Hepatobiliary Pancreat Dis Int

	2019 Vol. 18 No. 2
	Published: 2019-04-15


	Pages 101-202
	EDITORIAL META-ANALYSIS REVIEW ARTICLES ORIGINAL ARTICLES/Transplantation ORIGINAL ARTICLES/Liver ORIGINAL ARTICLES/Biliary ORIGINAL ARTICLES/Pancreas LETTERS TO THE EDITOR GUIDELINES

EDITORIAL

	101	Lai Q, Melandro F, Mennini G, Rossi M
		New insights in the management of the middle hepatic vein dilemma
		When the first series of adult-to-adult living donor liver transplantation (A2A-LDLT) were performed in Hong Kong [1] , it was immediately clear that great technical challenges existed, mainly concerning the middle hepatic vein (MHV) tributaries management. In the initial Hong Kong experience, MHV was always included in the graft, with the intent to avoid a severe congestion in the graft right median sector and, consequently, to reduce the risks of mortality for the recipient [2] .
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 101-102 . [Abstract] ( 56 ) [HTML 1KB] [PDF 0KB] ( 121 )

GUIDELINES

	103	Zou WB, Ru N, Wu H, Hu LH, Ren X, Jin G, Wang Z, Du YQ, Cao YN, Zhang L, Chang XY, Zhang RC, Li XB, Shen Y, Li P, Li ZS, Liao Z; Chronic Pancreatitis Group of Chinese Medical Doctor Association
		Guidelines for the diagnosis and treatment of chronic pancreatitis in China (2018 edition) ^Hot!
		Chronic pancreatitis (CP) is a progressive inflammatory disease of pancreas that alters the organ’s normal structure and functions. CP seriously affects the quality of life of patients and greatly in- creases the public medical burden of society. In recent years, the incidence of CP has increased worldwide. The concepts of etiol- ogy and therapies have been continuously updated. Clinical treat- ment guidelines for the disease have been issued in Japan, the United States and Europe. The Chronic Pancreatitis Group of China organized over 80 experts of Gastroenterology, Biliary and Pancre- atic Surgery, Endocrinology, Radiology and Pathology to revise and update the Chinese Guidelines for the Diagnosis and Treatment of Chronic Pancreatitis ( 2012 edition) . The new guidelines are based on the latest medical evidence from China and other countries.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 103-109 . [Abstract] ( 72 ) [HTML 1KB] [PDF 0KB] ( 112 )

META-ANALYSIS

	110	Wang ML, Ke ZY, Yin S, Liu CH, Huang Q
		The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review ^Hot!
		Background: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. Data sources: Relevant research articles published before 1st March 2018 in PubMed, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios (HRs) [95% confidence intervals (CI)] and forest plots. Results: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival (OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone (HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarci- noma group (HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group (HR = 0.60; P < 0.001), R1 resection group (HR = 0.71; P = 0.04), LN-positive diagnosis group (HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group (HR = 0.42; P < 0.001), distal cholangiocarcinoma group (HR = 0.48; P = 0.17), R0 re- section group (HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group (HR = 0.90; P = 0.66), respectively. Conclusions: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 110-116 . [Abstract] ( 56 ) [HTML 1KB] [PDF 0KB] ( 107 )

REVIEW ARTICLES

	117	Wu LM, Zhang LL, Chen XH, Zheng SS
		Is irreversible electroporation safe and effective in the treatment of hepatobiliary and pancreatic cancers?
		Background: Irreversible electroporation (IRE) is a novel ablative technique for hepatobiliary and pancre- atic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepatobiliary and pancreatic cancers. Data sources: Studies were identified by searching PubMed and Embase for articles published in English from database inception through July 31, 2017. For inclusion, each clinical study had to report morbidity and survival data on hepatobiliary and pancreatic cancers treated with IRE and contain at least 10 pa- tients. Studies that met these criteria were included for analysis. Two authors assessed each clinical study for data extraction. The controversial parts were resolved through discussion with seniors. Results: A total of 24 clinical studies were included. Fourteen focused on hepatic ablation with IRE com- prising 437 patients with 666 lesions of different tumor types. Two patients (0.5%) died after the IRE procedure. Morbidity of hepatic ablation with IRE ranged from 7% to 35%. Most complications were mild. Complete response for hepatic tumors was reported as 57%–97%. Ten studies with 455 patients focused on pancreatic IRE. The overall mortality of IRE in pancreatic cancer was 2%. Overall severe morbidity of IRE in pancreatic cancer ranged from 0 to 20%. The median overall survival after IRE ranged from 7 to 23 months. Patients treated with IRE combined with surgical resection showed a longer overall survival. Conclusions: IRE significantly improves the prognosis of advanced hepatobiliary and pancreatic malig- nances, and companied with less complications. Hence, IRE is a relatively safe and effective non-thermal ablation strategy and potentially recommended as an option for therapy of patients with hepatobiliary and pancreatic malignances.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 117-124 . [Abstract] ( 50 ) [HTML 1KB] [PDF 0KB] ( 129 )

ORIGINAL ARTICLES/Transplantation

	125	Guo HJ, Wang K, Chen KC, Liu ZK, Al-Ameri A, Shen Y, Xu X, Zheng SS
		Middle hepatic vein reconstruction in adult right lobe living donor liver transplantation improves recipient survival ^Hot!
		Background: The efficacy and necessity of middle hepatic vein (MHV) reconstruction in adult-to-adult right lobe living donor liver transplantation (LDLT) remain controversial. The present study aimed to eval- uate the survival beneficiary of MHV reconstructions in LDLT. Methods: We compared the clinical outcomes of liver recipients with MHV reconstruction ( n = 101) and without MHV reconstruction ( n = 43) who underwent LDLT using right lobe grafts at our institution from January 2006 to May 2017. Results: The overall survival (OS) rate of recipients with MHV reconstruction was significantly higher than that of those without MHV reconstruction in liver transplantation ( P = 0.022; 5-yr OS: 76.2% vs 58.1%). The survival of two segments (segments 5 and 8) hepatic vein reconstruction was better than that of the only one segment (segment 5 or segment 8) hepatic vein reconstruction ( P = 0.034; 5-yr OS: 83.6% vs 67.4%). The survival of using two straight vascular reconstructions was better than that using Y-shaped vascular reconstruction in liver transplantation with two segments hepatic vein reconstruction ( P = 0.020; 5-yr OS: 100% vs 75.0%). The multivariate analysis demonstrated that MHV tributary reconstructions were an independent beneficiary prognostic factor for OS (hazard ratio = 0.519, 95% CI: 0.282–0.954, P = 0.035). Biliary complications were significantly increased in recipients with MHV reconstruction (28.7% vs 11.6%, P = 0.027). Conclusions: MHV reconstruction ensured excellent outflow drainage and favored recipient outcome. The MHV tributaries (segments 5 and 8) should be reconstructed as much as possible to enlarge the hepatic vein anastomosis and reduce congestion.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 125-131 . [Abstract] ( 57 ) [HTML 1KB] [PDF 0KB] ( 128 )

	132	Iesari S, Inostroza Nunez ME, Rico Juri JM, Ciccarelli O, Bonaccorsi-Riani E, Coubeau L, Laterre PF, Goffette P, De Reyck C, Lengele B, Gianello P, Lerut J
		Adult-to-adult living-donor liver transplantation: The experience of the Universitécatholique de Louvain ^Hot!
		Background: Liver transplantation is the treatment for end-stage liver diseases and well-selected malignancies. The allograft shortage may be alleviated with living donation. The initial UCLouvain experience of adult living-donor liver transplantation (LDLT) is presented. Methods: A retrospective analysis of 64 adult-to-adult LDLTs performed at our institution between 1998 and 2016 was conducted. The median age of 29 (45.3%) females and 35 (54.7%) males was 50.2 years (interquartile range, IQR 32.9–57.5). Twenty-two (34.4%) recipients had no portal hypertension. Three (4.7%) patients had a benign and 33 (51.6%) a malignant tumor [19 (29.7%) hepatocellular cancer, 11 (17.2%) secondary cancer and one (1.6%) each hemangioendothelioma, hepatoblastoma and embryonal liver sarcoma]. Median donor and recipient follow-ups were 93 months (IQR 41–159) and 39 months (22–91), respectively. Results: Right and left hemi-livers were implanted in 39 (60.9%) and 25 (39.1%) cases, respectively. Median weights of right- and left-liver were 810 g (IQR 730–940) and 454 g (IQR 394–534), respectively. Graft-to-recipient weight ratios (GRWRs) were 1.17% (right, IQR 0.98%-1.4%) and 0.77% (left, 0.59%-0.95%). One- and five-year patient survivals were 85% and 71% (right) vs. 84% and 58% (left), respectively. One- and five-year graft survivals were 74% and 61% (right) vs. 76% and 53% (left), respectively. The patient and graft survival of right and left grafts and of very small ( < 0.6%), small (0.6%–0.79%) and large ( ≥0.8%) GRWR were similar. Survival of very small grafts was 86% and 86% at 3- and 12-month. No donor died while five (7.8%) developed a Clavien–Dindo complication IIIa, IIIb or IV. Recipient morbidity consisted mainly of biliary and vascular complications; three (4.7%) recipients developed a small-for-size syndrome according to the Kyushu criteria. Conclusions: Adult-to-adult LDLT is a demanding procedure that widens therapeutic possibilities of many hepatobiliary diseases. The donor procedure can be done safely with low morbidity. The recipient operation carries a major morbidity indicating an important learning curve. Shifting the risk from the donor to the recipient, by moving from the larger right-liver to the smaller left-liver grafts, should be further explored as this policy makes donor hepatectomy safer and may stimulate the development of transplant oncology.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 132-142 . [Abstract] ( 61 ) [HTML 1KB] [PDF 0KB] ( 123 )

ORIGINAL ARTICLES/Liver

	143	Zhao Y, Thurairajah PH, Kumar R, Tan J, Teo EK, Hsiang JC
		Novel non-invasive score to predict cirrhosis in the era of hepatitis C elimination: A population study of ex-substance users in Singapore
		Background: Chronic hepatitis C infection is common among people with history of substance use. Liver fibrosis assessment is a barrier to linkage to care, particularly among those with history of substance users. The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination, especially in countries where transient elastography (TE) is not available. We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population. Methods: HCV patients with history of substance use between 2011 and 2016 were analyzed. All patients had TE for liver fibrosis assessment. Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared. Youden’s index was used to determine optimal cut-off of the novel score. Results: A total of 579 patients were included. In multivariate logistic regression, cirrhosis on TE was associated with age ( P = 0.002), aspartate aminotransferase (AST) ( P = 0.004), and platelet count ( P < 0.001), but not alanine aminotransferase (ALT) ( P = 0.896). These form the components of modified AST-to- platelet ratio index (APRI) score. Modified APRI was superior to APRI in predicting cirrhosis (AUROC, 0.796 vs. 0.770, P = 0.007), but not fibrosis-4 score (FIB-4) ( P = 1.00). Modified APRI at cut-off of 4 has sensitivity, specificity and negative predictive value (NPV) of 94.4%, 26.9% and 92.6%, respectively, and at 19, has sensitivity, specificity and positive predictive value (PPV) of 33.3%, 96.2% and 77.1%, respectively. FIB-4 has a NPV and PPV of 88.6%, 41.8% and 78.5%, 77.6%, at cut-off of 1.45 and 3.25, respectively. Using the cut-offof 4 and 14 for modified APRI, 32.5% of patients can be correctly classified and misses out only 5.6% of cirrhosis patients. Conclusions: Modified APRI score is superior in predicting cirrhosis in HCV population, with 32.5% of the population being correctly classified using cut-off of 4 and 14. Further studies are required to validate the findings.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 143-148 . [Abstract] ( 49 ) [HTML 1KB] [PDF 0KB] ( 102 )

	149	Zhang L, Wu YN, Chen T, Ren CH, Li X, Liu GX
		Relationship between intestinal microbial dysbiosis and primary liver cancer
		Background: Intestinal microbial dysbiosis is involved in liver disease pathogenesis. However, its role in primary liver cancer (PLC), particularly in hepatocarcinogenesis remains unclear. The present study aimed to study the changes in intestinal flora at various stages of PLC and clarify the relationship between intestinal microbes and PLC. Methods: Twenty-four patients with PLC (PLC group), 24 patients with liver cirrhosis (LC group), and 23 healthy control individuals (HC group) were enrolled from October 2016 to October 2017. Stool specimens of the participants were collected and the genomic DNA of fecal bacteria was isolated. High-throughput pyrosequencing of 16S rDNA was used to identify differences in gut bacterial diversity among HC, LC, and PLC groups. We also analyzed the relationship between clinical factors and intestinal microorganisms in LC and PLC groups. Results: Diversity of Firmicutes tended to decrease from the HC to LC and PLC groups at the phylum level. Among species, Enterobacter ludwigii displayed an increasing trend in the PLC group, wherein the relative abundance of Enterobacter ludwigii in the PLC group was 100 times greater than that in the HC and LC groups. The ratio of Firmicutes/Bacteroidetes was significantly decreased with the disease progression. In addition, the linear discriminant analysis effect size method indicated that Clostridia were predominant in the gut microbiota of the HC group, whereas Enterococcaceae, Lactobacillales, Bacilli and Gammaproteobacteria may be used as diagnostic markers of PLC. Redundancy analysis showed a correlation between intestinal microbial diversity and clinical factors AST, ALT, and AFP. Veillonella showed a significant positive correlation with AFP in the PLC group, whereas Subdoligranulum showed a negative correlation with AFP. Conclusions: This study indicates that dysbiosis of the gut microbiota might be involved in PLC development and progression.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 149-157 . [Abstract] ( 53 ) [HTML 1KB] [PDF 0KB] ( 107 )

	158	Tai BJ, Yao M, Zheng WJ, Shen YC, Wang L, Sun JY, Wu MN, Dong ZZ, Yao DF
		Alteration of oncogenic IGF-II gene methylation status associates with hepatocyte malignant transformation ^Hot!
		Background: Oncogenic insulin-like growth factor-II (IGF-II) is overexpressed in hepatocellular carcinoma (HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. Methods: IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration (nmol/mg protein). Status of human IGF-II promoter 3 (P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction (MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay. Results: The levels of hepatic IGF-II expression were significantly elevated in the HCC group ( P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none (0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA (all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level ( r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II ( r s = −0.89, P < 0.001) or liver IGF-II level ( r s = −0.84, P < 0.001). Conclusions: The increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 158-163 . [Abstract] ( 54 ) [HTML 1KB] [PDF 0KB] ( 101 )

	164	Zhang MY, Zhang RJ, Jiang HJ, Jiang H, Xu HL, Pan WB, Wang YQ, Li X
		(18)F-fluoromisonidazole positron emission tomography may be applicable in the evaluation of colorectal cancer liver metastasis
		Background: Positron emission tomography (PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole (FMISO) PET quantitative parameter of maximum standardized uptake value (SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer (CRC) in mice. Methods: Colorectal liver metastases (CRLM) xenograft models were established by injecting tumor cells (LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by sub- cutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. 18 F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. 18 F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the 18 F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1α (HIF-1 α) and serum starvation-induced glucose transporter 1 (GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, 18 F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models es- tablished using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between 18 F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between 18 F-FMISO SUVmax ratio and HIF-1 αor GLUT-1 expression in tumor-bearing tissues. Conclusions: 18 F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 164-172 . [Abstract] ( 53 ) [HTML 1KB] [PDF 0KB] ( 123 )

ORIGINAL ARTICLES/Biliary

	173	Behairy BE, Konswa HA, Ahmed HT, El-Azab DS, Adawy NM, Sira AM
		Serum ferritin in neonatal cholestasis: A specific and active molecule or a non-specific bystander marker? ^Hot!
		Background: Serum ferritin (SF) and consequently hepatic iron have long been considered important in liver fibrosis progression. They have been studied in different liver diseases with no previous reports in neonatal cholestasis (NC). This study aimed to measure SF in different etiologies of NC and investigate its relation to hepatic iron and fibrosis. Methods: SF was measured in 75 infants, including 50 with NC and 25 with sepsis. SF was compared between these two groups. Biochemical parameters, hepatic iron grades, and liver fibrosis and other histopathological characteristics and correlated with SF were assessed in NC group. Finally, a comparison between intrahepatic cholestasis and obstructive etiology was performed. Results: SF was elevated in NC (1598 ±2405 ng/mL) with no significant difference from those with sepsis ( P = 0.445). NC and sepsis constituted augmenting factors leading to more elevation of SF (2589 ±3511 ng/mL). SF was significantly correlated with hepatic iron grades ( r = 0.536, P < 0.0 0 01) and a cut-off value of 803.5 ng/mL can predict higher grades ( ≥grade 3) of iron deposition with sensitivity of 100%, specificity of 70% and accuracy of 85%. Moreover, SF was significantly higher ( P < 0.0 0 01) in those with intrahepatic cholestasis (2602 ±3154 ng/mL) and their prevalent pathological findings of giant cell transformation ( P = 0.009) and hepatocyte swelling ( P = 0.023) than those with obstructive etiology (672 ±566 ng/mL) and their prevalent pathological findings of ductular proliferation ( P = 0.003) and bile plugs ( P = 0.002). SF was unrelated to the grade of liver fibrosis ( P = 0.058). Conclusions: SF is non-specifically elevated in NC, with positive correlation to hepatic iron grades. SF ≥803.5 ng/mL can predict higher grades ( ≥grade 3) of hepatic iron. However, an active role of in- creased SF and hepatic iron in disease progression remains questionable.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 173-180 . [Abstract] ( 58 ) [HTML 1KB] [PDF 0KB] ( 132 )

ORIGINAL ARTICLES/Pancreas

	181	Gupta V, Kumar S, Gupta V, Joshi P, Rahul R, Yadav RK, Dangi A, Chandra A
		Blumgart’s technique of pancreaticojejunostomy: Analysis of safety and outcomes
		Background: Blumgart’s pancreaticojejunostomy (PJ) has been described with low pancreatic leak rates. This study aimed to evaluate our experience with this technique regarding the pancreatic leak and other perioperative outcomes. Methods: We performed a single-center retrospective analysis of a cohort of 81 patients who underwent pancreaticoduodenectomy in our department from January 2011 to February 2018. The primary endpoint was the occurrence of a clinically relevant postoperative pancreatic fistula (CR-POPF) and analysis of its risk factors. Results: The CR-POPF rate was 12.3%. Fistula risk score (FRS) was the only significant risk factor for the occurrence of overall POPF in multivariate analysis. However, none of the other factors including FRS was found to be significantly associated with CR-POPF risk. A strong positive correlation was found between the CR-POPF and the incidence of delayed gastric emptying, post-pancreatectomy hemorrhage and increased length of hospital stay. Conclusion: Blumgart’s technique is a safe technique of pancreatico-enteric anastomosis with low rates of CR-POPF. CR-POPF with this technique is independent of most of the preoperative and intraoperative factors. Therefore, this technique can be used for all types of the pancreas with consistently good results.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 181-187 . [Abstract] ( 60 ) [HTML 1KB] [PDF 0KB] ( 108 )

	188	Mahendran R, Tewari M, Dixit VK, Shukla HS
		Enhanced recovery after surgery protocol enhances early postoperative recovery after pancreaticoduodenectomy
		Background: Enhanced recovery after surgery (ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy (PD). Methods: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube (NGT) was removed on postoperative day (POD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on POD2; semisolid diet by POD3; abdominal drain was removed on POD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula (POPF); normal diet was allowed on POD5. Discharge criteria on POD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications (defined as per the ISGPS definitions). Results: NGT was removed on POD1 in 45 (90%) patients, abdominal drain removed by POD4 in 41 (82%) and 43 (86%) patients were discharged on POD6. There was no 30-day postoperative mortality. Three (6%) patients had delayed gastric emptying (DGE). None had postoperative hemorrhage and POPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay (LOS) with age ( P < 0.05) and a marginal relation between LOS and postoperative albumin ( P = 0.05). Conclusions: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LOS and postoperative complications.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 188-193 . [Abstract] ( 64 ) [HTML 1KB] [PDF 0KB] ( 143 )

LETTERS TO THE EDITOR

	194	Mao JX, Teng F, Yuan H, Liu C, Fu H, Sun KY, Ding GS, Guo WY
		Primary hepatic squamous cell carcinoma with abdominal incision metastasis after hepatectomy
		Primary hepatic squamous cell carcinoma (PHSCC) is a rare and easily misdiagnosed disease. We reported a PHSCC case with abdominal incision metastasis after hepatectomy, and reviewed the clinical course, imaging, pathology and immunohistochemical findings. Our case may provide a better understanding of PHSCC.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 194-198 . [Abstract] ( 67 ) [HTML 1KB] [PDF 0KB] ( 123 )

	199	Losurdo G, Ingravallo G, Mongelli A, Castellaneta NM, Pisani A
		Unexpected mediastinal mass in a liver transplanted patient
		The risk of de novo cancer increases by 2 to 7-fold after liver transplantation [1] . The most common de novo cancers are both solid (non-melanoma skin cancers, colorectal carcinoma, genito-urinary and head-neck cancer) [2,3] as well as hematologic malignancies, in particular the so-called post-transplant lymphoproliferative disorder [4] . Immunosuppressive regimen could be the most important cause for increased cancer risk, since currently used drugs lead to a chronic impairment of immune-surveillance against cancer, thus promoting proliferation and survival of malignant cellular clones [5] . Recurrence of hepatocellular carcinoma (HCC) in patients transplanted for HCC within Milan criteria is another aspect of the oncologic scenario related to post-transplant period. Indeed, about 10% of liver recipients experience HCC recurrence, and this event is associated to male gender, size of HCC, vascular invasion and viral hepatitis [6] . We report a case who developed a mediastinal solid malignancy 7 years after liver transplantation.
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 199-201 . [Abstract] ( 46 ) [HTML 1KB] [PDF 0KB] ( 114 )

	202	Han J, Yan WT, Quan B, Wang MD, Yang T
		Statins, diabetes, obesity, nonalcoholic fatty liver disease, and hepatocellular carcinoma
		We read with great interest the recent article by Chang et al. [1] . By analyzing the data of 1350 cirrhotic patients, the authors concluded that statin significantly decreases the risk of decompensation of cirrhosis, mortality and hepatocellular carcinoma (HCC) incidence, and these effects are dose dependent. Herein, we would like to comment as followings:
		Hepatobiliary Pancreat Dis Int. 2019; 18(2): 202-202 . [Abstract] ( 47 ) [HTML 1KB] [PDF 0KB] ( 111 )

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