Hepatobiliary Pancreat Dis Int

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Hepatobiliary Pancreat Dis Int

	2018 Vol. 17 No. 5
	Published: 2018-10-15


	Pages 381-482
	EDITORIAL REVIEW ARTICLES ORIGINAL ARTICLES/Transplantation ORIGINAL ARTICLES/Liver ORIGINAL ARTICLES/Biliary ORIGINAL ARTICLES/Pancreas LETTERS TO THE EDITOR

EDITORIAL

	381	Lin JZ, Bai Y, Wang AQ, Long JY, Xu WY, Hu K, Zhao L, Pan J, Sang XT, Zhao HT
		Multidisciplinary management of hepatobiliary tumors in the era of precision medicine
		Hepatobiliary tumor (HBT), one of the leading causes of cancer deaths globally, is more frequent in East Asia including China [1] . HBT includes liver cancer, cholangiocarcinoma and gallbladder cancer. HBT burden varies markedly by gender and geographic region due to the exposure of risk factors. Majority of the hepatocellular carcinomas are associated with hepatitis B-type virus infection [2] , and approximate 70% patients were male in China. Other risk factors include infections (hepatitis C virus), aflatoxins, flukes in endemic areas, behavioral factors (alcohol, tobacco), metabolic factors (diabetes, obesity) and congenital disease (bile duct cyst). The pathogenesis of HBTs are complex and HBTs possess high-level tumor heterogeneity (both intra- and inter-tumor) [3,4] , it is important to conduct a comprehensive assessment for every patient before making decision in treatment, which needs multidisciplinary management efforts.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 381-382 . [Abstract] ( 322 ) [HTML 1KB] [PDF 0KB] ( 224 )

	383	Wang WQ, Liu L, Ni QX, Yu XJ
		Guidelines for the diagnosis and treatment of pancreatic adenocarcinoma (2018 edition): A standardized procedure recommended in China
		Pancreatic adenocarcinoma is the fifth leading cause of cancerrelated deaths worldwide, and this incidence is projected to increase further in future decades [1] . Furthermore, despite years of attempting to improve treatment for patients with pancreatic adenocarcinoma, the 5-year overall survival rate remains low at < 7% [2] . Thus, this cancer is devastating, and effective treatment strategies are desperately needed. Although the available diagnosis and treatment measures do not significantly improve patient outcomes, several years of hard work have revolutionized the field using new concepts from medical oncology and produced several scientific advances in the diagnosis and treatment of pancreatic adenocarcinoma.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 383-384 . [Abstract] ( 329 ) [HTML 1KB] [PDF 0KB] ( 203 )

	385	Zhu JQ, He Q, Li XL
		Liver transplantation benefits selected patients with hilar cholangiocarcinoma and colorectal liver metastases
		Hilar cholangiocarcinoma (HCCA) is an aggressive malignancy with a dismal prognosis. The 5-year survival rate has been reported to range from 39% to 50% if an R0 resection is obtained [1] . Approximately 25% patients with early stage HCCA of all cases can be treated with radical surgical resection [2] , while most patients do not have a chance to receive a surgical procedure due to the advanced stage at the time of diagnosis. The poor prognosis is generally attributed to peri–operative mortality, high rates of local tumor recurrence and an insensitive response to systemic treatment. HCCA is traditionally considered to show an unsustained response to chemotherapy. Application of radiotherapy is limited as the special location of tumor would easily lead to severe liver damage. Among unresectable patients, the introduction of catheter-based brachytherapy has showed favorable results, yet, no prospective randomized controlled trial has evealed the survival benefit of local therapy. Presently, liver transplantation has been applied in an attempt to attain a better prognosis for patients with intrahepatic metastases, especially those who have lost the chance to receive a radical resection.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 385-386 . [Abstract] ( 268 ) [HTML 1KB] [PDF 0KB] ( 173 )

REVIEW ARTICLES

	387	Jia JJ, Li JH, Yu H, Nie Y, Jiang L, Li HY, Zhou L, Zheng SS
		Machine perfusion for liver transplantation: A concise review of clinical trials ^Hot!
		BACKGROUND: With the increased use of extended-criteria donors, static cold storage has failed to provide optimal preservation of liver grafts, resulting in early allograft dysfunction and long-term complications. Machine perfusion (MP) is a beneficial alternative preservation strategy for donor livers, particularly for those considered to be of suboptimal quality, and could expand the limited donor pool. DATA SOURCES: A comprehensive search in PubMed, EMBASE, Ovid databases and ClinicalTrials.gov website was conducted using the medical subject heading terms "machine perfusion", "machine preservation", "liver transplantation", combined with free text terms such as "hypothermic", "normothermic" and "subnormothermic". The deadline for the search was September 30, 2017. RESULTS: MP can be classified as hypothermic, subnormothermic, and normothermic with the temperature maintained at 0-12 °C, 25-34 °C and 35-38 °C, respectively. Twelve clinical trials of MP have been reported in recent years. MP effectively decreased AST/ALT level and the incidence of early allograft dysfunction. However, the graft and patient survival rate after MP were similar to static cold storage. The detailed clinical characteristics such as liver function, graft survival, patient survival and early allograft dysfunction were reviewed. CONCLUSIONS: Clinical trial results showed that MP improves delayed graft function, primary non-function and biliary strictures. However, MP still requires validation in large clinical trials and the key parameters during MP still require optimization.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 387-391 . [Abstract] ( 565 ) [HTML 1KB] [PDF 0KB] ( 202 )

ORIGINAL ARTICLES/Transplantation

	392	Pan Q, Cheng Y, Shao ZG, Wang AY, Liu YF
		Prediction of rat liver transplantation outcomes using energy metabolites measured by microdialysis ^Hot!
		BACKGROUND: Warm ischemia jeopardizes graft quality and recipient survival in donation after cardiac death (DCD) transplantation. Currently, there is no system to objectively evaluate the liver quality from DCD. The present study tried to use energy metabolites to evaluate the donor liver quality. METHODS: We divided 195 Sprague-Dawley rats into five groups: the control (n=39), warm ischemic time (WIT) 15?min (n=39), WIT 30?min (n=39), WIT 45?min (n=39), and WIT 60min (n=39) groups. Three rats from each group were randomly selected for pretransplant histologic evaluation of warm ischemia-related damage. The remaining 36 rats were randomly divided into donors and recipients of 18 liver transplantations, and were subjected to postoperative liver function and survival analyses. Between cardiac arrest and cold storage, liver energy metabolites including glucose, lactate, pyruvate, and glycerol were measured by microdialysis. The lactate to pyruvate ratio (LPR) was calculated. RESULTS: The changes in preoperative pathology with warm ischemia were inconspicuous, but the trends in postoperative pathology and aminotransferase levels were consistent with preoperative energy metabolite measurements. The 30-day survival rates of the control and WIT 15, 30, 45, and 60min groups were 100%, 81.82%, 76.92%, 58.33%, and 25.00%, respectively. The areas under the receiver operating characteristic curves of glucose, lactate, glycerol, and LPR were 0.87, 0.88, 0.88, and 0.92, respectively. CONCLUSION: Glucose, lactate, glycerol, and LPR are predictors of graft quality and survival outcomes in DCD transplantation.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 392-401 . [Abstract] ( 275 ) [HTML 1KB] [PDF 0KB] ( 185 )

ORIGINAL ARTICLES/Liver

	402	Martin D, Lykoudis PM, Jones G, Highton D, Shaw A, James S, Wei Q, Fusai G
		Impact of postoperative intravenous fluid administration on complications following elective hepato-pancreato-biliary surgery
		BACKGROUND: The impact of perioperative intravenous fluid administration on surgical outcomes has been documented in literature, but not specifically studied in the context of hepato-pancreato-biliary (HPB) surgery. This study aimed to investigate the impact of postoperative intravenous fluid administration on intensive care unit (ICU), in this subgroup of patients. METHODS: A single-center retrospective cohort of 241 HPB patients was assessed, focusing on intravenous fluid administration in ICU, during the first 24 h. Intravenous fluid variables were compared to hospital stay and postoperative complications. Data were assessed using Spearman's correlation test for bivariate correlations and logistic regression for multivariate analysis. RESULTS: The median volume of intravenous fluid administered in the first 24 h postoperatively was 4380?mL, of which 2200?mL was crystalloid, 1500?mL colloid and 680?mL "other" fluid. Patients with one or more complications had a higher median total intravenous fluid input (4790?vs. 4300?mL), higher colloid volume (2000?vs. 1500?mL), lower urine output (1595?vs. 1900?mL) and greater overall fluid balance (+3040?vs.+2553?mL) than those without complications. There were correlations between total intravenous fluid volume administered (r?=?0.278, P?<?0.001), intravenous colloid input (r?=?0.278, P?<?0.001), urine output (r?=?-0.295, P?<?0.001), positive fluid balance (r?=?0.344, P?<?0.001) and length of hospital stay. Logistic regression model was constructed to predict the occurrence of one or more complications; total intravenous fluid volume and overall fluid balance were both independent significant predictors (OR?=?2.463, P?=?0.007; OR?=?1.001, P?=?0.011; respectively). CONCLUSIONS: Administration of high volumes of intravenous fluids in the first 24 hours post-HPB surgery, along with higher positive fluid balance is associated with a higher rate of complications and longer hospital stay. Moreover, lower urine output is associated with longer hospital stay. Whether these are the cause of complications or the result of them remains unclear.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 402-407 . [Abstract] ( 251 ) [HTML 1KB] [PDF 0KB] ( 191 )

	408	Pu XY, Zheng DF, Shen A, Gu HT, Wei XF, Mou T, Zhang JB, Liu R
		IL-37b suppresses epithelial mesenchymal transition in hepatocellular carcinoma by inhibiting IL-6/STAT3 signaling
		BACKGROUND: Interleukin-37b (IL-37b), a vital negative regulator of the innate immune system, has been reported to be a tumor inhibitor in different type of cancers. However, little is known about the relationship between IL-37b and hepatocellular carcinoma (HCC). The present study aimed to investigate the potential roles of IL-37b in HCC progression. METHODS: Subjects (n?=?237) were recruited, and serum IL-37b was measured using ELISA. The tumor-suppressive capacity and underlying mechanisms of IL-37b in HCC were investigated in vitro and in vivo. RESULTS: Compared to healthy controls, serum IL-37b levels were elevated in chronic hepatitis B (CHB) patients but decreased significantly in HBV-HCC patients, especially for those with portal venous tumor thrombus. Low level serum IL-37b in HBV-HCC patients correlated with high HCC stage and poor overall survival and disease-free survival. In vitro and in vivo, recombinant human IL-37b inhibited proliferation and metastasis in HCC cells. Furthermore, IL-37b inhibited epithelial mesenchymal transition in HCC cells in vitro by downregulating IL-6, pSTAT3 (Y705), N-cadherin, and vimentin expression and by upregulating E-cadherin expression. These effects were partially reversed by transfection of adenovirus encoding human IL-6. CONCLUSIONS: IL-37b inhibits HCC growth, metastasis and epithelial mesenchymal transition by regulating IL-6/STAT3 signaling. Serum IL-37b may be a biomarker for HBV-HCC and its staging.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 408-415 . [Abstract] ( 250 ) [HTML 1KB] [PDF 0KB] ( 166 )

	416	Yuan CW, Wang ZC, Liu K, Liu DJ
		Incomplete radiofrequency ablation promotes the development of CD133 + cancer stem cells in hepatocellular carcinoma cell line HepG2 via inducing SOX9 expression ^Hot!
		BACKGROUND: Cancer stem cells (CSCs) accelerate the growth of hepatocellular carcinoma (HCC) residual after incomplete radiofrequency ablation (In-RFA). The present study aimed to detect the effects of In-RFA on stemness transcription factors (STFs) expression which are important for the production and function of CSCs, and to find which STFs promote HCC stemness after In-RFA. METHODS: HepG2 cells were used for in vitro and in vivo studies. Flow cytometry and sphere-formation assays were used to detect the level and function of CD133⁺CSCs in the models. PCR array and ELISA were applied to analyze the altered expression of 84 STFs in CD133⁺CSCs in two models. Specific lentiviral shRNA was used to knockdown STFs expression, followed by detecting In-RFA's effects on the levels and function of CD133⁺CSCs. RESULTS: In-RFA was identified to induce CD133⁺CSCs and increase their tumorigenesis ability in vitro and in vivo. The mRNA levels of 84 STFs in CD133⁺CSCs were detected by PCR array, showing that 15 and 22 STFs were up-regulated in two models, respectively. Meanwhile, the mRNA levels of seven common STFs were up-regulated in both models. ELISA assay demonstrated that only the protein of sex determining region Y-box 9 (SOX9) was up-regulated in both models, the protein levels of the other 6 common STFs did not increase in both models. Finally, SOX9 was identified to play an important role in inducing, maintaining stemness and promoting tumorigenesis ability of CD133⁺CSCs in both models. CONCLUSION: In-RFA-induced SOX9 stimulates CD133⁺CSCs proliferation and increases their tumorigenesis ability, suggesting that SOX9 may be a good target for HCC treatment.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 416-422 . [Abstract] ( 387 ) [HTML 1KB] [PDF 0KB] ( 188 )

	423	Wang Y, Zhao L, Jiao FZ, Zhang WB, Chen Q, Gong ZJ
		Histone deacetylase inhibitor suberoylanilide hydroxamic acid alleviates liver fibrosis by suppressing the transforming growth factor-β1 signal pathway
		BACKGROUND: Histone deacetylases (HDACs) inhibitors are new anti-fibrotic drugs that inhibit the activity of hepatic stellate cells. The present study focused on the anti-fibrotic function of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) by suppressing transforming growth factor-β1 (TGF-β1) signaling. METHODS: Male Sprague-Dawley rats were used to induce liver fibrosis with carbon tetrachloride (CCl₄) and LX2 cell (human hepatic stellate cell line) was stimulated by TGF-β1. Both animals and cells were treated with SAHA. The Smad7 and connective tissue growth factor (CTGF) mRNA levels were detected by real-time polymerase chain reaction (PCR). Western blotting was used to examine the protein levels of CTGF, Histone H3 (H3), Smad7, Smad2/3, Acetyl-Histone H3 (AH3), HDAC2, α-smooth muscle actin (α-SMA), HDAC6, p-Smad2/3 and HDAC8. In addition, the TGF-β1 and liver enzyme levels from rat serum were detected. Histopathological changes were examined by hematoxylin and eosin (HE), Sirius red and Masson trichrome staining. The α-SMA expression was detected by immumohistochemical staining. RESULTS: Compared with control group, the TGF-β1 and liver enzyme levels from rat serum, together with the mRNA levels of CTGF and protein levels of CTGF, HDAC2, α-SMA, HDAC6, p-Smad2/3 and HDAC8 were elevated in fibrotic rats (P?<?0.01). But the Smad7 mRNA and AH3 protein levels were notably suppressed in the fibrotic rats (P?<?0.01). Pathological examination showed the typical changes of liver fibrosis in the fibrotic rats. After the treatment with SAHA, the levels of liver enzymes, TGF-β1, CTGF, HDAC2, α-SMA, HDAC6, p-Smad2/3 and HDAC8 were reduced (P?<?0.01) and Smad7 and AH3 protein contents were elevated in liver fibrotic rats (P?<?0.01). Moreover, immumohistochemistry showed that SAHA significantly suppressed the α-SMA protein content in fibrotic liver (P?<?0.01). CONCLUSION: The HDAC inhibitor SAHA alleviated liver fibrosis by suppressing the TGF-β1 signaling.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 423-429 . [Abstract] ( 295 ) [HTML 1KB] [PDF 0KB] ( 183 )

ORIGINAL ARTICLES/Biliary

	430	Shmelev A, Sill AM, Kowdley GC, Sanchez JA, Cunningham SC
		Detecting accidental punctures and lacerations during cholecystectomy in large datasets: Two methods of analysis
		BACKGROUND: After the Institute of Medicine (IOM) report To Err Is Human highlighted the impact of medical errors, the Agency for Healthcare Research and Quality (AHRQ) developed Patient-Safety Indicators (PSI) to improve quality by identifying potential inpatient safety problems. PSI-15 was created to study accidental punctures and lacerations (APL), but PSI-15 may underestimate APLs in populations of patients. This study compares PSI-15 with a more inclusive approach using a novel composite of secondary diagnostic and procedural codes. METHODS: We used Nationwide Inpatient Sample (NIS) data (2000-2012) from AHRQ's Healthcare Cost and Utilization Project (H-CUP). We analyzed PSI-15-positive and -negative cholecystectomies. Cross tabulations identified codes that were significantly more frequent among PSI-15-positive cases; these secondary diagnostic and procedural codes were selected as candidate members of a composite marker (CM) of APL. We chose cholecystectomy patients for study because this is one of the most common general operations, and the large size of NIS allows for meaningful analysis of infrequent occurrences such as APL rates. RESULTS: CM identified 1.13 times more APLs than did PSI-15. Patients with CM-detected APLs were significantly older and had worse mortality, comorbidities, lengths of stay, and charges than those detected with PSI-15. Further comparison of these two approaches revealed that time-series analysis for both APL markers revealed parallel trends, with inflections in 2007, and lowest APL rates in July. CONCLUSIONS: Although CM may yield more false positives, it appears more inclusive, identifying more clinically significant APLs, than PSI-15. Both measures presented similar trends over time, arguing against inflation in PSI-15 reporting. While arguably less specific, CM may increase sensitivity for detecting APL events during cholecystectomies. These results may inform the interpretation of other large population studies of APLs following abdominal operations.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 430-436 . [Abstract] ( 474 ) [HTML 1KB] [PDF 0KB] ( 184 )

	437	Son JH, Lee HS, Lee SH, Bang S, Kang J, Paik WH, Ryu JK, Kim YT
		Revision of bilateral self-expandable metallic stents placed using the stent-in-stent technique for malignant hilar biliary obstruction
		BACKGROUND: Endoscopic biliary decompression using bilateral self-expandable metallic stent (SEMS) placed using the stent-in-stent (SIS) technique is considered favorable for unresectable malignant hilar biliary obstruction (MHBO). However, occlusion of the bilateral SIS placement is frequent and revision can be challenging. This study was performed to investigate the efficacy, the long-term patency and the appropriate approach for revision of occluded bilateral SIS placement in unresectable MHBO. METHODS: From January 2011 to July 2016, thirty-eight patients with unresectable MHBO underwent revision of occluded bilateral SIS placement. Clinical data including success rates and patency of revision, were retrospectively analyzed. RESULTS: The technical success rate of revision was 76.3%. The clinical success rate of revision was 51.7% and mean patency of revision was 49.1 days. No significant predictive factor for clinical failure of revision was observed. The cell size of SEMS was not found to have significant effects on clinical success rates or revision patency. CONCLUSIONS: Revision of occluded bilateral SIS placement for MHBO showed fair patency and clinical success rate. Revision method and cell size of SEMS were not found to influence clinical outcomes.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 437-442 . [Abstract] ( 294 ) [HTML 1KB] [PDF 0KB] ( 177 )

ORIGINAL ARTICLES/Pancreas

	443	El Nakeeb A, El Sorogy M, Ezzat H, Said R, El Dosoky M, Abd El Gawad M, Elsabagh AM, El Hanafy E
		Predictors of long-term survival after pancreaticoduodenectomy for peri-ampullary adenocarcinoma: A retrospective study of 5-year survivors
		BACKGROUND: Pancreaticoduodenectomy (PD) is the standard curative treatment for periampullary tumors. The aim of this study is to report the incidence and predictors of long-term survival (≥?5 years) after PD. METHODS: This study included patients who underwent PD for pathologically proven periampullary adenocarcinomas. Patients were divided into 2 groups: group (I) patients who survived less than 5 years and group (II) patients who survived?≥?5 years. RESULTS: There were 47 (20.6%) long-term survivors (≥?5 years) among 228 patients underwent PD for periampullary adenocarcinoma. Patients with ampullary adenocarcinoma represented 31 (66.0%) of the long-term survivors. Primary analysis showed that favourable factors for long-term survival include age?<?60 years old, serum CEA?<?5?ng/mL, serum CA 19-9?<?37?U/mL, non-cirrhotic liver, tumor size?<?2?cm, site of primary tumor, postoperative pancreatic fistula, R0 resection, postoperative chemotherapy, and no recurrence. Multivariate analysis demonstrated that CA 19-9?<?37?U/mL [OR (95% CI)?=?1.712 (1.248-2.348), P?=?0.001], smaller tumor size [OR (95% CI?)=?1.335 (1.032-1.726), P?=?0.028] and Ro resection [OR (95% CI)?=?3.098 (2.095-4.582), P?<?0.001] were independent factors for survival?≥?5 years. The prognosis was best for ampullary adenocarcinoma, for which the median survival was 54 months and 5-year survival rate was 39.0%, and the poorest was pancreatic head adenocarcinoma, for which the median survival was 27 months and 5-year survival rate was 7%. CONCLUSIONS: The majority of long-term survivors after PD for periampullary adenocarcinoma are patients with ampullary tumor. CA 19-9?<?37?U/mL, smaller tumor size, and R0 resection were found to be independent factors for long-term survival?≥?5 years.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 443-449 . [Abstract] ( 264 ) [HTML 1KB] [PDF 0KB] ( 177 )

	450	Kim NH, Kim HJ
		Preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after curative intent surgical resection
		BACKGROUND: Postoperative early recurrence (ER) in patients with pancreatic ductal adenocarcinoma (PDAC) is frequently encountered after curative intent surgery. Nonetheless, clinical significance and risk factors of ER after surgery for PDAC have not been extensively investigated. The aim of this study was to determine preoperative risk predictors for ER in patients with PDAC after upfront surgery. METHODS: Eighty-one consecutive patients with PDAC who underwent curative intent surgical resection at Kangbuk Samsung Hospital between January 2004 and May 2015 were enrolled. ER was defined as tumor relapse within 6 months after surgery. RESULTS: ER occurred in 26 patients (32.1%), whereas 49 patients (60.5%) had late recurrence (≥?6 months after surgery), and 6 patients had no recurrence (7.4%). Univariate analysis showed that C-reactive protein (CRP)?>?3.0?mg/dL, modified Glasgow prognostic score (mGPS)?=?2, decrease of total lymphocyte count by?>?50% of baseline value in the preoperative period, prognostic nutritional index (PNI) 〈 45, neutrophil-to-lymphocyte ratio (NLR)?≥?3, and preoperative maximum standardized uptake value (SUVmax) were significantly associated with ER. Multivariate logistic regression analysis revealed that CRP 〉 3.0?mg/dL, decrease of total lymphocyte count by?>?50% of baseline value, and preoperative SUVmax were significant and independent contributors of ER in patients with resectable PDAC who underwent curative intent surgery. CONCLUSIONS: Postoperative ER for resectable PDAC was frequent with poor prognosis after curative intent upfront surgery. It is reasonable to suggest that there is a subgroup of resectable PDAC patients at high-risk of ER and neoadjuvant therapy should be considered in these patients in a clinical trial setting.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 450-455 . [Abstract] ( 267 ) [HTML 1KB] [PDF 0KB] ( 187 )

	456	Mowbray NG, Ben-Ismaeil B, Hammoda M, Shingler G, Al-Sarireh B
		The microbiology of infected pancreatic necrosis
		BACKGROUND: Acute pancreatitis (AP) continues to cause significant morbidity and mortality, especially when it leads to infected pancreatic necrosis (IPN). Modern treatment of IPN frequently involves prolonged courses of antibiotics in combination with minimally invasive therapies. This study aimed to update the existing evidence base by identifying the pathogens causing IPN and therefore aid future selection of empirical antibiotics. METHODS: Clinical data, including microbiology results, of consecutive patients with IPN undergoing minimally invasive necrosectomy at our institution between January 2009 and July 2016 were retrospectively reviewed. RESULTS: The results of 40 patients (22 males and 18 females, median age 60 years) with IPN were reviewed. The etiology of AP was gallstones, alcohol, dyslipidemia and unknown in 31, 2, 2 and 5 patients, respectively. The most frequently identified microbes in microbiology cultures were Enterococcus faecalis and faecium (22.5% and 20.0%) and Escherichia coli (20.0%). In 19 cases the cultures grew multiple organisms. The antibiotics with the least resistance amongst the microbiota were teicoplanin (5.0%), linezolid (5.6%), ertapenem (6.5%), and meropenem (7.4%). CONCLUSION: The carbapenem antibiotics, ertapenem and meropenem provide good antimicrobial cover against the common, mainly enteral, microorganisms causing IPN. Culture and sensitivity results of acquired samples should be regularly reviewed to adjust prescribing and monitor for emergence of resistance.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 456-460 . [Abstract] ( 294 ) [HTML 1KB] [PDF 0KB] ( 167 )

	461	Neumann CCM, von Horschelmann E, Reutzel-Selke A, Seidel E, Sauer IM, Pratschke J, Bahra M, Schmuck RB
		Tumor-stromal cross-talk modulating the therapeutic response in pancreatic cancer ^Hot!
		BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor with a dismal prognosis. The stroma component makes up to 90% of the tumor mass and is thought to be one of the main reasons for the tumor's high chemoresistance. Cancer associated fibroblasts (CAFs) have previously been identified to be the key stromal players. This is the first time we provide detailed in vitro experiments investigating tumor-stromal interactions when exposed to three well-known chemotherapeutic agents. METHODS: Monocultures, indirect and direct co-cultures of two PDAC cell lines (AsPC and Panc-1) and six primary patients derived CAFs were treated with gemcitabine, nab-paclitaxel and the γ-secretase-inhibitor (GSI) DAPT. The cell viability of each component was measured with XTT. Finally, IL-6 concentrations of the supernatants were analyzed. RESULTS: On the contrary to PDAC cell lines, CAF monocultures hardly responded to any treatment which suggested that stroma (CAFs) itself is more resistant to standard chemo-treatments than the epithelial cancer cells. Moreover, only a weak chemotherapeutic response was observed in direct co-cultures of cancer cells with CAFs. A change in the morphology of direct co-cultures was accompanied with the chemoresistance. CAFs were observed to build cage-like structures around agglomerates of tumor cells. High levels of IL-6 were also associated with a reduced response to therapy. Indirect co-cultures make the tumor-stromal interaction more complex. CONCLUSIONS: CAFs are highly chemoresistant. Direct cell-cell contact and high levels of IL-6 correlate with a high chemoresistance.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 461-472 . [Abstract] ( 391 ) [HTML 1KB] [PDF 0KB] ( 180 )

LETTERS TO THE EDITOR

	473	Kim SH, Kim KH, Ha TY, Jung DH, Park GC, Lee SG
		Salvage living donor liver transplantation for recurrent hepatocellular carcinoma after prior laparoscopic hepatectomy
		Salvage liver transplantation (LT) is frequently performed on patients who experience recurrent hepatocellular carcinoma (HCC) after primary hepatectomy for HCC [1,2] . The main concern in these patients is the technical feasibility of salvage LT, especially as prior hepatectomy may result in heavy adhesions [3,4] . Salvage living donor LT (LDLT) is a more demanding procedure than salvage deceased donor LT (DDLT) using an entire donor graft with a long vascular pedicle [5,6] . Because less than optimal dissection of perihepatic adhesions could result in uncontrollable pinpoint bleedings at the dissection surface [1,5] , many transplant surgeons avoid performing salvage LDLT. Minimally invasive laparoscopic hepatectomy (LH) results in fewer intraperitoneal adhesions than the open method, reducing the difficulty of surgical dissection during future LT [7–10] . To date, however, no study has compared salvage LDLT for recurrent HCC after LH to that after open hepatectomy (OH).
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 473-476 . [Abstract] ( 239 ) [HTML 1KB] [PDF 0KB] ( 187 )

	477	Mou HB, Li WD, Shen YJ, Shi JP, Guo XD, Yao M, Wang K, Zhang T
		Trastuzumab, not lapatinib, has therapeutic effects on Chinese patients with HER2-positive cholangiocarcinoma
		As a relatively uncommon orphan tumor with high mortality, biliary tract cancer (BTC) presents an aggressive course and heterogeneous clinical features [1] . BTC patients present with advanced manifestations [2] . Unfortunately, there has been little progress in the management of BTC. Most patients have inoperable lesions and must receive palliative therapy. Gemcitabine-based chemotherapy has been the only widely accepted first-line treatment for advanced BTC [3] . Nevertheless, BTCs are often refractory to chemotherapeutic regimens, leading to a poor clinical outcome in these patients. Recently, with the rapid development of next generation sequencing (NGS) technologies, some actionable mutations such as those in IDH1, FGFR2, BRAF, HER2 genes, and unique molecular subsets in BTCs have been identified [4] , and related targeted therapy against actionable mutations has been introduced into clinical practice as a promising therapeutic strategy [5] . The HER2 (also known as ERBB2 ) gene aberration has been recognized as an oncogenic driver and potential target in some human cancers, including breast cancer, lung cancer, and colorectal cancer [6] . To date, it is still an open question whether HER2 gene alterations are clinically relevant in BTC management [7] . Here, we describe a unique case report of two metastatic cholangiocarcinoma patients with different HER2 gene aberrations who had received anti-HER2 targeted therapy but presented significantly different responses, suggesting the importance of individualized medicine for the management of BTC patients, even those with similar mutation profiles.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 477-479 . [Abstract] ( 229 ) [HTML 1KB] [PDF 0KB] ( 183 )

	480	Dalla Pria HRF, Santiago RA, Velloni FG, D'ippolito G
		Bifid pancreatic tail as cause of acute pancreatitis
		We present a case of a 22-year-old woman with recurrent episodes of acute pancreatitis. The patient had no known risk factors such as history of alcoholism, smoking, pre-existing medical conditions, family members with pancreatitis, autoimmune disease or regular use of medications. During the last episode, an amylase peak (1175 U/L) and increased inflammatory markers were detected, along with ultrasonographic confirmation of acute pancreatic inflammation, with no biliary dilatation or cholelithiasis.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 480-481 . [Abstract] ( 239 ) [HTML 1KB] [PDF 0KB] ( 166 )

	482	Xu XF, Yan WT, Wang JH, Xing H, Yang T
		Propensity score analyses of long-term outcomes of perivascular hepatocellular carcinoma: Radiofrequency ablation vs. surgery.
		We read with great interest the article by Dr. Lee et al. [1], which compared the long-term outcomes of patients with perivascular hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) and surgical resection (SR) as first-line treatment. By using propensity score matching (PSM) analyses, the authors concluded that SR provided better long-term tumor control and overall survival than RFA for patients with small periportal tumors. Herein, we would like to raise the following comments.
		Hepatobiliary Pancreat Dis Int. 2018; 17(5): 482-482 . [Abstract] ( 302 ) [HTML 1KB] [PDF 0KB] ( 161 )

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