Hepatobiliary Pancreat Dis Int

	2023 Vol. 22 No. 4
	Published: 2023-08-15


	Pages 331-440
	EDITORIAL REVIEW ARTICLES ORIGINAL ARTICLES/Transplantation ORIGINAL ARTICLES/Liver ORIGINAL ARTICLES/Biliary ORIGINAL ARTICLES/Pancreas CLINICAL IMAGE LETTERS TO THE EDITOR

EDITORIAL

	331	He Z, Yang HY
		Mechanism of hepatocytes differentiation and dedifferentiation in liver regeneration: Process and exploration
		The liver has roles in many processes, including metabolism, synthesis, and biotransformation. It is unique among all visceral organs, as it even can regenerate after injury. A common research model of liver regeneration is the 2/3 partial hepatectomy (PHx) model in animals, like rodents, in which the left lateral, left medial, and right medial hepatic lobes are surgically removed [1]. Moreover, with the ability of hepatocyte hypertrophy and hyperplasia, within 7-10 days, the rest liver regenerates to its original size [2]. Jo and colleagues [3] reported that splanchnic vasoactive agents could decrease portal vein pressure to facilitate the liver regeneration after 70% hepatectomy. However, liver regeneration and function maintenance need adequate mass of future remnant liver. Inadequate mass of future remnant liver results in liver failure which loses the opportunity for the liver to regenerate and therefore, it is important to keep an adequate future remnant liver to avoid posthepatectomy liver failure [4].
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 331-332 . [Abstract] ( 59 ) [HTML 1KB] [PDF 0KB] ( 152 )

REVIEW ARTICLES

	333	Shree Harini K, Ezhilarasan D
		Wnt/beta-catenin signaling and its modulators in nonalcoholic fatty liver diseases ^Hot!
		Nonalcoholic fatty liver disease (NAFLD) is a global health concern associated with significant morbidity and mortality. NAFLD is a spectrum of diseases originating from simple steatosis, progressing through nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis that may lead to hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is mediated by the triglyceride accumulation followed by proinflammatory cytokines expression leading to inflammation, oxidative stress, and mitochondrial dysfunction denoted as “two-hit hypothesis”, advancing with a “third hit”of insufficient hepatocyte proliferation, leading to the increase in hepatic progenitor cells contributing to fibrosis and HCC. Wnt/β-catenin signaling is responsible for normal liver development, regeneration, hepatic metabolic zonation, ammonia and drug detoxification, hepatobiliary development, etc., maintaining the overall liver homeostasis. The key regulators of canonical Wnt signaling such as LRP6, Wnt1, Wnt3a, β-catenin, GSK-3 β, and APC are abnormally regulated in NAFLD. Many experimental studies have shown the aberrated Wnt/β-catenin signaling during the NAFLD progression and NASH to hepatic fibrosis and HCC. Therefore, in this review, we have emphasized the role of Wnt/β-catenin signaling and its modulators that can potentially aid in the inhibition of NAFLD.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 333-345 . [Abstract] ( 76 ) [HTML 1KB] [PDF 0KB] ( 139 )

	346	Jiang C, Cai YQ, Yang JJ, Ma CY, Chen JX, Huang L, Xiang Z, Wu J
		Radiomics in the diagnosis and treatment of hepatocellular carcinoma ^Hot!
		Hepatocellular carcinoma (HCC) is a common malignant tumor. At present, early diagnosis of HCC is difficult and therapeutic methods are limited. Radiomics can achieve accurate quantitative evaluation of the lesions without invasion, and has important value in the diagnosis and treatment of HCC. Radiomics features can predict the development of cancer in patients, serve as the basis for risk stratification of HCC patients, and help clinicians distinguish similar diseases, thus improving the diagnostic accuracy. Furthermore, the prediction of the treatment outcomes helps determine the treatment plan. Radiomics is also helpful in predicting the HCC recurrence, disease-free survival and overall survival. This review summa- rized the role of radiomics in the diagnosis, treatment and prognosis of HCC.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 346-351 . [Abstract] ( 75 ) [HTML 1KB] [PDF 0KB] ( 136 )

ORIGINAL ARTICLES/Transplantation

	352	Ding LM, Deng LS, Qian JJ, Liu G, Zhou L, Zheng SS
		Clinical analysis of Wernicke encephalopathy after liver transplantation
		Background: Wernicke encephalopathy (WE) is an acute neurological disease resulting from vitamin B1 deficiency, and there are only very few case reports of WE after liver transplantation. The present study aimed to investigate the clinical characteristics, etiology, magnetic resonance imaging (MRI) features, treatment and prognosis of patients with WE after liver transplantation. Methods: Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital, Zhejiang University School of Medicine and Jiangxi Provincial People’s Hospital between January 2011 and December 2021 were retrospectively analyzed. Results: Among the 23 patients diagnosed with WE after liver transplantation, 6 (26%) had a classic triad of impaired consciousness, oculomotor palsy and ataxia, and 17 (74%) had two features. The misdiagno- sis rate was 65%. After treatment with high-dose vitamin B1, 19 (83%) patients showed improvement, whereas 4 (17%) showed no improvement, including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia. Conclusions: The misdiagnosis rate is high in the early stage of WE, and the prognosis is closely associated with whether WE is diagnosed early and treated timely. High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment. Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 352-357 . [Abstract] ( 56 ) [HTML 1KB] [PDF 0KB] ( 49 )

ORIGINAL ARTICLES/Liver

	358	Guo ZY, Hong Y, Tu B, Cheng Y, Wang XM
		Laparoscopic liver resection for hepatocellular carcinoma complicated with significant portal hypertension: A propensity score-matched survival analysis ^Hot!
		Background: Significant portal hypertension (SPH) is a relative contraindication for patients with resectable hepatocellular carcinoma (HCC). However, increasing evidence indicates that liver resection is feasible for HCC patients with SPH. Methods: HCC patients with cirrhosis who underwent laparoscopic liver resection (LLR) in two centers from January 2013 to April 2018 were included. Surgical and survival outcomes were analyzed to explore potential prognostic factors. Propensity score matching (PSM) analysis was performed to minimize bias. Results: A total of 165 patients were divided into two groups based on the presence (SPH, n = 76) or absence (non-SPH, n = 89) of SPH. Patients in the SPH group had longer operative time, more blood loss, and more advanced TNM stage than patients in the non-SPH group ( P < 0.05). However, there were no significant differences in the postoperative 90-day mortality rate ( n = 0), overall postoperative complications (47.4% vs. 41.6%, P = 0.455), Clavien-Dindo classification ( P = 0.347), conversion to open surgery (9.2% vs. 6.7%, P = 0.557), or length of hospitalization (16 vs. 15 days, P = 0.203) between the SPH and non-SPH groups before PSM. Similar results were obtained after PSM. The 1-, 3-, and 5-year overall sur- vival (OS) and recurrence-free survival rates in the SPH group were not significantly different from those in the non-SPH group both before and after PSM (log-rank P > 0.05). After PSM, alpha-fetoprotein (AFP) ≥400 μg/L [hazardratio (HR)=4.71, 95%confidence interval(CI): 2.69-8.25], ascites (HR=2.18, 95% CI: 1.30-3.66), American Society of Anesthesiologists (ASA) classification (III vs. II) (HR = 2.13, 95% CI: 1.11-4.07) and tumor diameter > 5 cm (HR = 3.91, 95% CI: 2.02-7.56) independently predicted worse OS. Conclusions: LLR for patients with HCC complicated with SPH appears feasible at the price of increas- ing operative time and blood loss. AFP, ascites, ASA classification and tumor diameter may predict the prognosis of HCC complicated with SPH after LLR.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 358-365 . [Abstract] ( 92 ) [HTML 1KB] [PDF 0KB] ( 51 )

	366	Xiong KG, Ke KY, Chen LF, Kong JF, Lin TS, Lin QB, Lin S, Zhu YY
		The impact of metabolic dysfunction–associated fatty liver disease on the prognosis of patients with hepatocellular carcinoma after radical resection
		Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently proposed an entity by a group of international experts. However, the impact of MAFLD on the prognosis of patients with hepatocellular carcinoma (HCC) is not clear. The aim of this study was to explore the influence of MAFLD for the prognosis of HCC after radical resection. Methods: HCC patients who received radical resection were enrolled. The recurrence-free survival (RFS) and overall survival (OS) were compared between MAFLD and non-MAFLD. Results: A total of 576 HCC patients were included, and among them 114 (19.8%) met the diagnostic criteria of MAFLD. The median RFS was 34.0 months in the MAFLD group and 19.0 months in the non-MAFLD group. The 1-, 3-, and 5-year RFS rates were 64.9%, 49.1% and 36.1% in the MAFLD group, which were higher than those of the non-MAFLD group (59.4%, 35.3% and 26.5%, respectively, P = 0.01). The mean OS was 57.0 months in the MAFLD group and 52.2 months in the non-MAFLD group. There was no statistical difference in OS rate between the MAFLD group and non-MAFLD group. Similar results were found in HBV-related HCC patients in the subgroup analysis. Univariate analysis revealed that MAFLD was a protective factor for RFS in HCC patients after radical resection (P < 0.05), and there was no association between MAFLD and OS rate (P > 0.05). Multivariate analysis demonstrated that MAFLD was not an independent protective factor for HCC patients with radical resection. Conclusions: MAFLD improves RFS rate in HCC patients with radical resection, but is not an independent protective factor and not associated with OS rate.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 366-372 . [Abstract] ( 51 ) [HTML 1KB] [PDF 0KB] ( 71 )

	373	Wang H, Yin YP, Wang ZL, Qian Y, Fan YC, Liu HH, Wang K
		Hypermethylation of thymosin β4 predicts a poor prognosis for patients with acute-on-chronic hepatitis B liver failure
		Background: It has been demonstrated that thymosin β4 (T β4) could inflect the severity of acute-on-chronic hepatitis B liver failure (ACHBLF), but the relationship between its methylation status and the prognosis of liver failure is not clear. This study aimed to determine T β4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value. Methods: The study recruited 115 patients with ACHBLF, 80 with acute-on-chronic hepatitis B pre-liver failure (pre-ACHBLF), and 86 with chronic hepatitis B (CHB). In addition, there were 36 healthy controls (HCs) from the Department of Hepatology, Qilu Hospital of Shandong University. The 115 patients with ACHBLF were divided into three subgroups: 33 with early stage ACHBLF (E-ACHBLF), 42 with mid-stage ACHBLF (M-ACHBLF), and 40 with advanced stage ACHBLF (A-ACHBLF). T β4 promoter methylation status in peripheral blood mononuclear cells (PBMCs) was measured by methylation-specific polymerase chain reaction, and mRNA was detected by quantitative real-time polymerase chain reaction. Results: Methylation frequency of T β4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF, CHB or HCs. However, expression of T β4 mRNA showed the opposite trend. In patients with ACHBLF, T β4 promoter methylation status correlated negatively with mRNA levels. The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group. Also, T β4 promoter methylation frequency was lower in survivors than in non-survivors. When used to predict the 1-, 2-, and 3-month incidence of ACHBLF, T β4 methylation status was better than the model for end-stage liver disease (MELD) score. The predictive value of T β4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF, but not for A-ACHBLF. Conclusions: T β4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 373-382 . [Abstract] ( 56 ) [HTML 1KB] [PDF 0KB] ( 59 )

	383	Wu D, Yin YQ, Li Y, Zhang L, Jiang YH, Wang Z
		CK2α causes stemness and chemotherapy resistance in liver cancer through the Hedgehog signaling pathway
		Background: Liver cancer is one of the major causes of cancer-related deaths globally. Cancer cell stemness and chemotherapy resistance contribute to the high mortality. Although evidence indicates that the alpha subunit of protein kinase 2 (CK2α) is involved in several human cancers, its function in liver cancer remains unknown. In the present study, we aimed to elucidate the role of CK2α in liver cancer. Methods: We examined the role of CK2α regulation in stemness and chemotherapy resistance capacity of liver cancer cells. MTT assays, tumor sphere formation assays, RT-PCR, flow cytometry, Western blotting assay, clonogenicity assay, matrigel invasion assay and bioinformatics were conducted in this study. Results: CK2α expression in the liver cancer tissues was notably upregulated compared with that in the corresponding non-tumorous tissues. The overexpression of CK2α promoted tumor sphere formation, increased the percentage of CD133(+) and side population cells, caused the resistance of liver cancer cells to 5-FU treatment, increased the expression levels of NANOG, OCT4, SOX2, Gli1 and Ptch1, and enhanced the ability of CD133(+) cell clone formation and invasion. Consistently, the downregulation of CK2α had the opposite effects. CK2α silencing inhibited the Hedgehog pathway by reducing the expression of Gli1 and Ptch1. Mechanistically, CK2α regulation on liver cancer cell stemness and chemotherapy resistance was found to be involved in the Hedgehog signaling pathway. Conclusions: Our study may bring some new insights into the occurrence of liver cancer. Furthermore, these findings suggest that targeting CK2α may be a novel therapeutic strategy for patients with liver cancer.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 383-391 . [Abstract] ( 47 ) [HTML 1KB] [PDF 0KB] ( 62 )

ORIGINAL ARTICLES/Biliary

	392	Li T, Hao LX, Lv C, Li XJ, Ji XD, Chen M, Liu C, Bie LK, Gong B
		Long-term outcomes of endoscopic papillary large-balloon dilation (12-15 mm) with or without limited sphincterotomy for removal of bile duct stones
		Background: Limited endoscopic sphincterotomy with large balloon dilation (ES-LBD) and endoscopic papillary large-balloon dilation (EPLBD) have been proven safe and effective for removal of bile duct stones. However, the long-term outcomes are not clear. The aim of this study was to assess the long-term outcomes of EPLBD (12-15 mm) with or without limited sphincterotomy for removal of common bile duct (CBD) stones. Methods: Patients with EPLBD or ES-LBD referred for the removal of bile-duct stones between June 2008 and August 2020 were retrospectively reviewed. Complete stone clearance, endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events, and late biliary complications during long-term follow-up were analyzed. Results: Basic patient characteristics were not significantly different between the groups that underwent EPLBD ( n = 168) and ES-LBD ( n = 57). EPLBD compared with ES-LBD resulted in similar outcomes in terms of overall successful stone removal (99.4% vs. 100%, P = 1.00) and ERCP-related adverse events (7.7% vs. 5.3%, P = 0.77). The mean duration of the follow-up were 113.6 months and 106.7 months for patients with EPLBD and ES-LBD, respectively ( P = 0.13). There was no significant difference between EPLBD and ES-LBD in the incidence of stone recurrence [20 (11.9%) vs. 9 (15.8%); P = 0.49]. Multivariate analysis showed that a diameter of CBD ≥15 mm (OR = 3.001; 95% CI: 1.357–6.640; P = 0.007) was an independent risk factor for stone recurrence. Conclusions: The application of a large balloon (12–15 mm) via EPLBD is an effective and safe alternative to ES-LBD for extraction of large CBD stones. Endoscopic sphincterotomy prior to EPLBD may be unnecessary. A diameter of CBD ≥15 mm is a risk factor of stone recurrence.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 392-398 . [Abstract] ( 54 ) [HTML 1KB] [PDF 0KB] ( 59 )

ORIGINAL ARTICLES/Pancreas

	399	Kang D, Park SH, Oh C, Kim YJ, Kim JB, Park SH, Lee MS, Park JK
		Prevalence and prognosis of acute pancreatitis in critically ill patients with COVID-19
		Background: Coronavirus disease 2019 (COVID-19) is a global pandemic issue. In addition to the well-known respiratory and fever symptoms, gastrointestinal symptoms have also been reported. This study aimed to evaluate the prevalence and prognosis of patients with COVID-19 infection complicated with acute pancreatitis in intensive care unit (ICU). Methods: This was a retrospective observational cohort study, and patients aged 18 years or older, admitted into the ICU in a single tertiary center from January 1, 2020, to April 30, 2022 were enrolled. Patients were identified by electronic medical records and reviewed manually. The primary outcome was the prevalence of acute pancreatitis among ICU patients with COVID-19. The secondary outcomes were the length of hospital stay, need for mechanical ventilation (MV), need for continuous renal replacement therapy (CRRT), and in-hospital mortality. Results: A total of 4133 patients, admitted into the ICU, were screened. Among these patients, 389 were infected by COVID-19, and 86 were diagnosed with acute pancreatitis. COVID-19 positive patients were more likely to present with acute pancreatitis than COVID-19 negative patients (odds ratio = 5.42, 95% confidence interval: 2.35-6.58, P < 0.01). However, the length of hospital stay, need for MV, need for CRRT, and in-hospital mortality were not significantly different between acute pancreatitis patients with and without COVID-19 infection. Conclusions: Severe COVID-19 infections may cause acute pancreas damage in critically ill patients. However, the prognosis may not differ between acute pancreatitis patients with and without COVID-19 infection.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 399-402 . [Abstract] ( 50 ) [HTML 1KB] [PDF 0KB] ( 54 )

CLINICAL IMAGE

	403	Wang XD, Ge NJ, He CJ, Zhu JJ, Xu W, Yang YF
		Endovascular treatment of delayed arterial hemorrhage after radical operation for hilar cholangiocarcinoma
		Radical operation for hilar cholangiocarcinoma (HCCA) is the most effective treatment, but high rates of severe postoperative complication and death remain concerns due to the complexity of biliary and vascular anatomy of the hepatobiliary region. Delayed arterial hemorrhage (DAH) occurring > 24 h postoperatively usually causes life-threatening bleeding, and relaparotomy for DAH would be difficult and hazardous because of postoperative adhesions and critical general condition. As endovascular technique is less invasive and has improved over the recent decades, clinicians have begun to prefer endovascular treatment (EVT) to surgical treatment of DAH after hepatobiliary pancreatic surgery. However, to our knowledge, a relatively large series of patients dealing with the outcomes of EVT of DAH after surgery for HCCA has not been reported. Herein, we analyzed the technical and clinical outcomes of EVT in 17 patients to evaluate the efficacy and safety of EVT.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 403-405 . [Abstract] ( 63 ) [HTML 1KB] [PDF 0KB] ( 45 )

	406	Mownah OA, Leahy JD, Summers J, Gregory SM, Heaton ND
		Regression of recurrent granulosa cell tumor liver metastases following selective internal radiation therapy
		Granulosa cell tumor (GCT) is the most common sex cordstromal tumor, comprising 5% of all ovarian malignancies [1]. The disease course is indolent, and the majority of cases present at stage 1. However, metastases may develop with potential sites being peritoneum, lung, brain, liver and bone [2]. Due to the rarity of the disease, published evidence for management of granulosa cell tumor liver metastases (GCTLM) is limited. Surgical resection is the optimal treatment in instances where there is a high chance of achieving complete resection [3]. With regards to unresectable GCTLM there is a paucity of evidence to guide treatment strategy.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 406-408 . [Abstract] ( 55 ) [HTML 1KB] [PDF 0KB] ( 50 )

	409	Tang R, Wu GD, Li A, Yu LH, Tong X, Yan J, Lu Q
		Caudate lobe-sparing subtotal hepatectomy as treatment for extensive intrahepatic arterioportal fistula
		Intrahepatic arterioportal fistulas (APFs) are abnormal hepatic artery and portal vein (PV) communications that develop as a result of congenital malformation, trauma, ruptured hepatic aneurysm, cirrhosis, tumor-related changes, biopsy, chemotherapy or iatrogenic causes [1,2]. The most common symptoms are gastrointestinal bleeding and ascites secondary to portal hypertension; other symptoms include abdominal pain, pyrexia, edema, back pain and jaundice [3]. The main goal of therapy is to decrease the portal pressure with variceal bleeding being the absolute indication for surgical management. Transarterial embolization (TAE) should be the first choice to treat APFs, while resection, portocaval shunt and even transplantation may cure APFs in the case of TAE failure [4]. In previous reports, caudate lobe-sparing subtotal hepatectomy (CLSSH) has been applied for the treatment of primary hepatolithiasis and hepatocellular carcinoma [5,6]. As far as we know, this is the first report describing CLSSH as treatment for an extensive intrahepatic APF, which involved segments 2 to 8, with corresponding hypertrophy of the caudate lobe.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 409-411 . [Abstract] ( 52 ) [HTML 1KB] [PDF 0KB] ( 57 )

	412	Ciardiello D, Urbano F, Zamboni G, Palladino N, Bazzocchi F, Parente P
		Left abdominal mass with carcinosis: Unusual presentation of pancreatic acinar cell carcinoma
		Acinar cell carcinoma (ACC) is a rare malignant epithelial neoplasm accounting for 1%-2% of all pancreatic exocrine neoplasm, affecting more frequently man with an age between 50 and 70 years. Most patients present with nonspecific symptoms, which may give rise to difficulties in clinical diagnosis [1]. ACC can manifest with diarrhea, weight loss, abdominal pain and, in up to 10%-15%, with lipase hypersecretion syndrome, characterized by elevated lipase production, diffuse subcutaneous fat necrosis and polyarthralgia [1,2]. Biliary obstruction and jaundice are infrequent clinical manifestations, unlike ductal adenocarcinoma, due to pushing rather than infiltrating growth of ACC. This neoplasm may arise in any portion of the pancreas, with a decreasing frequency in the head, the tail, both the body and the tail/head, respectively [2]. Among the 31 cases reported, only three cases involving the whole pancreas were described [3,4]. Imaging is essential for detection and preoperative diagnosis in ACC management. Imaging features of ACC in computed tomography (CT) and magnetic resonance (MR) reveal an exophytic well-marginated mass originating from the pancreas, round to oval in shape, with a varied degree of cystic components that enhance homogeneously less than the surrounding normal pancreas [5]. Here, we describe an unusual case of left abdominal mass, infiltrating the intestinal wall, without radiologically documented connection with the pancreas, with synchronous peritoneal carcinoma, histologically corresponding to ACC.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 412-414 . [Abstract] ( 51 ) [HTML 1KB] [PDF 0KB] ( 48 )

LETTERS TO THE EDITOR

	415	Cosentino C, Clayton-Chubb D, McLean C, Roberts SK, Kemp W
		Isolated IgG4-associated autoimmune hepatitis or the first manifestation of IgG4-related disease?
		Immunoglobulin G4 (IgG4)-associated autoimmune hepatitis (IgG4-AIH) is a novel and rare disease entity, characterized by significant infiltration of IgG4-expressing plasma cells in the liver. The classification of of IgG4-AIH as a subtype of AIH or an early manifestation of IgG4-related disease (IgG4-RD) remains controversial. Herein, we discuss an interesting clinical vignette of IgG4-AIH in a gentleman with no significant past medical history, who presented with undifferentiated symptoms and elevated aminotransferases.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 415-417 . [Abstract] ( 53 ) [HTML 1KB] [PDF 0KB] ( 3347 )

	418	Li T, Zhu LJ, Huang AM, Wei YF, Xu J, Xu YJ
		*The role of targeting protein for Xklp2* in tumorigenesis of hepatocellular carcinoma**
		Hepatocellular carcinoma (HCC) is a prevalent form of gastrointestinal malignancies. The current combination of immunotherapy and other treatments improves overall survival compared to conventional therapies, but the immunosuppressive microenvironment of HCC is a significant barrier to the efficacy of immunotherapeutic drugs [1]. Tumor immune escape is promoted by interactions among immunosuppressive cells, including tumor-associated macrophages, marrow-derived suppressor cells, tumor-associated neutrophils, cancer-associated fibroblasts, and tumor-infiltrating Tregs [2].
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 418-422 . [Abstract] ( 62 ) [HTML 1KB] [PDF 0KB] ( 50 )

	423	Feng YY, Xu MZ
		Risk factors for posttransplant diabetes in patients with hepatocellular carcinoma
		Hepatocellular carcinoma (HCC) is one of the most common cause of cancer death worldwide, and in China, primary HCC ranks 4th for incidence and 2nd for mortality among all cancers [1]. Traditionally, the gold standard treatment for HCC is surgical resection, but most patients are not fit due to the advanced disease. In the 1980s, liver transplantation emerged as the treatment of choice for end-stage liver disease and also became an option for HCC patients [2]. But elevated blood glucose is a common complication after liver transplantation, affecting approximately 20%-40% of liver recipients [3]. Posttransplant diabetes mellitus (PTDM) refers to newly diagnosed diabetes mellitus (DM) after transplantation, regardless of timing or presence but undetected before transplantation [4]. In addition to all well-known complications of DM, PTDM is associated with reduced graft function, increased risk of graft failure, acute kidney injury, and increased cardiovascular risk and mortality in liver recipients [5,6]. Therefore, identifying highrisk patients and taking steps to limit the development of PTDM may improve the long-term prognosis of patients [7] . This study aimed to explore the risk factors influencing the development of PTDM after liver transplantation in HCC patients, to provide interventions for different populations before and after surgical treatment, to prevent postoperative blood glucose elevation and to improve clinical outcomes.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 423-425 . [Abstract] ( 50 ) [HTML 1KB] [PDF 0KB] ( 49 )

	426	Szempruch KR, Lachiewicz AM, Williams BM, Kumar A, Baldwin X, Desai CS
		Microbiological cultures and antimicrobial prophylaxis in patients undergoing total pancreatectomy with islet cell autotransplantation
		Total pancreatectomy with islet cell autotransplantation (TPIAT) is a viable treatment option upon failed endoscopic and medical therapy for patients with chronic pancreatitis. This procedure involves surgical removal of the entire pancreas, isolation of islet cells and re-infusion of these cells into the liver via portal vein [1,2]. The risk of contamination to the final islet cell product can occur at several stages of the isolation procedure [3]. In order to ensure the sterility of the islet cell product, multiple samples from the preservation and cannulation solution, and the final islet cell product are sent for bacterial cultures. Prior studies have found variable clinical consequences of these cultures on infectious complications or graft function [3–9]. Herein we aimed to determine the incidence of infection in 60 days post-TPIAT and its association with the culture data.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 426-429 . [Abstract] ( 50 ) [HTML 1KB] [PDF 0KB] ( 60 )

	430	Porcu A, Deiana G, Feo CF, Ninniri C, Turilli D, Tanda L, Fancellu A
		Hepatopancreatoduodenectomy for the treatment of extrahepatic cholangiocarcinoma ?
		Extrahepatic cholangiocarcinoma (ECC) is an uncommon neoplasm associated with a poor prognosis [1–3]. Surgical resection represents the only curative approach, since systemic treatments have scarce efficacy in achieving disease control. However, only 10%-40% of patients with ECC are resectable at diagnosis [1] . Major hepatectomy and portal lymphadenectomy are usually required for hilar ECC, while pancreatoduodenectomy is the standard operation for distal ECC [3–5]. However, ECC may spread horizontally along the biliary tree, causing tumor involvement of the entire extrahepatic biliary system. In these circumstances, hepatopancreatoduodenectomy (HPD) has been proposed as a procedure with curative intent [2,6,7]. HPD is a complex operation which includes the combination of hepatic resection, pancreatoduodenectomy and extirpation of the extrahepatic biliary system. It has been generally considered a controversial operation, due to the high mortality and morbidity rates in front of uncertain oncological outcomes [5,7-9]. However, in the last 5 years, encouraging survival outcomes, as well as acceptable mortality and morbidity rates, have been reported from surgical teams with high expertise in hepatobiliopancreatic (HBP) surgery [ 2,10,11]. Most literature data focusing on HPD are from Asian institutions, where HPD has been gaining some popularity in the treatment of selected patients with ECC and gallbladder cancer. On the opposite, few reports came from Western countries, where HPD has not been considered a worthwhile, albeit feasible, procedure.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 430-433 . [Abstract] ( 42 ) [HTML 1KB] [PDF 0KB] ( 51 )

	434	Ogura T, Uba Y, Tomita M, Bessho K, Nishikawa H
		Novel re-intervention device for occluded multiple uncovered self-expandable metal stent (with video)
		Obstructive jaundice due to unresectable malignant hilar obstruction can be treated by deployment of bilateral uncovered selfexpandable metal stents (UCSEMSs), which enable longer stent patency to be obtained compared with multiple plastic stents [1–3]. However, re-intervention is needed if obstructive jaundice occurs after bilateral UCSEMS deployment. During re-intervention procedures, insertion of the stent delivery system across the mesh of a UCSEMS and into the bile duct can be challenging. A novel drill dilator has recently become available in Japan (Tornus ES; Asahi Intecc, Nagoya, Japan) ( Fig. 1) [4]. The tract is easily dilated using a clockwise rotation. We herein describe a successful reintervention using this device for a patient with occluded bilateral UCSEMSs.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 434-436 . [Abstract] ( 55 ) [HTML 1KB] [PDF 0KB] ( 45 )

	437	Polyzos SA, Kountouras J, Anastasilakis AD, Terpos E
		Wnt/beta-catenin signaling inhibitors and nonalcoholic fatty liver disease: Potential therapeutic implications
		We read with considerable interest the paper of Shree Harini and Ezhilarasan, summarizing the possible pathophysiological connections between the modulators of canonical Wnt/ β-catenin pathway and nonalcoholic fatty liver disease (NAFLD) [1]. The authors supported with evidence that Wnt/ β-catenin signaling contributes to hepatic homeostasis by regulating hepatic development, regeneration and metabolism. They also supported that dysregulation of modulators of Wnt/ β-catenin signaling is not only implicated in the development of NAFLD, but also in its progression to nonalcoholic steatohepatitis (NASH), hepatic fibrosis and hepatocellular carcinoma (HCC).
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 437-438 . [Abstract] ( 58 ) [HTML 1KB] [PDF 0KB] ( 55 )

	439	Shree Harini K, Ezhilarasan D
		Reply to “Wnt/beta-catenin signaling inhibitors and nonalcoholic fatty liver disease: Potential therapeutic implications”
		We sincerely appreciated the interest of Polyzos et al., in our review article and sharing their improvised thoughts regarding the Wnt signaling modulators for the treatment of postmenopausal women with osteoporosis and nonalcoholic fatty liver disease (NAFLD). Several experimental studies have showed that the aberrant Wnt/ β-catenin signaling promotes the development and/or progression of a variety of chronic liver diseases including NAFLD [1,2]. Therefore, our review emphasized on the modulation of Wnt/ β-catenin signaling and the role of its mediators in NAFLD progression. Given that NAFLD prevalence is constantly increasing, and that osteoporosis is associated with women over 50 years of age with NAFLD [3] , there is an unmet need for an effective treatment. Sclerostin blocks the canonical Wnt signaling pathway of bone formation. Therefore, romosozumab, a humanized antisclerostin monoclonal antibody, was approved for the treatment of osteoporosis. Romosozumab binds to sclerostin, permitting the engagement of Wnt ligands with their co-receptors, resulting in an increase in bone formation and bone mineral density.
		Hepatobiliary Pancreat Dis Int. 2023; 22(4): 439-440 . [Abstract] ( 77 ) [HTML 1KB] [PDF 0KB] ( 58 )

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