Hepatobiliary Pancreat Dis Int

	2020 Vol. 19 No. 3
	Published: 2020-06-15


	Pages 203-304
	EDITORIAL REVIEW ARTICLES ORIGINAL ARTICLES/Transplantation ORIGINAL ARTICLES/Liver ORIGINAL ARTICLES/Biliary ORIGINAL ARTICLES/Pancreas CLINICAL IMAGE LETTERS TO THE EDITOR VIEWPOINTS

EDITORIAL

	203	Jin LM, Zhang YH, Zhang CW, Wu WD, Wu J, Dou CW, Wei FQ, Wang ZF, Hu ZM, Zheng SS
		Is laparoscopic radical cholecystectomy an effective and safe approach for advanced gallbladder cancer?
		Although laparoscopy has been widely used in the surgical field and is even considered the first-line to diagnose various diseases, laparoscopic radical cholecystectomy (LRC) for gallbladder cancer (GBC) has always been relatively contraindicated. Inadequate lymphadenectomy, complicated liver resection, specific biological behavior of GBC cells, and chimney and aerosol effects from the pneumoperitoneum are the previously misunderstood areas in laparoscopic surgery [1] . Initially, laparoscopic approach was used for intra-abdominal GBC exploration to determine the presence of peritoneal metastasis, intraoperative staging, and palliative treatment. With the advancement of laparoscopic surgery, laparoscopic liver resection, laparoscopic pancreaticoduodenectomy, and laparoscopic radical gastrectomy have been routinely performed in several medical centers. Kim et al. [2] recently demonstrated that laparoscopic technique is feasible for GBC. However, the feasibility of LRC depends on the following factors.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 203-204 . [Abstract] ( 109 ) [HTML 1KB] [PDF 0KB] ( 134 )

REVIEW ARTICLES

	205	Bararia A, Dey S, Gulati S, Ghatak S, Ghosh S, Banerjee S, Sikdar N
		Differential methylation landscape of pancreatic ductal adenocarcinoma and its precancerous lesions ^Hot!
		Background: Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality. In addition to having genetic causes, cancer can also be considered an epigenetic disease. DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recog- nized to be a common hallmark of human tumor. In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma (PDAC), the epigenetic changes play a significant role. Data sources: Relevant studies for this review were derived via an extensive literature search in PubMed via using various keywords such as pancreatic ductal adenocarcinoma, precancerous lesions, methylation profile, epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest. The literature search was intensively done considering a time frame of 20 years (1998–2018). Result: In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions (pancreatic intra-epithelial neoplasia, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm and chronic pancreatitis) and PDAC along with the potential biomarkers. We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC. A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC ( ppENK, APC, p14/5/16/17, hMLH1 and MGMT ) are also documented. We summarized the importance of these observa- tions in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy. Epigenetic inactivation occurs by hypermethylation of CpG islands in the promoter regions of tumor suppressor genes. We listed all hyper- and hypomethylation of CpG islands of several genes in PDAC including its precancerous lesions. Conclusions: The concept of the review would help to understand their biological effects, and to determine whether they may be successfully combined with other epigenetic drugs. However, we need to continue our research to develop more specific DNA-demethylating agents, which are the targets for hy- permethylated CpG methylation sites.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 205-217 . [Abstract] ( 94 ) [HTML 1KB] [PDF 0KB] ( 166 )

	218	Hu ZQ, Lu Y, Cui D, Ma CY, Shao S, Chen P, Tao R, Wang JJ
		MicroRNAs and long non-coding RNAs in liver surgery: Diagnostic and therapeutic merits
		Background: Hepatectomy and liver transplantation (LT) are the two most commonly performed surgical procedures for various hepatic lesions. microRNA (miRNA) and long non-coding RNA (lncRNA) have been gradually unveiled their roles as either biomarkers for early diagnosis or potentially therapeutic tools to manipulate gene expression in many disease entities. This review aimed to discuss the effects of miRNA or lncRNA in the hepatectomy and LT fields. Data sources: We did a literature search from 1990 through January 2018 to summarize the currently available evidence with respect to the effects of miRNA and lncRNA in liver regeneration after partial hep- atectomy, as well as their involvement in several key issues related to LT, including ischemia-reperfusion injury, allograft rejection, tolerance, recurrence of original hepatic malignancies, etc. Results: Certain miRNAs and lncRNAs are actively involved in the regulation of various aspects of liver resection and transplantation. During the process of liver regeneration after hepatectomy, the expression of miRNAs and lncRNAs shows dynamic changes. Conclusions: It is now clear that miRNAs and lncRNAs orchestrate in various aspects of the pathophys- iological process of LT and hepatectomy. Better understanding of the underlying mechanism and future clinical trials may strengthen their positions as either biomarkers or potential therapeutic targets in the management of complications after liver surgery.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 218-228 . [Abstract] ( 112 ) [HTML 1KB] [PDF 0KB] ( 178 )

ORIGINAL ARTICLES/Transplantation

	229	Yang Z, Luo FZ, Wang S, Lerut J, Zhuang L, Li QY, Xu X, Zheng SS
		Alpha-fetoprotein and 18 F-FDG standard uptake value predict tumor recurrence after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis: Preliminary experience ^Hot!
		Background: Portal vein tumor thrombosis (PVTT) is regarded as a contraindication for liver transplantation (LT) in hepatocellular carcinoma (HCC). However, some of these patients may have a favorable prognosis after LT. In this study, we evaluated the biological behavior of HCC with PVTT using tumor biomarker (alpha-fetoprotein, AFP) and 18 F-FDG positron emission tomography (tumor standard uptake value) to identify a subset of patients who may be suitable for LT. Methods: Seventy-five HCC-PVTT liver recipients transplanted during February 2016 and June 2018 were analyzed. Different pre-transplant prognostic factors were identified by univariate and multivariate analyses. PVTT status was identified following Vp classification (Vp1-Vp4). Results: Three-year recurrence-free survival and overall survival rates were 40% and 65.4% in Vp2-Vp3 PVTT patients, 21.4% and 30.6% in Vp4 PVTT patients ( P < 0.05). Total tumor diameter > 8 cm, pre- transplant AFP level > 10 0 0 ng/mL and intrahepatic tumor maximal standard uptake value (SUVmax-tumor > 5) were independent risk factors for HCC recurrence and overall survival after LT in Vp2-3 PVTT patients. Low risk patients were defined as total tumor diameter ≤8 cm; or if total tumor diameter more than 8 cm, with both pre-transplant AFP level less than 10 0 0 ng/mL and intrahepatic tumor SUVmax less than 5, simultaneously. Twenty-two Vp2-3 PVTT HCC patients (46.8%) were identified as low risk patients, and their 3-year recurrence-free and overall survival rates were 67.6% and 95.2%, respectively. Conclusions: Patients with segmental or lobar PVTT and biologically favorable tumors defined by AFP and 18 F-FDG SUVmax might be suitable for LT.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 229-234 . [Abstract] ( 112 ) [HTML 1KB] [PDF 0KB] ( 158 )

	235	Lin ZB, Yang PJ, Zhang X, Wang JL, Liu K, Dou KF
		Translationally controlled tumor protein exerts a proinflammatory role in acute rejection after liver transplantation
		Background: Translationally controlled tumor protein (TCTP), which has been verified to have a proinflammatory activity, plays an important role in allergy. However, it remains unclear whether TCTP has an impact on the acute rejection (AR) after liver transplantation. Methods: Three protocols were used to delineate the role of TCTP in AR after liver transplantation. First, in rat orthotopic liver transplantation (OLT), the expression of TCTP was measured by enzyme-linked immunosorbent assay (ELISA), real-time PCR, Western blot and immunofluorescence assays. Second, in mixed lymphocyte reaction (MLR), the role of TCTP in lymphocyte proliferation was measured by carboxyfluorescein succinimidyl ester (CFSE) labeling and the impact of TCTP on inflammatory factor release was detected by cytokine arrays. Third, in human OLT, the level of serum TCTP was detected by ELISA, and the relationship between TCTP and model for early allograft function (MEAF) score was assessed by Spearman’s correlation. Results: In rat OLT, AR resulted in great harm to allografts, manifesting as deterioration of liver function, increasing inflammatory factors and infiltrating lymphocytes. Meanwhile, TCTP was overexpressed in serum and allografts. Higher level of TCTP was associated with higher rejection activity index (RAI). In an MLR protocol, TCTP knockdown inhibited the proliferation of mixed inflammatory cells and significantly suppressed the release of 15 cytokines and chemokines. In human OLT, the serum TCTP was up-regulated within a week after operation. Additionally, the increasing speed of serum TCTP positively correlated with MEAF scores ( r = 0.449; P = 0.0088). Conclusions: Up-regulated TCTP positively affects AR after liver transplantation.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 235-243 . [Abstract] ( 101 ) [HTML 1KB] [PDF 0KB] ( 170 )

ORIGINAL ARTICLES/Liver

	244	Park GC, Lee SG, Yoon YI, Sung KB, Ko GY, Gwon DI, Jung DH, Jung YK
		Sequential transcatheter arterial chemoembolization and portal vein embolization before right hemihepatectomy in patients with hepatocellular carcinoma ^Hot!
		Background: Recent studies showed that sequential selective transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) provided better future liver remnant (FLR) regeneration rate and disease-free survival following surgery compared with PVE alone. The present study aimed to clarify whether preoperative sequential TACE and PVE before right hemihepatectomy can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve long-term disease-free and overall survival. Methods: Recurrence and survival outcomes were retrospectively evaluated in 205 patients with HCC who underwent right hemihepatectomy by a single surgeon from November 1993 to November 2017. Patients were divided into four groups according to the procedure performed before the surgery: sequential TACE and PVE (TACE-PVE), PVE-only, TACE-only, or naïve control groups. The baseline patient and tumor characteristics, postoperative outcomes, recurrence-free survival and overall survival were analyzed. Results: Baseline patient and tumor characteristics upon diagnosis were similar in all four groups, while sequential TACE and PVE were well tolerated. The TACE-PVE group had a higher mean increase in percentage FLR volume compared with that of the PVE-only group (17.46% ± 6.63% vs. 12.14% ± 5.93%; P = 0.001). The TACE-PVE group had significantly better overall and disease-free survival rates compared with the other groups (both P < 0.001). Conclusions: Sequential TACE and PVE prior to surgery can be an effective therapeutic strategy for patients with HCC scheduled for major hepatic resection. The active application of preoperative sequential TACE and PVE for HCC would allow more patients with marginal FLR volume to become candidates for major hepatic resection by promoting compensatory FLR hypertrophy without the deterioration of basal hepatic functional reserve or tumor progression.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 244-251 . [Abstract] ( 99 ) [HTML 1KB] [PDF 0KB] ( 156 )

	252	Wu LM, He H, Chen G, Kuang Y, Lin BY, Chen XH, Zheng SS
		Associations between obesity and metabolic health with nonalcoholic fatty liver disease in elderly Chinese
		Background: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. However, this association could be influenced by the coexisting metabolic abnormalities. This study aimed to investigate the role of obesity and metabolic abnormalities in NAFLD among elderly Chinese. Methods: A cross-sectional study was performed among elderly residents who took their annual health checkups during 2016 in Keqiao District, Shaoxing, China. Results: A total of 3359 elderly adults were retrospectively included in this study. The overall prevalence of NAFLD was 28.7%. The prevalence of NAFLD were 7.14%, 27.92%, 34.80%, and 61.02% in participants with metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabol- ically healthy obese (MHO), and metabolically abnormal obese (MAO), respectively. NAFLD patients in MHO group had more unfavorable metabolic profiles than those in MHNW group. Logistic regression analysis showed that sex, body mass index (BMI), fasting blood glucose, and serum uric acid were the risk factors of NAFLD. Conclusions: Both obesity and metabolic health were significantly associated with NAFLD in elderly Chinese. Screening for obesity and other metabolic abnormalities should be routinely performed for early risk stratification of NAFLD.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 252-257 . [Abstract] ( 98 ) [HTML 1KB] [PDF 0KB] ( 154 )

	258	Hashim Z, Ilyas A, Zarina S
		Therapeutic effect of hydrogen peroxide via altered expression of glutathione S-transferase and peroxiredoxin-2 in hepatocellular carcinoma
		Background: Hepatocellular carcinoma (HCC) has a high incidence and mortality that epitomizes one of the prominent causes of cancer-related death globally. Novel therapeutic approaches are therefore required. Reactive oxygen species (ROS) are necessary for maintaining cell cycle. Although ROS is involved in HCC progression, hydrogen peroxide (H2O2) has anti-proliferative effect on HCC. Method: HCC Huh-7 cells were cultured and incubated with various concentrations of H 2 O 2 . Paraoxonase activity, levels of malondialdehyde, glutathione and protein oxidation were measured in treated and untreated Huh-7 cells. Furthermore, untreated and treated Huh-7 cells were subjected to two dimensional gel electrophoresis and identified protein spots which were differentially expressed by LC-MS/MS analysis. qRT-PCR was performed to validate the identified proteins. Results: H2O2 depleted glutathione (GSH) with the concomitant up-regulation of GSTP1 and Prx2. H2O2 also increased malondialdehyde and protein oxidation, decreased the activity of paraoxonase in Huh-7 cells. Conclusion: H2O2 could be used as a novel therapeutic agent that might be beneficial in inducing cell cytotoxicity and hence suppress HCC proliferation.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 258-265 . [Abstract] ( 98 ) [HTML 1KB] [PDF 0KB] ( 158 )

ORIGINAL ARTICLES/Biliary

	266	Kadah A, Khoury T, Mahamid M, Assy N, Sbeit W
		Predicting common bile duct stones by non-invasive parameters
		Background: Common bile duct (CBD) stone affect about 10% of patients with symptomatic cholelithiasis. The American Society for Gastrointestinal Endoscopy (ASGE) published a strategy in 2010 for managing patients with suspected choledocholithiasis. This study aimed to assess the performance of different clinical parameters in predicting CBD stones. Methods: A total of 344 patients suspected to suffer from CBD stone and referred to endoscopic ultrasound (EUS) were included. Parameters were collected and their prediction power for CBD stones was assessed. Results: One hundred and sixty-seven patients without CBD stone according to EUS (group A) were com- pared to 177 patients with CBD stones (group B). Several predictive factors for CBD stone were identi- fied on univariate analysis. In multivariate regression analysis, CBD width by US (OR = 1.224, 95% CI: 1.073–1.359; P = 0.0026), age (OR = 1.023, 95% CI: 1.011–1.035; P = 0.0 0 02) and gamma glutamyl transferase (GGT) level (OR = 1.001, 95% CI: 1.000–1.002; P = 0.0018) were significantly correlated with CBD stone, with receiver operator characteristics (ROC) of 0.7259. We generated a diagnostic equation [age (yr) ×0.1 + CBD width (mm) by US ×1 + GGT (U/L) ×0.005] to predict CBD stone with ROC of 0.7287. Conclusions: We suggest this score as a very strong predictor for CBD stones, and to reduce the strength of total bilirubin and transaminases as predictors.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 266-270 . [Abstract] ( 106 ) [HTML 1KB] [PDF 0KB] ( 155 )

	271	Guler BG, Ozler S
		Increased syndecan-1 and glypican-3 predict poor perinatal outcome and treatment resistance in intrahepatic cholestasis
		Background: Intrahepatic cholestasis of pregnancy (ICP) increases the risk of adverse pregnancy outcomes. This study aimed to explore the association between serum syndecan-1 and glypican-3 levels and the adverse perinatal outcome as well as the responses to the treatment of ursodeoxycholic acid (UDCA). Methods: This prospective, case control study included 88 pregnant women (44 women with ICP and 44 healthy controls). The primary end points were the perinatal outcome and the response to UDCA therapy. A logistic regression model was used to identify the independent risk factors of adverse pregnancy outcomes and reduced response to UDCA therapy. Results: Women with ICP had significantly higher serum syndecan-1 (1.27 ± 0.36 ng/mL vs. 0.98 ± 0.50 ng/mL; P = 0.003), glypican-3 (1.78 ±0.13 ng/mL vs.1.69 ±0.16 ng/mL; P = 0.004), AST (128.59 ±1.44 vs. 13.29 ± 1.32 U/L; P < 0.001), and ALT (129.84 ± 1.53 vs. 8.00 ± 3.67 U/L; P < 0.001) levels compared with the controls. The increased levels of syndecan-1 (OR = 4.715, 95% CI: 1.554–14.310; P = 0.006), glypican-3 (OR = 8.465, 95% CI: 3.372–21.248; P = 0.007), ALT (OR = 1.382, 95% CI: 1.131–1.690; P = 0.002), and postprandial bile acid (PBA) (OR = 3.392, 95% CI: 1.003–12.869; P = 0.026) were correlated to ICP. The adverse neonatal outcome was related to increased glypican-3 (OR = 4.275, 95% CI: 2.726–5.635; P = 0.039), and PBA (OR = 3.026, 95% CI: 1.069–13.569; P = 0.037). Increases of syndecan- 1 (OR = 7.464, 95% CI: 2.130–26.153, P = 0.017) and glypican-3 (OR = 6.194, 95% CI: 2.951–13.002; P = 0.025) were the risk factors of decreased response to UDCA treatment. Conclusion: Syndecan-1 and glypican-3 might be powerful determinants in predicting adverse perinatal outcome in patients with ICP, and they can be used to predict the response to the UDCA treatment.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 271-276 . [Abstract] ( 96 ) [HTML 1KB] [PDF 0KB] ( 154 )

ORIGINAL ARTICLES/Pancreas

	277	Zeng ZL, Sun Y, Xue D, Liu PL, Chen WM, Zhang L
		Effect of six-stitch pancreaticojejunostomy on pancreatic fistula: A propensity score-matched comparative cohort study
		Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common and severe complication after pancreaticoduodenectomy (PD). Despite the development of numerous anastomotic surgical techniques to minimize CR-POPF, more than 30% of patients who undergo PD develop CR-POPF. Herein, we propose a novel pancreaticojejunostomy (PJ) technique and evaluate its efficacy and safety compared to traditional PJ. Methods: This retrospective study enrolled 164 consecutive patients who underwent PJ after PD between January 2012 and June 2017. Of them, 78 (47.6%) underwent traditional PJ and 86 (52.4%) underwent six- stitch PJ. The primary outcome was CR-POPF at 1-month follow-up defined according to the revised 2016 International Study Group on Pancreatic Fistula definition. To adjust for baseline differences and selection bias, patients were matched by propensity scores, which left 63 patients with traditional PJ and 63 with six-stitch PJ. Results: Compared to patients who underwent traditional PJ (mean age 56.2 ± 9.4 years), patients who underwent six-stitch PJ (mean age 57.4 ± 11.4 years) had a lower CR-POPF rate. The risk of CR-POPF among patients who underwent six-stitch PJ was decreased by 81.7% after adjustment for age, sex, body mass index, and disease severity compared to patients who underwent traditional PJ. Additionally, the surgery time was reduced from 29 min for traditional PJ to 15 min for six-stitch PJ ( P < 0.001). Adverse effects such as abdominal fluid collection, abdominal bleeding, and wound infection were similar between two groups. Conclusion: Six-stitch PJ may be an effective and efficient PJ technique for patients who undergo PD surgery.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 277-283 . [Abstract] ( 104 ) [HTML 1KB] [PDF 0KB] ( 152 )

CLINICAL IMAGE

	284	Tian SY, Xu D, Wang YJ, Yu YH, Yang Y, Jiang TA
		Diagnostic value of contrast-enhanced ultrasonography for intrahepatic cholangiocarcinoma with tumor diameter larger than 5 cm
		Herein we reported 5 patients of mass-type intrahepatic cholangiocarcinoma (ICC) misdiagnosed as liver abscess by contrast-enhanced CT, the diagnosis was confirmed through contrast-enhanced ultrasound (CEUS) imaging and pathology.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 284-287 . [Abstract] ( 108 ) [HTML 1KB] [PDF 0KB] ( 165 )

	288	Liu ZX,Zhu JQ, Ma J, Kou JT, Li XL, He Q
		Deceased donor liver transplantation for Budd–Chiari syndrome: Long-segmental thrombosis of the inferior vena cava with extensive collateral circulation
		Budd–Chiari syndrome (BCS) is an infrequent clinical disease resulting from obstruction of the hepatic venous outflow tract anywhere from small hepatic veins to the inferior vena cava (IVC) [1] . Currently, step-wise treatment strategy has been proposed and widely adopted based on the patient’s status, which contains anticoagulation, thrombolysis, percutaneous recanalization, transjugular intrahepatic portosystemic shunt (TIPS) and surgical shunt [2] . It has been reported that up to 10%−20% of BCS patients still develop into liver function failure after the step-wise treatment [3] . Therefore, liver transplantation is the remaining rescue treatment in these patients. The five-year survival rate of BCS patients who underwent liver transplantation can reach as high as 80% [4,5] . Notably, very few BCS patients have been reported to have a long-segmental thrombus of IVC. Herein, we presented a patient with total obstruction of the IVC blocked by a longsegmental thrombus, where the common iliac veins and the renal veins were drained into the superior vena cava smoothly through collateral circulation.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 288-290 . [Abstract] ( 90 ) [HTML 1KB] [PDF 0KB] ( 154 )

VIEWPOINTS

	291	Zhu Y, Li ZY, Wang CG, Fang ZP, Jia WD, Zhang FB
		Laparoscopic combined with thoracoscopic transdiaphragmatic hepatectomy for hepatitis B-related hepatocellular carcinoma located in segment VII or VIII
		Laparoscopic hepatectomy (LH) is considered a safe and effective method of treating liver cancer because of its relatively low level of trauma, bleeding, pain, and short hospital stay as compared with traditional open surgery [1] . However, this is not ideal for tumors located in segment VII or VIII of the liver as these tumors are difficult to be exposed during laparoscopy, and the conversion rate is relatively high [2] . Although it has been reported that the thoracoscopic transdiaphragmatic segment VII or VIII hepatectomy can obtain better visual field and operation space [3] , it is difficult to control the bleeding of surgical wound. The application is therefore limited. To resolve this problem, we employed a laparoscope to dissect the left hepatic artery, hang over the hepatoduodenal ligament except the left hepatic artery to block liver blood flow and then resect the liver cancer by transdiaphragmatic thoracoscopy.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 291-294 . [Abstract] ( 94 ) [HTML 1KB] [PDF 0KB] ( 150 )

	295	Cao LP, Zhang C, Weng XY, Xie HY, Wu J, Zheng SS
		Synergistic interaction between thioredoxin inhibitor 1-methylpropyl 2-imidazolyl disulfide and sorafenib in liver cancer cells
		Hepatocellular carcinoma (HCC) is a major health problem worldwide with high incidence and mortality rate [1,2] . Proper treatments for HCC mainly include surgical resection, transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), and liver transplantation. However, many patients who are diagnosed with advanced HCC are not eligible for surgery, even the TACE and RFA does not necessarily have a good therapeutic effect. Until now, sorafenib is currently the first-line antitumor drug for the treatment of patients with advanced HCC.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 295-298 . [Abstract] ( 93 ) [HTML 1KB] [PDF 0KB] ( 156 )

LETTERS TO THE EDITOR

	299	Li L, Dong Y, Li RD, Tao YF, Shen CH, Wang ZX
		Sinusoidal obstruction syndrome related to tacrolimus following liver transplantation
		Sinusoidal obstruction syndrome (SOS), also known as venoocclusive disease, is characterized by fibrotic occlusion of small hepatic veins and congestion of sinusoids [1] . This syndrome is mainly observed in hematopoietic stem cell transplantation (HSCT) and its incidence in liver transplantation (LT) ranges from 1.9% to 2.9% [2,3] . Although rare, severe SOS following LT can cause liver graft dysfunction with poor prognosis [3] .
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 299-302 . [Abstract] ( 98 ) [HTML 1KB] [PDF 0KB] ( 130 )

	303	Cocomazzi F, Castellaneta NM, Castellaneta A, Fucilli F, Ierardi E, Di Leo A
		Transjugular intrahepatic portosystemic shunt for a patient with chylothorax in cryptogenic/metabolic cirrhosis
		Chylothorax is a rare pleural effusion with a milky appearance due to triglycerides and chylomicrons [1] ; About 1% of cases are associated with liver cirrhosis [2] . Incidentally, it has been hypothesized that chylothorax originates from the passage of chylous ascites into pleural cavity owing to diaphragmatic defects and negative thoracic pressure [3] . Chylous ascites represents the 1% of ascites in liver cirrhosis (1:20,0 0 0 hospitalizations) [4] . Pathophysiological mechanism is mediated by increased hepatic and gastrointestinal lymphatic flow due to portal hypertension [5] , which may lead to lymphatic vessel spontaneous rupture [6–8] . The gold standard for diagnosis of chylothorax is the presence of chylomicrons in the fluid [9 , 10] . If this analysis is not available, triglycerides concentration > 110 mg/dL is the diagnostic cut-off value. In addition, other diagnostic criteria include pleural/serum triglycerides ratio > 1 and pleural/serum cholesterol ratio < 1 [9] . In the case of liver cirrhosis, according to Light’s criteria, chylothorax is usually a transudate fluid [11] , which is defined by the absence of the following parameters: (a) pleural fluid/serum protein level > 0.5; (b) pleural fluid lactic/serum lactic acid dehydrogenase (LDH) level > 0.6; (c) pleural fluid LDH level > 2/3 upper serum normal limit [12] . Therapeutic approach can be both conservative and interventional. The objective of conservative treatment is lymphatic vessel spontaneous closure [10] . In cirrhotic patients, portal decompression may be a successful option [5,13] . A review of Tsauo et al. [5] reported that 7 patients with chylothorax and liver cirrhosis were treated with transjugular intrahepatic portosystemic shunt (TIPS). Despite the putative effectiveness, the small sample does not allow providing final recommendations about its use in first-line.
		Hepatobiliary Pancreat Dis Int. 2020; 19(3): 303-304 . [Abstract] ( 91 ) [HTML 1KB] [PDF 0KB] ( 188 )

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