 %; P = 0.69) or in major complications (10.6 % vs. 6.7 %; P = 1). Adverse events occurred in 12 patients (11.9 %): 10 in the hepatogastrostomy group (2 limited pneumoperitoneum, 1 hepatic hematoma, 5 bile leakage, 2 sepsis), and 2 in the choledochoduodenostomy group (1 arteriobiliary fistula and 1 sepsis). There were six procedure-related deaths, five among the first 50 patients and one among the last 51 patients. Hepatogastrostomy vs. choledochoduodenostomy, plastic vs. metal stenting, stent-in-stent vs. 1 stent, nasobiliary drain, or postoperative octreotide infusion were not prognostic of bile leakage. CONCLUSION: EUS-guided biliary drainage is an efficient technique, but is associated with significant morbidity that seems to decrease with the learning curve. It should be performed in tertiary care centers in selected patients. Prospective randomized studies are needed to compare EUS-guided biliary drainage with percutaneous transhepatic cholangiography drainage.

Previous radiation for prostate neoplasm alters surgical and oncologic outcomes after rectal cancer surgery.

BACKGROUND: Previous radiation for prostate cancer (PC) contra-indicates neoadjuvant chemoradiotherapy for rectal cancer (RC) because of risk of cumulative radiation dose toxicity. Postoperative outcomes after proctectomy have not been well studied in these patients who did not receive optimal treatment. METHODS: Eighty-four consecutive male patients underwent surgery for stage II-III mid or low RC between 2002 and 2011. Patients who previously received radiation for PC (n = 8) and patients who had not previously undergone radiation for PC but who received neoadjuvant chemoradiotherapy for RC (n = 64) were retrospectively compared. RESULTS: Previous radiation for PC was an independent factor that significantly increased intraoperative (25% vs. 1.6%, P = 0.002) and postoperative morbidities (62.5% vs. 28.1%, P = 0.028), anastomotic leakage (62.5% vs. 12.5%, P < 0.001) and definitive stoma rates (25% vs. 17.4%, P = 0.022). It significantly altered median overall survival (32.0 vs. 130.6 months, P = 0.05) and local recurrence-free survival rates (14.0 months vs. "median not reached," P = 0.016). CONCLUSIONS: This is the first report of altered survival rates after proctectomy in patients who had previously received radiation for PC. Postoperative morbidity and definitive defunctioning stoma rates were significantly increased in these patients with poor prognoses. Therapeutic strategies should thus be individualized. Large, multicenter cohort studies are needed.

Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype.

BACKGROUND: Escherichia coli strains harbouring the pks island (pks+ E. coli) are often seen in human colorectal tumours and have a carcinogenic effect independent of inflammation in an AOM/IL-10(-/-) (azoxymethane/interleukin) mouse model. OBJECTIVE: To investigate the mechanism sustaining pks+ E. coli-induced carcinogenesis. METHOD: Underlying cell processes were investigated in vitro and in vivo (xenograft model) using intestinal epithelial cells infected by pks+ E. coli or by an isogenic mutant defective for pks (pks- E. coli). The results were supported by data obtained from an AOM/DSS (azoxymethane/dextran sodium sulphate) colon cancer mouse model and from human colon cancer biopsy specimens colonised by pks+ E. coli or pks- E. coli. RESULTS: Colibactin-producing E. coli enhanced tumour growth in both xenograft and AOM/DSS models. Growth was sustained by cellular senescence (a direct consequence of small ubiquitin-like modifier (SUMO)-conjugated p53 accumulation), which was accompanied by the production of hepatocyte growth factor (HGF). The underlying mechanisms involve microRNA-20a-5p, which targets SENP1, a key protein regulating p53 deSUMOylation. These results are consistent with the expression of SENP1, microRNA-20a-5p, HGF and phosphorylation of HGF receptor found in human and mouse colon cancers colonised by pks+ E. coli. CONCLUSION: These data reveal a new paradigm for carcinogenesis, in which colibactin-induced senescence has an important role.