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Eastliver
  Hepatobiliary Pancreat Dis Int
 
2018 Vol.  17 No.  2
Published: 2018-04-15

pages 93-181
EDITORIAL
META-ANALYSIS
REVIEW ARTICLES
ORIGINAL ARTICLES/Transplantation
ORIGINAL ARTICLES/Liver
ORIGINAL ARTICLES/Biliary
ORIGINAL ARTICLES/Pancreas
LETTERS TO THE EDITOR
EDITORIAL
93 Yang HY, Sun LJ, Mao YL
Combination of tumor-associated regulatory T cell deletion and PD-1/PD-L1 blockade: A promising immunotherapy for hepatocellular carcinoma?
During the past decades, the treatment of hepatocellular carcinoma (HCC) has been limited to surgical resection and liver transplantation, but the prognosis is still poor. Recently, tumor immunotherapy, particularly immune checkpoints programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) blockade, brings a breakthrough for HCC [1,2]. However, anti-PD-1/PD-L1 immunotherapy is not satisfactory and the response rates were between 20% and 30% [3]. How to improve the efficacy of PD-1/PD-L1 blockade is the main issue.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 93-94 .
[Abstract] ( 136 ) [HTML 1KB] [PDF 0KB] ( 175 )
META-ANALYSIS
95 Gao HL, Liu L, Qi ZH, Xu HX, Wang WQ, Wu CT, Zhang SR, Xu JZ, Ni QX, Yu XJ
The clinicopathological and prognostic significance of PD-L1 expression in pancreatic cancer: A meta-analysis
BACKGROUND: Immunotherapy has shown promise against solid tumors. However, the clinical significance of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This meta-analysis aimed to analyze the prognostic effect of PD-L1 in PDAC.
DATA SOURCES: Electronic search of the PubMed, Cochrane Library and Web of Science was performed until December 2016. Through database searches, we identified articles describing the relationship between PD-L1 status and PDAC patient prognosis. Meta-analysis was performed to investigate the relationship between PD-1 and overall survival (OS).
RESULTS: Nine studies with 989 PDAC patients were included for PD-L1 expression analysis. And 5 studies with 688 PDAC patients were included in the prognostic analysis. The PD-L1 positive rate measured by immunohistochemistry (IHC) was higher than that measured by polymerase chain reaction (PCR) (P?<?0.001). PDAC patients with high expression levels of PD-L1 had significantly reduced OS (HR?=?2.34; 95% CI: 1.78-3.08). Subgroup analysis showed that the prognostic effect of PD-L1 levels was similar between the IHC and PCR methods. The PD-L1 positive rate was associated with PDAC T stages; the PD-L1 positive rate in the T3-4 group was higher than that in the T1-2 group (OR?=?0.37; P?=?0.001).
CONCLUSIONS: High PD-L1 expression levels predicted a poor prognosis in PDAC patients. Thus, PD-L1 status helps determine treatment in PDAC patients.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 95-100 .
[Abstract] ( 166 ) [HTML 1KB] [PDF 0KB] ( 170 )
REVIEW ARTICLES
101 Tang R, Ma LF, Rong ZX, Li MD, Zeng JP, Wang XD, Liao HE, Dong JH
Augmented reality technology for preoperative planning and intraoperative navigation during hepatobiliary surgery: A review of current methods Hot!
BACKGROUND: Augmented reality (AR) technology is used to reconstruct three-dimensional (3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes.
DATA SOURCES: The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were used for searching publications in the PubMed database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles.
RESULTS: In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery, which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology.
CONCLUSIONS: With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling, and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 101-112 .
[Abstract] ( 175 ) [HTML 1KB] [PDF 0KB] ( 172 )
113 Khoury J, Zohar Y, Shehadeh N, Saadi T
Glycogenic hepatopathy
BACKGROUND: Glycogenic hepatopathy (GH) is a disorder associated with uncontrolled diabetes mellitus, most commonly type 1, expressed as right upper quadrant abdominal pain, hepatomegaly and increased liver enzymes. The diagnosis may be difficult, because laboratory and imaging tests are not pathognomonic. Although GH may be suggested based on clinical presentation and imaging studies, the gold standard for diagnosis is a liver biopsy, showing a significant accumulation of glycogen within the hepatocytes. GH may be diagnosed also after elevated liver enzymes in routine blood tests. GH usually regresses after tight glycemic control. Progression to end-stage liver disease has never been reported. This review aims to increase the awareness to this disease, to suggest a pathway for investigation that may reduce the use of unnecessary tests, especially invasive ones.
DATA SOURCES: A PubMed database search (up to July 1, 2017) was done with the words "glycogenic hepatopathy", "hepatic glycogenosis", "liver glycogenosis" and "diabetes mellitus-associated glycogen storage hepatopathy". Articles in which diabetes mellitus-associated liver glycogen accumulation was described were included in this review.
RESULTS: A total of 47 articles were found, describing 126 patients with GH. Hepatocellular disturbance was more profound than cholestatic disturbance. No synthetic failure was reported.
CONCLUSIONS: GH may be diagnosed conservatively, based on corroborating medical history, physical examination, laboratory tests, imaging studies and response to treatment, even without liver biopsy. In case of doubt about the diagnosis or lack of clinical response to treatment, a liver biopsy may be considered. There is no role for noninvasive tests like fibroscan or fibrotest for the diagnosis of GH or for differentiation of this situation from nonalcoholic fatty liver disease.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 113-118 .
[Abstract] ( 161 ) [HTML 1KB] [PDF 0KB] ( 155 )
ORIGINAL ARTICLES/Transplantation
119 Lee EC, Kim SH, Shim JR, Park SJ
A comparison of desensitization methods: Rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation Hot!
BACKGROUND: Plasmapheresis is a desensitization method used prior to ABO-incompatible (ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.
METHODS: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January 2012 and October 2015. A single dose of rituximab (300 mg/m2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014 (RP group, n=26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015 (RO group, n=30).
RESULTS: The 6-, 12- and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively (P=0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.
CONCLUSIONS: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 119-125 .
[Abstract] ( 182 ) [HTML 1KB] [PDF 0KB] ( 195 )
ORIGINAL ARTICLES/Liver
126 Wen Y, Peng SF, Fu L, Fu XY, Wu DX, Liu BJ, Tan DM, Ouyang Y
Serum levels of miRNA in patients with hepatitis B virus-associated acute-on-chronic liver failure
BACKGROUND: Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum miRNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF.
METHODS: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to 30 chronic asymptomatic HBV carriers as controls. The miRNAs expressions were measured by real-time quantitative PCR (q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed miRNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model.
RESULTS: Real-time q-PCR indicated that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and miR-122-3p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+ - 1.72 × INR - 4.963 × gastrointestinal bleeding (Yes = 0; No = 1)-0.278×(miR-122-3p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve (AUROC) was 0.847.
CONCLUSIONS: Expression levels of these miRNAs (miR-146a-5p, miR-122-3p and miR-328-3p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 126-132 .
[Abstract] ( 157 ) [HTML 1KB] [PDF 0KB] ( 184 )
133 Qu LM, Wang SH, Yang K, Brigstock DR, Sun L, Gao RP
CD4+Foxp3+CD25+/- Tregs characterize liver tissue specimens of patients suffering from drug-induced autoimmune hepatitis: A clinical-pathological study
BACKGROUND: The diagnosis of drug-induced autoimmune hepatitis (DIAIH) and its differentiation from idiopathic autoimmune hepatitis (AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4+Foxp3+CD25+/- regulatory T cells (Tregs) in liver tissues or peripheral blood lymphocytes.
METHODS: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4+Foxp3+CD25+/- Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4+Foxp3+CD25+/-Tregs in peripheral blood were analyzed by flow cytometry.
RESULTS: The median values of ALT and AST were 404.50?U/L and 454.10 U/L in DIAIH patients and 309.50?U/L and 315.00?U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation, higher frequencies of zone 3 necrosis and higher number of lobular CD4+Foxp3+CD25-Tregs compared with AIH (P<0.05). Furthermore, there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4+Foxp3+CD25- Tregs (P<0.05). However, the frequency of peripheral blood CD4+Foxp3+CD25+/- Tregs were not significantly different between DIAIH and AIH.
CONCLUSIONS: The differences of ALT, AST and the number of lobular CD4+Foxp3+CD25- Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 133-139 .
[Abstract] ( 129 ) [HTML 1KB] [PDF 0KB] ( 158 )
140 Xu HL, Li M, Zhang RJ, Jiang HJ, Zhang MY, Li X, Wang YQ, Pan WB
Prediction of tumor biological characteristics in different colorectal cancer liver metastasis animal models using 18F-FDG and 18F-FLT
BACKGROUND: Positron emission tomography (PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of 18F-fludeoxyglucose (18F-FDG) and 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.
METHODS: The uptake rate of 18F-FDG and 18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio (tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.
RESULTS: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of 18F-FDG in SW480 and SW620 cells was 6.07%?±?1.19% and 2.82%?±?0.15%, respectively (t?=?4.69, P?=?0.04); that of18F-FLT was 24.81%?±?0.45% and 15.57%?±?0.66%, respectively (t?=?19.99, P?<?0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and 18F-FLT uptake in primary tumors (r?=?0.73, P?=?0.0019). 18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases (r?=?0.81, P?=?0.0049).
CONCLUSIONS: The uptake of 18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells. 18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 140-148 .
[Abstract] ( 153 ) [HTML 1KB] [PDF 0KB] ( 185 )
ORIGINAL ARTICLES/Biliary
149 Goussous N, Maqsood H, Patel K, Ferdosi H, Muhammad N, Sill AM, Kowdley GC, Cunningham SC
Clues to predict incidental gallbladder cancer
BACKGROUND: Consequences of incidental gallbladder cancer (iGBC) following cholecystectomy may include repeat operation (depending on T stage) and worse survival (if bile spillage occurred), both avoidable if iGBC were suspected preoperatively.
METHODS: A retrospective single-institution review was done. Ultrasound images for cases and controls were blindly reviewed by a radiologist. Chi-square and Student's t tests, as well as logistic regression and Kaplan-Meier analyses were used. A P?≤?0.01 was considered significant.
RESULTS: Among 5796 cholecystectomies performed 2000-2013, 26 (0.45%) were iGBC cases. These patients were older (75.61 versus 52.27 years), had more laparoscopic-to-open conversions (23.1% versus 3.9%), underwent more imaging tests, had larger common bile duct diameter (7.13 versus 5.04?mm) and higher alkaline phosphatase. Ultrasound imaging showed that gallbladder wall thickening (GBWT) without pericholecystic fluid (PCCF), but not focal-versus-diffuse GBWT, was associated significantly with iGBC (73.9% versus 47.4%). On multivariable logistic regression analysis, GBWT without PCCF, and age were the strongest predictors of iGBC. The consequences iGBC depended significantly on intraoperative bile spillage, with nearly all such patients developing carcinomatosis and significantly worse survival.
CONCLUSIONS: Besides age, GBWT, dilated common bile duct, and elevated alkaline phosphatase, number of preoperative imaging modalities and the presence of GBWT without PCCF are useful predictors of iGBC. Bile spillage causes poor survival in patients with iGBC.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 149-154 .
[Abstract] ( 146 ) [HTML 1KB] [PDF 0KB] ( 154 )
155 Chen KJ, Yang FC, Qin YS, Jin J, Zheng SS
Assessment of clinical outcomes of advanced hilar cholangiocarcinoma
BACKGROUND: Low resectability and poor survival outcome are common for hilar cholangiocarcinoma (HCCA), especially in advanced stages. The present study was to assess the clinical outcome of advanced HCCA, focusing on therapeutic modalities, survival analysis and prognostic assessment.
METHODS: Clinical data of 176 advanced HCCA patients who had been treated in our hospital between January 2013 and December 2015 were analyzed retrospectively. Prognostic effects of clinicopathological factors were explored by univariate and multivariate analysis. Survival predictors were evaluated by the receiver operating characteristic (ROC) curve.
RESULTS: The 3-year overall survival rate was 13% for patients with advanced HCCA. Preoperative total bilirubin (P?=?0.009), hepatic artery invasion (P?=?0.014) and treatment modalities (P?=?0.020) were independent prognostic factors on overall survival. A model combining these independent prognostic factors (area under ROC curve: 0.748; 95% CI: 0.678-0.811; sensitivity: 82.3%, specificity: 53.5%) was highly predictive of tumor death. After R0 resection, the 3-year overall survival was up to 38%. Preoperative total bilirubin was still an independent negative factor, but not for hepatic artery invasion.
CONCLUSIONS: Surgery is still the best treatment for advanced HCCA. Preoperative biliary drainage should be performed in highly-jaundiced patients to improve survival. Prediction of survival is improved significantly by a model that incorporates preoperative total bilirubin, hepatic artery invasion and treatment modalities.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 155-162 .
[Abstract] ( 143 ) [HTML 1KB] [PDF 0KB] ( 155 )
ORIGINAL ARTICLES/Pancreas
163 Li B, Xu C, Qiu ZQ, Liu C, Yi B, Luo XJ, Jiang XQ
An end-to-side suspender pancreaticojejunostomy: A new invagination pancreaticojejunostomy
BACKGROUND: Postoperative pancreatic fistula (POPF) is a severe complication of the pancreaticoduodenectomy (PD). Recently, we introduced a method of suspender pancreaticojejunostomy (PJ) to the PD. In this study, we retrospectively analyzed various risk factors for complications after PD. We also introduced and assessed the suspender PJ to demonstrate its advantages.
METHODS: Data from 335 patients with various periampullary lesions, who underwent the Whipple procedure (classic Whipple procedure or pylorus-preserving) PD by either traditional end-to-side invagination PJ or suspender PJ, were analyzed. The correlation between either perioperative or postoperative complications and corresponding PD approaches was evaluated by univariate analysis.
RESULTS: A total of 147 patients received the traditional end-to-side invagination PJ, and 188 patients were given the suspender PJ. Overall, 51.9% patients had various complications after PD. The mortality rate was 2.4%. The POPF incidence in patients who received the suspender PJ was 5.3%, which was significantly lower than those who received the traditional end-to-side invagination PJ (18.4%) (P?<?0.001). Univariate analysis showed that PJ approach and the pancreas texture were significantly associated with the POPF incidence rate (P?<?0.01). POPF was a risk factor for both postoperative abdominal cavity infection (OR?=?8.34, 95% CI: 3.99-17.42, P?<?0.001) and abdominal cavity hemorrhage (OR?=?4.86, 95% CI: 1.92-12.33, P?=?0.001).
CONCLUSIONS: Our study showed that the impact of the pancreas texture was a major risk factor for pancreatic leakage after a PD. The suspender PJ can be easily accomplished and widely applied and can effectively decrease the impact of the pancreas texture on pancreatic fistula after a PD and leads to a lower POPF incidence rate.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 163-168 .
[Abstract] ( 145 ) [HTML 1KB] [PDF 0KB] ( 194 )
169 Benetatos N, Hodson J, Marudanayagam R, Sutcliffe RP, Isaac JR, Ayuk J, Shah T, Roberts KJ
Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems Hot!
BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) display wide heterogeneity with highly variable prognosis. This study aimed to identify variables related to survival after surgical resection of PNET.
METHODS: A total of 143 patients were identified from a prospectively maintained database. Patient characteristics were analyzed and prognostic factors for overall survival and progression-free survival were evaluated. The WHO, ENETS and AJCC scoring systems were applied to the cohort, and their ability to predict patient outcomes were compared.
RESULTS: Multivariate analysis found that female gender, lymph node metastases and increasing WHO 2010 grade to be independently associated with reduced overall survival (P?<?0.05). Patients requiring multi-visceral resection or debulking surgery found to be associated with shortest survival. ROC analysis found the ENETS and AJCC scoring systems to be similarly predictive of 5-year overall survival. Modified Ki67 significantly improved its accuracy in predicting 5-year overall survival (AUROC: 0.699 vs 0.605; P?<?0.01).
CONCLUSIONS: Multi-visceral or debulking surgery is associated with poor outcomes. There seems to be no significant difference between enucleation and anatomical segmental resection. Available scoring systems have reasonable accuracy in stratifying disease severity, with no system identified as being superior. Prognostic stratification with modified grading systems needs further validation before applied in clinical practice.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 169-175 .
[Abstract] ( 190 ) [HTML 1KB] [PDF 0KB] ( 167 )
LETTERS TO THE EDITOR
176 Srinivasa RN, Srinivasa RN, Gemmete JJ, Chick JFB
Bugbee flexible electrocautery facilitates choledochoscopic biopsy, fulguration, and debulking of a high grade intraductal papillary neoplasm of the bile duct
To the Editor:
Intraductal papillary neoplasm of the bile duct (IPNB) may occur in the setting of primary sclerosing cholangitis, choledochal cysts or hepatolithiasis [1]. The entity may be a precursor of cancer or intrahepatic cholangiocarcinoma. Invasive carcinoma, tubular or mucinous adenocarcinoma is present in approximately 40%−80% of IPNBs [1–3]. IPNB is frequently found in the resection margins of patients undergoing hepatectomy for cholangiocarcinoma [4]. This report describes a patient with obstructive jaundice secondary to IPNB who underwent interventional radiology-operated choledochoscopic-guided flexible electrocautery and fulguration to facilitate diagnostic biopsy and debulking of intrabiliary tumor.
Hepatobiliary Pancreat Dis Int. 2018; 17(2): 176-179 .
[Abstract] ( 126 ) [HTML 1KB] [PDF 0KB] ( 173 )

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