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Background: Laparoscopic cholecystectomy is considered nowadays as the standard management of acute cholecystitis (AC). However, results from multicentric studies in the general surgical community are still lacking.Methods: A prospective multicenter survey of surgical management of AC patients was conducted over a 2-year period in Belgium. Operative features and patients' clinical outcome were recorded. The impact of independent predictive factors on the choice of surgical approach, the risk of conversion, and the occurrence of postoperative complications was studied by multivariate logistic regression analysis.Results: Fifty-three surgeons consecutively and anonymously included 1,089 patients in this prospective study. A primary open approach was chosen in 74 patients (6.8%), whereas a laparoscopic approach was the first option in 1,015 patients (93.2%). Independent predictive factors for a primary open approach were previous history of upper abdominal surgery [odds ratio (OR) 4.13, p < 0.001], patient age greater than 70 years (OR 2.41, p < 0.05), surgeon with more than 10 years' experience (OR 2.08, p = 0.005), and gangrenous cholecystitis (OR 1.71, p < 0.05). In the laparoscopy group, 116 patients (11.4%) required conversion to laparotomy. Overall, 38 patients (3.5%) presented biliary complications and 49 had other local complications (4.5%). Incidence of bile duct injury was 1.2% in the whole series, 2.7% in the open group, and 1.1% in the laparoscopy group. Sixty patients had general complications (5.5%). The overall mortality rate was 0.8%. All patients who died were in poor general condition [American Society of Anesthesiologists (ASA) III or IV].Conclusions: Although laparoscopic cholecystectomy is currently considered as the standard treatment for acute cholecystitis, an open approach is still a valid option in more advanced disease. However, overall mortality and incidence of bile duct injury remain high. [ABSTRACT FROM AUTHOR]

Background: In the era of fast-track surgery, because pancreaticoduodenectomy (PD) carries a significant morbidity, surgeons hesitate to begin early oral feeding and achieve early discharge. We compared the outcome of two different approaches to the postoperative management of PD in two tertiary centers., Methods: Of patients having undergone PD for malignancy from 2008 to 2017, 100 patients who received early postoperative oral feeding (group A) were compared to 100 patients from another center who received early enteral feeding and a delayed oral diet (group B). Surgical indication and approach and type of pancreatic anastomosis were similar between both groups. Postoperative outcomes were retrospectively reviewed., Results: Patient characteristics were similar between both groups, except significantly more neoadjuvant treatment in group A (A = 20% vs. B = 9%, p < 0.01). Mortality rates were 3% and 4% in groups A and B, respectively (p = 0.71). The rate of severe postoperative morbidity was significantly lower in group A (13% vs. 26%, p = 0.02), resulting in a lower reoperation rate (p < 0.01). Delayed gastric emptying and clinically relevant pancreatic fistula were similar between both groups but chyle leaks were more frequent in group A (10% vs. 3%, p = 0.04). The median hospital stay was shorter in group A (16 vs. 20 days, p < 0.01)., Conclusion: In the present study, early postoperative oral feeding after PD was associated with a shorter hospital stay and did not increase severe postoperative morbidity or the rate of pancreatic fistula. However, it resulted in more chyle leaks and did not prevent delayed gastric emptying.

Background: Management of bile duct injury (BDI) after cholecystectomy is challenging. The authors analyzed their center's 49-year experience. Methods: From 1968 to 2016, 120 consecutive patients were managed in a tertiary HBP center, 105 referred from other centers (Group A), 15 from our center (Group B). Surgical strategies and long-term outcomes were retrospectively reviewed. Results: Primary cholecystectomy approach was open in 35% and laparoscopic in 65%. In Group A, intraoperative BDI diagnosis was made in 25/105 patients, including 13 via intraoperative cholangiography (IOC) which was used in 21% of cases. Median time from BDI to referral was 148 days (range 0-10,758), and 3 patients had BDI-related secondary cirrhosis. Ninety-four patients underwent secondary surgical repair, mostly a complex biliary procedure (97%). Postoperative overall and severe morbidity rates were 26% and 6%, respectively. One patient with biliary cirrhosis at referral died postoperatively from hepatic failure. Nine patients (9.6%) developed a secondary biliary stricture after a median of 54 months from repair (6-228 months). In Group B, IOC was performed in 14/15 in whom BDI were intraoperatively detected and immediately repaired. There were 13 minor and 2 major BDIs, all repaired by uncomplex procedures with uneventful postoperative course. One patient had a secondary biliary stricture after 5 months, successfully treated by temporary endoprosthesis. Conclusion: Late follow-up after primary or secondary repair of BDI is recommended to detect recurrent biliary stricture. Bile duct injuries may occur in a tertiary center, but are intraoperatively detected with routine IOC and immediately repaired resulting in satisfactory outcome.

Background: Mucin-producing hepatic cystic neoplasms (MHCN) are uncommon and potentially malignant. Methods: Nine MHCN were encountered in our centre for over 32 years. Patients' clinical, biological, radiological and pathological features were reviewed. Lesions were classified into Mucinous Cystic Neoplasms (MCN) and Intraductal Papillary Neoplasms of the Bile duct (IPNB) (WHO 2010 classification). Results: Five MCN and 4 IPNB were reviewed. Serum and intracystic tumour markers were insufficient to diagnose malignancy. Complications were encountered in five out of nine patients (56%), mean symptom duration was 26 months (range: 1-132). Three patients were mismanaged pre-referral. Radiological features enabled preoperative diagnosis in eight out of nine patients (89%). Greater tumour size, unilocular lesion and mural nodularity indicated malignancy. Radical tumour excision was achieved in eight patients. One IPNB patient was misdiagnosed and underwent unroofing. For 103 months median follow-up, five out of six patients with benign tumours were alive and disease-free, whereas the misdiagnosed IPNB recurred with fatal malignant transformation seven years later. Among the three patients with malignancies (median follow-up: 77 months), two IPNB died, one from cancer recurrence and one from unrelated causes, whereas the malignant MCN was alive and disease-free. Conclusions: Appropriate MHCN diagnosis is crucial, yet it is often misdiagnosed and mismanaged. The prognosis after complete excision is favourable.

ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:- severe, as soon as possible and within 12 hours for patients with septic shock- moderate, within 48 - 72 hours- mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence., Competing Interests: A. Anderloni has provided consultancy to Boston Scientific (2016 – 2018) and Olympus (2018). M. Barthet’s department received a research grant (2016 – 2018). D. Domagk’s department has received workshop, consultancy, and speaker’s fees from Hitachi (2016 to present), and speaker’s fees and symposia support from Dr. Falk Foundation and Olympus (both 2015 to present). I. Hritz has provided consultancy and training for Olympus (2017 to present) and consultancy to Pentax Medical (2018 to present). G. Paspatis has received sponsorship for invited speeches from Boston Scientific (2014 – 2018). T. Ponchon has been on the advisory board of Olympus (2018) and his department has received clinical research funding from Fujifilm (2018). J. E. van Hooft received lecture fees from Medtronics (2014 – 2015) and provided consultancy to Boston Scientific (2014 – 2016), her department has received research grants from Cook Medical (2014 – 2018) and Abbott (2014 – 2017). E. J. Williams was chair of the British Society of Gastroenterology writing group for guidelines on common bile duct stones (2014 – 2017). L. Aabakken, P. Ah-Soune, M. Arvanitakis, J.-M. Dumonceau, J.-F. Gigot, G. Karamanolis, A. Laghi, G. Manes, A. Mariani, K. Paraskeva, J. Pohl, F. Swahn, R. ter Steege, A. Tringali, and A. Vezakis have no competing interests., (© Georg Thieme Verlag KG Stuttgart · New York.)

Treatment of metastatic colorectal cancer is based upon the assumption that metastases are homogeneous within a patient. We quantified immune cell types of 603 whole-slide metastases and primary colorectal tumors from 222 patients. Primary lesions, and synchronous and metachronous metastases, had a heterogeneous immune infiltrate and mutational diversity. Small metastases had frequently a low Immunoscore and T and B cell score, while a high Immunoscore was associated with a lower number of metastases. Anti-epidermal growth factor receptor treatment modified immune gene expression and significantly increased T cell densities in the metastasis core. The predictive accuracy of the Immunoscore from a single biopsy was superior to the one of programmed cell death ligand 1 (PD-L1). The immune phenotype of the least-infiltrated metastasis had a stronger association with patient outcome than other metastases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The prevalence of chemotherapy associated liver injuries (CALI), especially SOS (sinusoidal obstruction syndrome) and NRH (nodular regenerative hyperplasia) might be reduced since the introduction of routine use of biological agents with chemotherapy in colorectal liver metastases (CRLM)., Methods: One hundred patients with CRLM having undergone at least one liver segment resection were prospectively included, and chemotherapy data recorded. Specimens were reviewed by a single pathologist and CALI were described. Prevalence of CALI was compared to our previous experience published in 2013. NRH diagnosis was performed on reticulin special stain, by contrast to our previous study. Postoperative outcome was analysed., Results: Bevacizumab was more frequently administrated in patients of the present study: 53/100 (53%) compared to 20/151 (13%), p < 0.0001. Overall, in the present series, SOS was only observed in 28/100 (28%) patients compared to 116/151 (77%) in 2013 (p < 0.001). When looking specifically to patients receiving Bevacizumab with Folfox, we observed a reduced SOS prevalence compared to Folfox alone (p = 0.008). A higher prevalence of NRH was found in the present study, related to increased detection accuracy, but in patients receiving Bevacizumab in association with Folfox, this prevalence was also reduced compared to Folfox alone (p = 0.03). Both SOS and NRH were associated with severe complications (p = 0.008 and p = 0.005, respectively) and postoperative liver insufficiency (p < 0.001 and p < 0.01, respectively)., Conclusions: The routine use of Bevacizumab in association with Folfox significantly reduced CALI prevalence, in turn linked to severe postoperative complications., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients., Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided., Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not., Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis., (© The Author 2017. Published by Oxford University Press.)

Background: Pancreaticobiliary maljunctions (PBMs) are congenital anomalies of the junction between pancreatic and bile ducts, frequently associated with bile duct cyst (BDC). BDC is congenital biliary tree diseases that are characterized by distinctive dilatation types of the extra- and/or intrahepatic bile ducts. Todani's types I and IVa, in which dilatation involves principally the main bile duct, are the most frequent. PBM induces pancreatic juice reflux into the biliary tract that is supposed to be one of the main factors of biliary cancer degeneration, although the diagnostic criteria of PBM that can be either morphological and/or functional are not well defined especially in Western series., Objective: The aim of this study was to assess the relative prevalence of PBM in BDC in a large European multicenter study, to analyze the characteristics of PBM and try to propose diagnostic criteria of PBMs based on morphological and/or functional criteria and define the positive, negative predictive values, sensibility and specificity of either criteria., Results: From 1975 to 2012, 263 patients with BDC were analyzed. Among them, 190 (72.2 %) were considered to present PBM. Types I and IVa had a similar rate of PBM association. According to the "AFC classification," 57.2 % had a C-P type, 34.5 % a P-C type and 8.3 % a complex type ("anse-de-seau"). The median length of the common channel in patients with PBM was 15.8 ± 6.8 mm (range 5-40 mm). The median intrabiliary amylase and lipase levels were 65,249 and 172,104 UI/L, respectively. For the diagnostic of PBM, a common channel length of more than 8 mm and an intrabiliary amylase level superior to 8000 UI/L were associated with a predictive positive value and a specificity of more than 90 %. Synchronous biliary cancer had an incidence of 8.7 % in all patients with BDC and PBM 11.1 % in adults. Compared to type IV, the type I BDC was associated with statistically more cancer patients in the presence of PBM., Conclusions: Characteristics of PBM associated with BDC in Western population are quite close to reported Eastern series. The results suggest considering both the intrabiliary value of amylase >8000 UI/L and a length of a common channel >8 mm as appropriate values for positive diagnosis of PBM.

Aim: To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts (BDC) resection., Methods: A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cyst-enterostomy (CE) were compared., Results: Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136)., Conclusion: This is the large series to show that previous CE is associated with poorer short- and long-term results after Todani types I and IVb BDC resection.

Aim: To compare clinical presentation, operative management and short- and long-term outcomes of congenital bile duct cysts (BDC) in adults with children., Methods: Retrospective multi-institutional Association Francaise de Chirurgie study of Todani types I+IVB and IVA BDC., Results: During the 37-year period to 2011, 33 centers included 314 patients (98 children; 216 adults). The adult population included more high-risk patients, with more active, more frequent prior treatment (47.7% vs 11.2%; p < 0.0001), more complicated presentation (50.5% vs 35.7%; p = 0.015), more synchronous biliary cancer (11.6% vs 0%; p = 0.0118) and more major surgery (23.6% vs 2%; p < 0.0001), but this latter feature was only true for type I+IVB BDC. Compared to children, the postoperative morbidity (48.1% vs 20.4%; p < 0.0001), the need for repeat procedures and the status at follow-up were worse in adults (27% vs 8.8%; p = 0.0009). However, severe postoperative morbidity and fair or poor status at follow-up were not statistically different for type IVA BDC, irrespective of patients' age. Synchronous cancer, prior HBP surgery and Todani type IVA BDC were independent predictive factors of poor or fair long-term outcome., Conclusion: BDC is a more indolent disease in children compared to adults, except for Todani type IV-A BDC., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Optimal preoperative treatment before colorectal cancer metastases (CRCM) resection remains unclear. This study evaluated pathological responses (pR) in CRCM resected after chemotherapy alone or combined with angiogenesis or epidermal growth factor receptor (EGFR) inhibitors., Methods: Pathological response was retrospectively evaluated on 264 resected metastases from 99 patients. The proportion of responding metastases after different preoperative treatments was reported and compared. Patient's progression-free survival (PFS) and overall survival (OS) were compared based on pR., Results: The combination of anti-angiogenics with oxaliplatin-based chemotherapy resulted in more pR than when they were combined with irinotecan-based chemotherapy (80% vs 50%; P<0.001). Inversely, the combination of EGFR inhibitors with oxaliplatin-based chemotherapy seemed to induce fewer pR than when they were combined with irinotecan-based treatment (53% vs 72%; P=0.049). Overall survival at 5 years was improved for patients with a pR in all resected metastases compared with those who did not achieve a pR (68.5% vs 32.6%; P=0.023) and this response was the only factor predicting OS in a multivariate analysis., Conclusion: The chemotherapy partner combined with angiogenesis or EGFR inhibitors influenced pR in resected CRCM. In our exploratory analysis anti-angiogenic/oxaliplatin-based regimens and anti-EGFR/irinotecan-based regimens were associated with the highest pR. Prospective randomised trials should be performed to validate these observations.

Background: Because of its known malignant potential, precise histologic diagnosis of intraductal papillary mucinous neoplasm of the pancreas (IPMN) during intraoperative pancreatoscopy (IOP) is essential for complete surgical resection. The impact of IOP on perioperative IPMN patient management was reviewed over 20 years of practice at Cliniques universitaires Saint-Luc, Brussels, Belgium., Study Design: Among 86 IPMN patients treated by pancreatectomy between 1991 and 2013, 21 patients had a dilated main pancreatic duct enabling IOP and were retrospectively reviewed. The IOP was performed using an ultrathin flexible endoscope and biopsy forceps, and specimens of all suspicious lesions underwent frozen section examination., Results: Complete IOP with intraductal biopsies was easily and safely performed in 21 patients, revealing 8 occult IPMN lesions. In 5 cases (23.8%), initially planned surgical resection was modified secondary to IOP: 3 for carcinoma in situ and 2 for invasive carcinoma. The postoperative morbidity rate at 3 months was 25.0% (5 of 20); 1 patient died from septic shock postoperatively and was excluded. Median follow-up was 93 months (range 13 to 248 months). Nineteen of 21 patients were still alive and free of disease at last follow-up (90.5%); there was 1 patient with invasive carcinoma at initial pathology (pT3 N1) who died of pulmonary recurrence 21 months after surgery., Conclusions: Intraoperative pancreatoscopy of the main pancreatic duct combined with intraductal biopsies plays a significant role in the surgical management of IPMN patients and should be used in all patients presenting a sufficiently dilated main pancreatic duct., (Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative pancreatic fistula (POPF) is a major complication after pancreatic surgery and results from an impaired healing of the pancreatic enteric anastomosis. Whether perioperative hemodynamic fluid management aiming to provide an adequate tissue perfusion could influence the occurrence of POPF is unknown. Serum lactate level is a well-recognized marker of decreased tissue perfusion and is known to be associated with higher morbidity and mortality in various postoperative settings. We aimed to determine in a retrospective high-volume center's cohort whether postoperative hyperlactatemia could predict POPF occurrence., Method: We conducted a retrospective analysis of 96 consecutive patients admitted in the intensive care unit (ICU) after pancreaticoduodenectomy or distal pancreatectomy. Univariate analysis was conducted to compare lactate levels at 6 h between patients evolving with versus without POPF. A logistic regression model was developed and included potential confounding factors., Results: POPF occurred in 28 patients (29 %). Serum lactate level 6 h after admission was significantly higher in the POPF group (2.8 mmol/L [95 % confidence interval (CI): 2.1-3.5] versus 1.8 mmol/L [95 % CI: 1.8-2.4], p-value = 0.04) whereas it did not differ at ICU admission or at 12 h. Despite similar cumulative fluid balance, fluid intake and vasopressor use, hyperlactatemia > 2.5 mmol/L (Odds ratio (OR): 3.58; 95 % CI: 1.22-10.48; p-value = 0.020) and red blood cells transfusion (OR: 1.24; 95 % CI: 1.03-1.49; p-value = 0.022) were found to be independent predictive factors of POPF occurrence., Conclusion: In patients undergoing partial pancreatectomy, hyperlactatemia measured 6 h after ICU admission is a predictive factor for the occurrence of POPF. Inflammatory changes after surgery may account for this observation and should be further evaluated.

Objective: The purpose of the study was to analyze clinical presentation, surgical management, and long-term outcome of patients suffering from biliary diverticulum, namely Todani type II congenital bile duct cyst (BDC)., Background: The disease incidence ranges between 0.8% and 5% of all reported BDC cases with a lack of information about clinical presentation, management, and outcome., Methods: A multicenter European retrospective study was conducted by the French Surgical Association. The patients' medical records were included in a Web site database. Diagnostic imaging studies, operative and pathology reports underwent central revision., Results: Among 350 patients with congenital BDC, 19 type II were identified (5.4%), 17 in adults (89.5%) and 2 in children. The biliary diverticulum was located at the upper, middle, and lower part of the extrahepatic biliary tree in 11, 4, and 4 patients (58%, 21%, and 21%, respectively). Complicated presentation occurred in 6 patients (31.6%), including one case of synchronous carcinoma. Surgical techniques included diverticulum excision in all patients. Associated resection of the extrahepatic biliary tree was required in 11 cases (58%) and could be predicted by the presence of complicated clinical presentation. There was no mortality. Long-term outcome was excellent in 89.5% of patients (median follow-uptime: 52 months)., Conclusions: According to the present largest Western series of Todani type II BDC, the type of clinical presentation rather than BDC location, was able to guide the extent of biliary resection. Excellent long-term outcome can be achieved in expert centers.

Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by (111)Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100 × 10(9)/L, response (R) for PC≥30 × 10(9)/L and <100 × 10(9)/L with absence of bleeding, no response (NR) for PC<30 × 10(3)/L or significant bleeding. Laparoscopic splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1-235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR = 1.025 by one-year increase, 95% CI [1.004-1.047], p = 0.020) and pre-operative PC (HR = 0.112 for > 100 versus <=100, 95% CI [0.025-0.493], p = 0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.

Introduction: As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection., Methods: Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (<12 months) after a resection., Results: The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24-85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis., Conclusion: The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months., (© 2014 International Hepato-Pancreato-Biliary Association.)

Objectives: Assessment of proliferation by the Ki-67 labelling index (Ki67-LI) is an important parameter of pancreatic neuroendocrine tumour (pNET) prognosis on resection specimens. Ki67-LI values for grading are not fully established on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to determine the accuracy of Ki67-LI on EUS-FNA to predict a final grade of pNET and to analyse the relationship between cytological grading and progression-free survival (PFS)., Methods: Between 1996 and 2010, 46 pNETs (33 were resected) from 45 patients were diagnosed by EUS-FNA. Ki67-LI was evaluated on cytological and histological material for each tumour and classified according to the 2010 WHO grading system., Results: A very good inter-observer agreement for Ki67-LI on EUS-FNA and surgical specimens, respectively, were obtained. Discrepancies were observed between histology and cytology, especially in grade 2 (G2) tumours, where cytology underestimated grading owing to tumour heterogeneity. Still, EUS-FNA was able to distinguish a poor prognostic group, as the actuarial PFS of cytological (c) G3 tumours was 10 ± 4 months versus 29 ± 7 and 68 ± 10 for cG2 and cG1 tumours, respectively (P < 0.0001)., Conclusion: This study attests the reproducibility of Ki67-LI of pNETs whether counted on cytology or histology with a very good inter-observer correlation. Determination of Ki67-LI on EUS-FNA of pNETs should be included systematically in their prognostic work-up., (© 2013 John Wiley & Sons Ltd.)

Background: Surgical resection of pancreatic metastasis (PM) is the only reported curative treatment for renal cell carcinoma. However, there is currently little information regarding very long-term survival. The primary objective of this study was to determine the 10-year survival of this condition using the largest surgical series reported to date., Methods: Between May 1987 and June 2003, we conducted a retrospective study of 62 patients surgically treated for PM from renal cell carcinoma at 12 Franco-Belgian surgical centers. Follow-up ended on May 31, 2012., Results: There were 27 male (44 %) and 35 female (56 %) patients with a median age of 54 years [31-75]. Mean disease-free interval from resection of primary tumor to reoperation for pancreatic recurrence was 9.8 years (median 10 years [0-25]). During a median follow-up of 91 months [12-250], 37 recurrences (60 %) were observed. After surgical resection of repeated recurrences, overall median survival time was 52.6 months versus 11.2 months after nonoperative management (p = 0.019). Cumulative 3-, 5-, and 10-year overall survival (OS) rates were 72, 63, and 32 %, respectively. The corresponding disease-free survival rates were 54, 35, and 27 %, respectively. Lymph node involvement and existence of extrapancreatic metastases before PM were associated with poor overall survival., Conclusions: Aggressive surgical management of single or multiple PM, even in cases of extrapancreatic disease, should be considered in selected patients to allow a chance of long-term survival.

Background: The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection., Methods: Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined., Results: The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis., Conclusions: Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.

This literature review aimed to critically analyze oncological results of vascular resection during pancreatectomy for adenocarcinoma in the light of the concept evolution of locally advanced tumors and microscopic complete resection. The literature search was conducted in PubMed and Medline for the period June 1994 to December 2012, retaining English as the language of publication. The review of 12 publications indicated that mortality and morbidity rates were not significantly different for pancreatectomy with or without venous resection (VR). Six comparative studies showed worse long-term survival in the VR group, though one meta-analysis, albeit with a significant population heterogeneity, demonstrated that the overall survival between VR and the control group was similar (12% vs. 17%). The compilation of 13 comparative studies showed a significantly lower rate of complete microscopic resection in the VR patient group compared to controls (63% vs. 77%; P = 0.001). Concerning pancreatectomy combined to arterial resection, the literature review indicated a significantly greater mortality and morbidity rate and a lower survival rate compared to pancreatic resection alone. Conflicting results concerning the long-term outcome of VR was due to the heterogeneity of the patient population. Since the only chance to cure patients of pancreatic adenocarcinoma is to obtain free resection margins, VR is a valid therapeutic option. But combined arterial resection to pancreatic resection does not appear to be recommended., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The aim of this study was to compare postoperative outcome and long-term results after management of liver hydatid cysts (LHC) by subadventitial cystectomy (SC) and resection of the protruding dome (RPD) in two tertiary liver surgery centers., Methods: Medical records of 52 patients who underwent SC in one center, and 27 patients who underwent RPD in another center between 1991 and 2011 were reviewed. Patients underwent long-term follow-up, including serology tests and morphological examinations., Results: Postoperative mortality was nil. The rate of severe morbidity was 7.7 and 22% (p = 0.082), while the rate of serological clearing-up was 20 and 13.3% after SC and RPD, respectively (p = 1.000). After a mean follow-up of 41 months (1-197), four patients developed a long-term cavity-related complication (LTCRC) after RPD (including one recurrence) and none after SC (p = 0.012). All LTCRCs occurred in patients with hydatid cysts located at the liver dome; three required an invasive procedure by either puncture aspiration injection re-aspiration (N = 1) or repeat surgery (N = 2)., Conclusions: RPD exposes to specific LTCRC, especially when hydatid cysts are located at the liver dome, while SC allows ad integrum restoration of the operated liver. Therefore, SC should be considered as the standard surgical treatment for LHC in experienced hepato-pancreato-biliary centers.

The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection is controversial. We sought to define the incidence of major and microscopic vascular invasion relative to ICC tumor size, and identify predictors of microscopic vascular invasion in patients with ICC ≥5 cm. A total of 443 patients undergoing surgical resection for ICC between 1973 and 2011 at one of 11 participating institutions were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. As tumor sized increased, the incidence of microscopic vascular invasion increased: <3 cm, 3.6 %; 3-5 cm, 24.7 %; 5-7 cm, 38.3 %; 7-15 cm, 32.9 %, ≥15 cm, 55.6 %; (p < 0.001). Increasing tumor size was also found to be associated with worsening tumor grade. The incidence of poorly differentiated tumors increased with increasing ICC tumor size: <3 cm, 9.7 %; 3-5 cm, 19.8 %; 5-7 cm, 24.2 %; 7-15 cm, 21.1 %; >15 cm, 31.6 % (p = 0.04). The presence of perineural invasion (odds ratio [OR] = 2.98) and regional lymph node metastasis (OR = 4.43) were independently associated with an increased risk of microscopic vascular invasion in tumors ≥5 cm (both p < 0.05). Risk of microscopic vascular invasion and worse tumor grade increased with tumor size. Large tumors likely harbor worse pathologic features; this information should be considered when determining therapy and prognosis of patients with large ICC.

Importance: Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the liver that is increasing in incidence, and the prognostic factors associated with outcome after surgery remain poorly defined., Objective: To combine clinicopathologic variables associated with overall survival after resection of ICC into a prediction nomogram., Design, Setting, and Participants: We performed an international multicenter study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from May 1, 1990, through December 31, 2011. Multivariate Cox proportional hazards regression modeling with backward selection using the Akaike information criteria was used to select variables for construction of the nomogram. Discrimination and calibration were performed using Kaplan-Meier curves and calibration plots., Interventions: Surgical resection of ICC at a participating hospital., Main Outcomes and Measures: Long-term survival, effect of potential prognostic factors, and performance of proposed nomogram., Results: Median patient age was 59.2 years, and 53.1% of the patients were male. Most patients (74.7%) had a solitary tumor, and median tumor size was 6.0 cm. Patients were treated with an extended hepatectomy (202 [39.3%]), a hemihepatectomy (180 [35.0%]), or a minor liver resection (<3 segments) (132 [25.7%]). Most patients underwent R0 resection (87.9%), and 35.7% of patients had N1 disease. Using the backward selection of clinically relevant variables, we found that age at diagnosis (hazard ratio [HR], 1.31; P < .001), tumor size (HR, 1.50; P < .001), multiple tumors (HR, 1.58; P < .001), cirrhosis (HR, 1.51; P = .08), lymph node metastasis (HR, 1.78; P = .01), and macrovascular invasion (HR, 2.10; P < .001) were selected as factors predictive of survival. On the basis of these factors, a nomogram was created to predict survival of ICC after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.692)., Conclusions and Relevance: On the basis of an Eastern and Western experience, a nomogram was developed to predict overall survival after resection for ICC. Validation revealed good discrimination and calibration, suggesting clinical utility to improve individualized predictions of survival for patients undergoing resection of ICC.

Objective: To assess clinical presentation and long-term results of surgical management of congenital intrahepatic bile duct dilatation (IHBDD) (Caroli disease and syndrome) in a multicenter setting., Background: Congenital IHBDD predisposes to biliary stasis, resulting in intrahepatic lithiasis, septic complications, and cholangiocarcinoma. Although liver resection (LR) is considered to be the treatment of choice for unilobar disease extent into the liver, the management of bilobar disease and/or associated congenital hepatic fibrosis remains challenging., Methods: From 1978 to 2011, a total of 155 patients (median age: 55.7 years) were enrolled from 26 centers. Bilobar disease, Caroli syndrome, liver atrophy, and intrahepatic stones were encountered in 31.0%, 19.4%, 27.7%, and 48.4% of patients, respectively. A complete resection of congenital intrahepatic bile ducts was achieved in 90.5% of the 148 patients who underwent surgery., Results: Postoperative mortality was nil after anatomical LR (n = 111) and 10.7% after liver transplantation (LT) (n = 28). Grade 3 or higher postoperative morbidity occurred in 15.3% of patients after LR and 39.3% after LT. After a median follow-up of 35 months, the 5-year overall survival rate was 88.5% (88.7% after LT), and the Mayo Clinic score was considered as excellent or good in 86.0% of patients. The 1-year survival rate was 33.3% for the 8 patients (5.2%) who presented with coexistent cholangiocarcinoma., Conclusions: LR for unilobar and LT for diffuse bilobar congenital IHBDD complicated with cholangitis and/or portal hypertension achieved excellent long-term patient outcomes and survival. Because of the bad prognosis of cholangiocarcinoma and the sizeable morbidity-mortality after LT, timely indication for surgical treatment is of major importance.

Objectives: The most frequent presentation of chemotherapy-related toxicity in colorectal liver metastases (CRLM) is sinusoidal obstruction syndrome (SOS). The purpose of the present study was to identify preoperative factors predictive of SOS and to establish associations between type of chemotherapy and severity of SOS., Methods: A retrospective study was carried out in a tertiary academic referral hospital. Patients suffering from CRLM who had undergone resection of at least one liver segment were included. Grading of SOS on the non-tumoral liver parenchyma was accomplished according to the Rubbia-Brandt criteria. A total of 151 patients were enrolled and divided into four groups according to the severity of SOS (grades 0-3)., Results: Multivariate analysis identified oxaliplatin and 5-fluorouracil as chemotherapeutic agents responsible for severe SOS lesions (P < 0.001 and P = 0.005, respectively). Bevacizumab was identified as having a protective effect against the occurrence of SOS lesions (P = 0.005). Univariate analysis identified the score on the aspartate aminotransferase : platelets ratio index (APRI) as the most significant biological factor predictive of severe SOS lesions. Splenomegaly is also significantly associated with the occurrence of severe SOS lesions., Conclusions: The APRI score and splenomegaly are effective as factors predictive of SOS. Bevacizumab has a protective effect against SOS., (© 2013 International Hepato-Pancreato-Biliary Association.)

Introduction: Gallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed "benign" disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry., Methods: Data on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival., Results: Among 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision., Conclusion: In patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment., (Copyright © 2013. Published by Elsevier Masson SAS.)

Introduction: Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC., Methods: We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed., Results: During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size ≥ 5 cm (HR, 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively., Conclusion: Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background and Aims: The objective of this report was to determine the prevalence of underlying nonalcoholic steatohepatitis in resectable intrahepatic cholangiocarcinoma., Methods: Demographics, comorbidities, clinicopathologic characteristics, surgical treatments, and outcomes from patients who underwent resection of intrahepatic cholangiocarcinoma at one of eight hepatobiliary centers between 1991 and 2011 were reviewed., Results: Of 181 patients who underwent resection for intrahepatic cholangiocarcinoma, 31 (17.1 %) had underlying nonalcoholic steatohepatitis. Patients with nonalcoholic steatohepatitis were more likely obese (median body mass index, 30.0 vs. 26.0 kg/m(2), p < 0.001) and had higher rates of diabetes mellitus (38.7 vs. 22.0 %, p = 0.05) and the metabolic syndrome (22.6 vs. 10.0 %, p = 0.05) compared with those without nonalcoholic steatohepatitis. Presence and severity of hepatic steatosis, lobular inflammation, and hepatocyte ballooning were more common among nonalcoholic steatohepatitis patients (all p < 0.001). Macrovascular (35.5 vs. 11.3 %, p = 0.01) and any vascular (48.4 vs. 26.7 %, p = 0.02) tumor invasion were more common among patients with nonalcoholic steatohepatitis. There were no differences in recurrence-free (median, 17.0 versus 19.4 months, p = 0.42) or overall (median, 31.5 versus 36.3 months, p = 0.97) survival after surgical resection between patients with and without nonalcoholic steatohepatitis., Conclusions: Nonalcoholic steatohepatitis affects up to 20 % of patients with resectable intrahepatic cholangiocarcinoma.

Background/aims: Idiopathic pancreatitis is considered to be a multigenic and multifactorial disease. Genetically determined pancreatitis is associated with mutations in the PRSS1,SPINK1 and CFTR genes. This study aimed at examining the clinical and morphological characteristics of patients diagnosed with genetically determined sporadic pancreatitis., Methods: Inclusion criteria were the presence of PRSS1,CFTR or SPINK1 gene mutations in patients with idiopathic recurrent or chronic pancreatitis. Patients with hereditary pancreatitis were excluded. Age- and sex-matched patients with idiopathic pancreatitis and negative genetic testing served as controls (n = 68)., Results: Genetic testing was performed in 351 probands referred to our centre since 1999. Sixty-one patients (17.4%) carried at least 1 detected mutation in 1 of the 3 tested genes (34 CFTR, 10 PRSS1 and 13 SPINK1 mutations), and 4 patients showed a combination of mutations. Follow-up has been currently extended to a median of 5 years (range 1-40). Similar clinical features were noted in the case and matched groups except for an earlier age of onset of pancreatic symptoms and a higher incidence of pancreatic cancer in the case group and in patients with CFTR mutations compared to the control group (p < 0.05). The standardized incidence ratio, the ratio of observed to expected pancreatic cancers, averaged 26.5 (95% confidence interval 8.6-61.9). All pancreatic cancer patients were smokers., Conclusion: Clinical parameters of patients with sporadic idiopathic pancreatitis and gene mutations are similar to those of age- and sex-matched patients without gene mutations, except for the age of pancreatic disease onset. A significantly higher occurrence of pancreas cancer was observed in the case group, particularly in those patients carrying CFTR mutations. We therefore suggest to include patients with CFTR variants presenting with risk factors in a screening and surveillance programme and to strongly advise them to stop smoking., (Copyright © 2013 S. Karger AG, Basel.)

Background: Indications for preoperative biliary drainage (PBD) in the context of hepatectomy for hilar malignancies are still debated. The aim of this study was to investigate current European practice regarding biliary drainage before hepatectomy for Klatskin tumours., Methods: This was a retrospective analysis of all patients who underwent formal or extended right or left hepatectomy for hilar cholangiocarcinoma between 1997 and 2008 at 11 European teaching hospitals, and for whom details of serum bilirubin levels at admission and at the time of surgery were available. PBD was performed at the physicians' discretion. The primary outcome was 90-day mortality. Secondary outcomes were morbidity and cause of death. The association of PBD and of preoperative serum bilirubin levels with postoperative mortality was assessed by logistic regression, in the entire population as well as separately in the right- and left-sided hepatectomy groups, and was adjusted for confounding factors., Results: A total of 366 patients were enrolled; PBD was performed in 180 patients. The overall mortality rate was 10·7 per cent and was higher after right- than left-sided hepatectomy (14·7 versus 6·6 per cent; adjusted odds ratio (OR) 3·16, 95 per cent confidence interval 1·50 to 6·65; P = 0·001). PBD did not affect overall postoperative mortality, but was associated with a decreased mortality rate after right hepatectomy (adjusted OR 0·29, 0·11 to 0·77; P = 0·013) and an increased mortality rate after left hepatectomy (adjusted OR 4·06, 1·01 to 16·30; P = 0·035). A preoperative serum bilirubin level greater than 50 µmol/l was also associated with increased mortality, but only after right hepatectomy (adjusted OR 7·02, 1·73 to 28·52; P = 0·002)., Conclusion: PBD does not affect overall mortality in jaundiced patients with hilar cholangiocarcinoma, but there may be a difference between patients undergoing right-sided versus left-sided hepatectomy., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) recognizing HNF1 α -inactivated HCA (H-HCA), inflammatory HCA (IHCA), and β -catenin-activated HCA (b-HCA). We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25%) characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5%) showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%), b-HCA with GS and β -catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5%) remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of β -catenin-activated/HNF1 α -inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of β -catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities.

Purpose: Tumor progression while receiving neoadjuvant chemotherapy (PD) has been associated with poor outcome and is commonly considered a contraindication to liver resection (LR). This study aims to clarify in a large multicenter setting whether PD is always a contraindication to LR., Methods: Data from the LiverMetSurvey international registry were analyzed. Patients undergoing LR for colorectal metastases without extrahepatic disease after neoadjuvant chemotherapy between 1990 and 2009 were reviewed., Results: Among 2143 patients, PD occurred in 176 (8.2 %). Risk of progression was increased after 5-FU or irinotecan (22.7 % vs. 6.8 % after other regimens, p < 0.0001; 14.9 % vs. 7.2 %, p < 0.0001), while it was reduced after oxaliplatin (5.6 % vs. 12.0 %, p < 0.0001) and still diminished among patients receiving targeted therapies (2.6 %). PD was an independent prognostic factor of survival at multivariate analysis (35 % vs. 49 %, p = 0.0006). In the PD group, 3 independent prognostic factors were identified: carcinoembryonic antigen (CEA) ≥ 200 ng/mL (p = 0.003), >3 metastases (p = 0.028), and tumor diameter ≥ 5 0 mm (p = 0.002). A survival predictive model showed that patients without any risk factors had 5-year survival rates of 53.3 %; good survival results were still observed if metastases were >3 or ≥ 50 mm (29.9 and 19.1 %, respectively). On the contrary, survival was less than 10 % at 3 years in the presence of >1 prognostic factor or CEA of ≥ 200 ng/mL., Conclusions: PD is a negative prognostic factor, but it is not an absolute contraindication to LR. Patients with PD could be scheduled for LR except for those with >3 metastases and ≥ 50 mm, or CEA ≥ 200 ng/mL in whom further chemotherapy is recommended.

Inflammatory myofibroblastic tumors are rare, especially in the pancreas. It is sometimes difficult to obtain a definitive diagnosis with radiological imaging and there is not yet consensus about treatment. We report a case of a 56-year-old man with recurrent abdominal pain particularly in the right upper quadrant without other symptoms. The imaging results showed a pancreatic hypovascularized mass with stenosis of the main pancreatic duct and the common bile duct without metastasis. The FDG PET scanner showed two hypermetabolic foci in the head of the pancreas. The biopsies of the mass were not diagnostic. The therapy adopted was Whipple's pancreaticoduodenectomy with a histological diagnosis of the inflammatory myofibroblastic tumor.

Background: Cholangiocarcinoma (CC) is a rare cancer of the liver. Surgery offers the only chance for cure. When surgery is unfeasible, chemotherapy is the backbone of treatment. The combined administration of cisplatin and gemcitabine is considered standard of care. Human equilibrative nucleoside transporter 1 (hENT1) is the major transporter responsible for gemcitabine uptake into cells. hENT1 expression is associated with an increased survival for patients receiving gemcitabine after pancreatic cancer surgery, suggesting that hENT1 is predictive of response to gemcitabine., Aim: To determine whether there is a correlation between the expression of hENT1 and disease outcome in CC., Methods: A retrospective study on 43 patients treated at our centre with a locally advanced or metastatic CC, who received first line treatment with gemcitabine, was performed., Results: For the whole population, median Progression Free Survival (PFS) and overall survival (OS) were 4.0 (95% Confidence Interval 2.7-5.3 months) and 10.0 months (95%CI 6.8-13.2 months), respectively. From the 26 samples available for hENT1 staining, 18 (69%) and 8 (31%) patients had high and low hENT1 immunostaining, respectively. The median PFS were 2.0 versus 6.0 months for low versus high staining respectively (p = 0.012). The median OS were 5.0 versus 11.0 months for low versus high staining, respectively (p = 0.036). On multivariate analysis, hENT1 expression was the single independent predictive factor associated with prolonged PFS (HR 0.35, p = 0.023) and OS (HR 0.41, p = 0.046)., Conclusion: In this study we show the potential of hENT1 expression as a predictor of outcome in CC treated with gemcitabine. Larger studies are necessary to confirm these promising results., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Laparoscopic surgery is associated with reduced surgical trauma, therefore with acute-phase response of lower magnitude as compared with open surgery. We hypothesized that NOTES might induce reduced immune response as compared with laparoscopy., Objective: To compare acute-phase reactants in a controlled trial of laparoscopic peritoneoscopy and ultrasonography versus transgastric or transcolonic NOTES peritoneoscopy and intraperitoneal endoscopic US., Methods: Eighteen pigs were divided in 3 groups: laparoscopy, transgastric and transcolonic NOTES. Serum levels of IL-6 and TNF-α were determined preoperatively and at day 2. Serum levels of haptoglobin and IL-6 mRNA levels from isolated white blood cells were measured by RT-PCR at days 0, 1, 2 and 7. Necropsy was performed at sacrifice, with peritoneal fluid microbiological analysis, macroscopic and microscopic examinations on gastrotomy/colotomy or abdominal wall closure sites, liver and parietal peritoneum biopsy sites and any area suggestive of infection., Results: The groups were similar with regards to peritoneoscopy completeness, ultrasonographic examination and biopsies. The duration of NOTES procedures was significantly longer than laparoscopic procedures. Minor complications were observed in most animals by macroscopic and microscopic examination, but NOTES procedures were associated with severe complications in 3 pigs (fistula, abscess, mortality). No significant differences in acute-phase reactants levels were found between groups., Conclusions: No significant difference in the acute-phase reactants could be demonstrated between surgical and NOTES procedures. NOTES was however associated with more severe septic complications. Optimal closure remains a challenge and better devices are needed to avoid them.

Purpose: To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival., Patients and Methods: From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses., Results: Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20; P < .001), multiple lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P < .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0; P < .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34)., Conclusion: Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.

Background/aims: Undiagnosed occlusive disease of celiac trunk and/or superior mesenteric artery may lead to life-threatening complications after pancreatoduodenectomy., Methodology: Retrospective analysis of a consecutive series of 171 patients scheduled for pancreatico- duodenectomy or total pancreatectomy., Results: The prevalence of arterial occlusive disease was 5.9% (10 patients), including complete celiac artery occlusive disease in 2 patients (1.2%). Preoperative diagnosis was achieved in 90% of the patients by lateral-views of imaging studies. In arterial stenosis <50% (3 patients), abstention was always successful. In arterial stenosis >50%, successful treatment options included abstention (n=1), preoperative endovascular dilatation (n=1) or stenting (n=1), division of the median arcuate ligament with (n=1) or without (n=1) postoperative endovascular stenting, and aorto-hepatic bypass (2 patients). No early postoperative ischemic complications occurred. However, one patient died from late intestinal ischemia., Conclusions: Arterial occlusive disease is rare in patients undergoing pancreatico-duodenectomy but expose the patient to severe complications if undiagnosed. A tailored management according to the type of arterial stenosis, to patients' indication for surgery and to patients' arterial anatomy is indicated. Surgical and endovascular management may be successfully combined.