Hepatobiliary Pancreat Dis Int

	2019 Vol. 18 No. 5
	Published: 2019-10-15


	Pages 403-502
	REVIEW ARTICLES ORIGINAL ARTICLES/Transplantation ORIGINAL ARTICLES/Liver ORIGINAL ARTICLES/Biliary ORIGINAL ARTICLES/Pancreas CLINICAL IMAGE LETTERS TO THE EDITOR VIEWPOINTS

REVIEW ARTICLES

	403	Chen P,Wang YY, Chen C, Guan J, Zhu HH, Chen Z
		The immunological roles in acute-on-chronic liver failure: An update ^Hot!
		Background: Acute-on-chronic liver failure (ACLF) refers to the acute deterioration of liver function that occurs in patients with chronic liver disease. ACLF is characterized by acute decompensation, organ failure and high short-term mortality. Numerous studies have been conducted and remarkable progress has been made regarding the pathophysiology and pathogenesis of this disease in the last decade. The present review was to summarize the advances in this field. Data sources: A comprehensive search in PubMed and EMBASE was conducted using the medical subject words “acute-on-chronic liver failure”, ACLF”, “pathogenesis”,“predictors”, and “immunotherapy”combined with free text terms such as “systemic inflammation”and “immune paralysis”. Relevant papers published before October 31, 2018, were included. Results: ACLF has two marked pathophysiological features, namely, excessive systemic inflammation and susceptibility to infection. The systemic inflammation is mainly manifested by a significant increase in the levels of plasma pro-inflammatory factors, leukocyte count and C-reactive protein. The underlying mechanisms are unclear and may be associated with decreased immune inhibitory cells, abnormal expression of cell surface molecules and intracellular regulatory pathways in immune cells and increased damage-associated molecular patterns in circulation. However, the main cause of susceptibility to infection is immune paralysis. Immunological paralysis is characterized by an attenuated activity of immune cells. The mechanisms are related to elevations of immune inhibitory cells and the concentration of plasma anti-inflammatory molecules. Some immune biological indicators, such as soluble CD163, are used to explore the pathogenesis and prognosis of the disease, and some immunotherapies, such as glucocorticoids and granulocyte colony-stimulating factor, are effective on ACLF. Conclusions: Overwhelming systemic inflammation and susceptibility to infection are two key features of ACLF. A better understanding of the state of a patient’s immune system will help to guide immunotherapy for ACLF.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 403-411 . [Abstract] ( 67 ) [HTML 1KB] [PDF 0KB] ( 100 )

ORIGINAL ARTICLES/Transplantation

	412	Lerut J, Iesari S, Vandeplas G, Fabbrizio T, Ackenine K, Inostroza Nunez ME, Komuta M, Coubeau L, Ciccarelli O, Bonaccorsi-Riani E
		Secondary non-resectable liver tumors: A single-center living-donor and deceased-donor liver transplantation case series ^Hot!
		Background: During the last decades, deceased-donor liver transplantation (DDLT) has gained a place in the therapeutic algorithm of well-selected patients harbouring non-resectable secondary liver tumors. Living-donor LT (LDLT) might represent a valuable means to further expand this indication for LT. Methods: Between 1985 and 2016, twenty-two adults were transplanted because of neuroendocrine (n = 18, 82%) and colorectal metastases (n = 4, 18%); 50% received DDLT and 50% LDLT. In LDLT, 4 (36%) right and 7 (64%) left grafts were used; the median graft-to-recipient-weight ratios (GRWR) were 1.03% (IQR 0.86% - 1.30%) and 0.59% (IQR 0.51% - 0.91%), respectively. Median post-LT follow-up was 64 months (IQR 17–107) in the DDLT group and 40 months (IQR 35–116) in the LDLT group. DDLT and LDLT recipients were compared in terms of overall survival, graft survival, postoperative complications and recurrence. Results: The 1- and 5-year actuarial patient survivals were 82% and 55% after DDLT, 100% and 100% after LDLT, respectively ( P < 0.01). One- and 5-year actuarial graft survivals were 73% and 36% after DDLT, 91% and 91% after LDLT ( P < 0.01). The outcomes of right or left LDLT were comparable. Donor hepatectomy proved safe, and one donor experienced a Clavien IIIb complication. Bilirubin peak was significantly lower after left hepatectomy compared with that after right hepatectomy [1.3 (IQR 1.2–2.2) vs. 3.3 (IQR 2.3–5.2) mg/dL; P = 0.02]. Conclusions: The more recent LDLT series compared favorably to our DDLT series in the treatment of secondary liver malignancies. The absence of portal hypertension and the use of smaller left grafts make recipient and donor surgeries safe. The safety of the procedures and lack of interference with the scarce allograft pool are expected to lead to a more frequent use of LDLT in the field of transplant oncology.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 412-422 . [Abstract] ( 59 ) [HTML 1KB] [PDF 0KB] ( 99 )

	423	Bastos-Neves D, Salvalaggio PR, Almeida MD
		Risk factors, surgical complications and graft survival in liver transplant recipients with early allograft dysfunction ^Hot!
		Background: Early allograft dysfunction (EAD) is a severe complication after liver transplantation. The associated risk factors and complications have regained recent interest. This study investigated risk factors, survival and complications associated with EAD in a large liver transplant center in Latin America. Methods: Retrospective, unicenter, cohort, based on data from adult patients undergoing first deceased-donor liver transplant from January 2009 to December 2013. EAD was defined by one or more of the following: (i) bilirubin ≥10 mg/dL on postoperative day 7; (ii) international normalized ratio ≥1.6 on postoperative day 7, and (iii) alanine aminotransferase or aspartate aminotransferase > 2000 IU/L within the first seven days after transplant. Results: A total of 602 patients were included; of these 34.2% developed EAD. Donor risk factors were male (P = 0.007), age between 50 and 59 years (P = 0.034), overweight (P = 0.028) or grade I obesity (P = 0.012), sodium > 157 mmol/L (P = 0.002) and grade IV ischemia/reperfusion injury (P = 0.002). Cold ischemia time ≥10 h (P = 0.008) and warm ischemia time ≥40 min (P = 0.013) were the surgical factors. Male (P < 0.001) was the only recipient protective factor. Compared with the non-EAD group, patients with EAD were submitted to more reoperations (24.3% vs. 13.4%, P = 0.001) and had higher graft loss rates (37.9% vs. 21.2%, P < 0.001), with similar patient survival rates (P = 0.238). Conclusions: EAD risk factors are related to donor, surgical procedure and recipient. Donor risk factors for EAD were male, age between 50 and 59 years, donor overweight or grade I obesity, sodium > 157 mmol/L and grade IV ischemia/reperfusion injury. Cold ischemia time ≥10 h and warm ischemia time ≥40 min were the surgical risk factors. Male was the only recipient protective factor. Patients with EAD had higher reoperations and graft loss rates.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 423-429 . [Abstract] ( 65 ) [HTML 1KB] [PDF 0KB] ( 114 )

	430	Apaer S, Tuxun T, Li T, Aji T, Payiziwula J, Zhao JM, Shao YM, Wen H
		Compared efficacy of University of Wisconsin and histidine-tryptophan-ketoglutarate solutions in ex-situ liver resection and autotransplantation for end-stage hepatic alveolar echinococcosis patients
		Background: The University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the two most frequently used liver graft preservation fluids. The present study aimed to compare their efficacy in end-stage hepatic alveolar echinococcosis patients who underwent ex-situ liver resection and autotransplantation (ELRA). Methods: A total of 81 patients received ELRA from August 2010 to March 2018. They were allocated into UW ( n = 48) and HTK groups ( n = 33) based on the type of solutions used. Demographic and operational data were retrospectively analyzed. Primary outcomes included 90-day mortality, incidence of early graft loss, primary dysfunction, and postoperative complications. Results: Demographic and operational characteristics were similarly distributed in the two groups. No statistically significant differences were observed with regard to 90-day mortality (12.77% vs. 12.12%) and early graft loss rate (8.51% vs. 9.09%) between the two groups. Patients in the UW and HTK groups showed a primary dysfunction rate of 27.66% and 27.27%, respectively. The UW group exhibited a higher incidence tendency of biliary complications, albeit with no statistical significance. Conclusions: This is the largest cohort study comparing the efficacy of the UW and HTK organ-preserving solutions in end-stage hepatic alveolar echinococcosis patients in ELRA settings. UW and HTK solutions presented similar efficacy and safety. A randomized clinical trial with larger scale is needed for further investigation in future clinical applications.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 430-438 . [Abstract] ( 63 ) [HTML 1KB] [PDF 0KB] ( 95 )

ORIGINAL ARTICLES/Liver

	439	Mangieri CW, Strode MA, Bandera BC
		Improved hemostasis with major hepatic resection in the current surgical era
		Background: Major hepatic resection, predominantly performed for oncologic intent, is a complex procedure with the potential for severe intraoperative hemorrhage. The current surgical era has the ability to improve hemostasis throughout the performance of major hepatic resections which decreases blood transfusions and the detrimental effects associated with transfusion. We evaluated hemostasis and outcomes in the current surgical era of performing hepatic resections. Methods: Utilizing the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database all major hepatic resections performed between 2012 and 2016 were analyzed in regards to hemostasis. Hemostasis was evaluated by the need for and magnitude of blood transfusions. Additional perioperative variables (including operative time, length of hospital stay, and mortality rates) were analyzed to assess for outcomes with hemostasis. The NSQIP results were compared to previous publications involving major hepatic resections to detect improvement in hemostasis and outcomes in the current surgical era. Results: A total of 22777 major hepatic resections met the inclusion criteria for analysis in the NSQIP database. An additional 21198 cases were compiled within the selected publications for comparative analysis. The transfusion rate in the current surgical era was 13.3% versus 38.7% in the previous era ( P = 0.0001). When a transfusion was required in the current surgical era there was a two-fold reduction in the number of units transfused (1.5 U vs. 3.8 U, P = 0.0001). Statistically significant improvements in operative time and length of hospital stay were presented within the current surgical era ( P = 0.0001). When a transfusion was required there was an increased relative risk score of 7 for mortality (4.9% vs. 0.7%, P = 0.0001), however, improvement in mortality rates did not reach statistical significance across surgical eras (1.3% vs. 4.0%, P = 0.0001). Conclusions: The conduction of major hepatic resection in the current surgical era is more hemostatic. Correlated with improved hemostasis are better outcomes for both clinical and financial endpoints. These findings should encourage continued and increased performance of major hepatic resections.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 439-445 . [Abstract] ( 56 ) [HTML 1KB] [PDF 0KB] ( 103 )

	446	Li YD, Lv Z, Xie HY, Zheng SS
		Retinoblastoma binding protein 4 up-regulation is correlated with hepatic metastasis and poor prognosis in colon cancer patients
		Background: Retinoblastoma binding protein 4 (RBBP4) plays an essential role in the development of multiple cancers. However, its relationship with prognosis in colon cancer and colon cancer hepatic metas- tasis has not been elucidated. The aim of this study was to explore the relationship between RBBP4 expression and prognosis of colon cancer patients and to evaluate RBBP4 as a new prognostic marker in these patients. Methods: Eighty colon cancer patients underwent surgical resection of the colon were enrolled. Among them, forty colon cancer patients suffered with hepatic metastasis. The colon cancer tissues, para-colon cancer tissues, and hepatic metastatic cancer tissues were collected from the pathological department for further analysis. The expression of RBBP4 proteins was examined by immunohistochemistry and correlated with clinicopathological parameters. The Cancer Genome Atlas (TCGA) database was used to validate the expression and explore its relationship with clinical characteristics. Results: RBBP4 was up-regulated in the colon cancer tissues compared with the para-colon cancer tissues. The analysis of TCGA database verified the upregulation of RBBP4 in the colon cancer tissues and RBBP4 overexpression was correlated with nerve invasion and poor outcomes of chemotherapy. Moreover, the positive rate of RBBP4 expression in 40 colon cancer patients with hepatic metastasis was higher in the hepatic metastatic cancer tissues (39/40, 97.5%) than in the colon cancer tissues (26/40, 65.0%). Our clinicopathological analysis showed that RBBP4 expression was significantly correlated with vascular invasion, hepatic metastasis, and lymph node involvement (all P < 0.05). Additionally, the survival analysis demonstrated that RBBP4 over-expression was correlated with poor prognosis. Conclusions: RBBP4 was upregulated in the colon cancer. RBBP4 may be a novel predictor for poor prog- nosis of colon cancer and colon cancer hepatic metastasis.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 446-451 . [Abstract] ( 50 ) [HTML 1KB] [PDF 0KB] ( 109 )

	452	Cheung TT, Chok KSH, Chan ACY, Tsang SHY, Dai WC, Yau TCC, Kwong A, Lo CM
		Survival analysis of breast cancer liver metastasis treated by hepatectomy: A propensity score analysis for Chinese women in Hong Kong
		Background: Survival of patients with breast cancer liver metastasis is very poor. This study aimed to analyze the survival outcome of hepatectomy for this patient population. Methods: From January 1995 to December 2014, 2522 patients with liver cancer received hepatectomy at our hospital. Twenty-one of them, all female, received the operation for breast cancer liver metastasis. Performance was compared with patients with colorectal liver metastasis treated with hepatectomy after propensity score analysis in a ratio of 1:3. Results: Twenty-one patients received hepatectomy for breast cancer. After propensity score matching, 63 patients who had hepatectomy for colorectal cancer were selected for comparison. There was no significant difference in immediate or short-term outcomes between the two groups of patients in terms of operative time, blood loss and surgical morbidities. All patients with breast cancer had R0 resection. No hospital death occurred. After hepatectomy, the 1-, 3- and 5-year overall survival rates were 100.0%, 58.9% and 58.9% respectively in patients with breast cancer. The 1-, 3- and 5-year overall survival rates were 95.0%, 57.2% and 39.7% respectively in patients with colorectal cancer ( P = 0.572). On multivariate analysis, triple negative status was the only independent poor prognostic factor in breast cancer liver metastasis (OR = 6.411; 95% CI: 1.351–30.435; P = 0.019). Conclusions: Hepatectomy is a safe and effective way of treating breast cancer liver metastasis at experienced centers where multidisciplinary adjuvant treatments are available. It can be considered more frequently as part of the multidisciplinary care for this patient population.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 452-457 . [Abstract] ( 64 ) [HTML 1KB] [PDF 0KB] ( 99 )

	458	Jiang PX, Mao RC, Dong MH, Yu XP, Xun Q, Wang JY, Jing L, Qiang D, Zhang JM
		Exonuclease I and III improve the detection efficacy of hepatitis B virus covalently closed circular DNA ^Hot!
		Background: Hepatitis B virus covalently closed circular DNA (HBV cccDNA) is an important biomarker of hepatitis B virus infection. However, the current methods are not specific and sensitive. The present study aimed to develop a specific and sensitive assay method for the quantification of HBV cccDNA. Methods: Exonuclease I (Exo I) & Exonuclease III (Exo III) and specific primer probes are used in real-time PCR. The virus particles isolated from peripheral blood mononuclear cells were used as negative control and HBV1.3 recombinant plasmid 3.2 kb circular DNA fragment was used as positive control. The methods of cccDNA detection were evaluated in cell lines, plasmid, animal model, patient serum and liver biopsies. Results: A linear range of 10¹ –10⁷ copies/assay using specific primers for HBV cccDNA was established. HBV cccDNA were only detected in cell lines, animal model and liver tissue. It cannot be detected in serum samples. Intrahepatic HBV cccDNA level had good correlation with intrahepatic total HBV DNA level ( r = 0.765, P < 0.001). Conclusions: The real-time quantitative PCR is an effective and feasible method for sensitive and specific detection of low copy number of cccDNA. The novel detection method is fast, provides high sensitivity and specificity and can be used in clinical practice.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 458-463 . [Abstract] ( 61 ) [HTML 1KB] [PDF 0KB] ( 120 )

ORIGINAL ARTICLES/Biliary

	464	Zhu YJ, Xu Q, Shao MY, Cao XY,Wu ZR, Chen YW, Bu H, Shi YJ
		Decreased expression of HDAC8 indicates poor prognosis in patients with intrahepatic cholangiocarcinoma ^Hot!
		Background: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary tumor in the liver, and the rates of incidence and mortality are rapidly increasing globally. Histone deacetylase 8 (HDAC8) is a transcriptional regulator and is associated with tumorigenesis of several tumor types. This study aimed to evaluate the correlation between HDAC8 expression and clinicopathological parameters in ICC patients. Methods: ICC tissues and corresponding nonmalignant bile duct tissues were obtained from 60 patients. HDAC8 and Ki-67 expression were evaluated by immunohistochemistry staining. HDAC8 expression and the clinicopathological features and prognosis of the patients were analyzed. The mRNA level of HDAC8 in ICC was further analyzed using data from The Cancer Genome Atlas (TCGA). Results: The expression of HDAC8 were lower in ICC tissues (39/60, 65%) than in the corresponding nonmalignant bile duct tissues (54/60, 90%) (P = 0.001). Low HDAC8 expression in ICC was significantly associated with lymph node metastases (47.6% vs. 17.9%, P = 0.015). In addition, the positive cells rate of HDAC8 was statistically and negatively correlated with the Ki-67 index in ICC lesions (r = −0.7660, P < 0.001). Importantly, the overall survival rate and recurrence-free survival rate in ICC patients with low HDAC8 expression were lower than those with high HDAC8 expression (P = 0.008 and P = 0.011, respectively). Conclusions: Decreased HDAC8 expression in ICC is related to poor prognosis, and HDAC8 may be an independent prognostic indicator of ICC patients after curative resection.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 464-470 . [Abstract] ( 65 ) [HTML 1KB] [PDF 0KB] ( 106 )

ORIGINAL ARTICLES/Pancreas

	471	Liu X, Guo XZ, Li HY, Chen J
		KAI1 reverses the epithelial-mesenchymal transition in human pancreatic cancer cells
		Background: Epithelial-mesenchymal transition (EMT) plays an important role in pancreatic cancer (PC). In the present study, we investigated the effects of KAI1 gene overexpression on the EMT of human PC cell lines, MIA PaCa-2 and PACN-1. Methods: Plasmids overexpressing KAI1 and pCMV were transfected into MIA PaCa-2 and PACN-1 cells, respectively. After selection of differently transfected cells by G418, KAI1 protein levels were examined by Western blotting, and transfected cells were renamed as MIA PaCa-2-K, MIA PaCa-2-p, PACN-1-K and PACN-1-p. Wound healing and Transwell migration assays were then performed comparing the two groups of cells. EMT-related markers were analyzed by Western blotting. Results: The percentage of wound closure significantly decreased in MIA PaCa-2-K cells compared with MIA PaCa-2-p and MIA PaCa-2 cells after 24, 48 and 72 h ( P < 0.05). In PACN-1-K cells, the percentage of wound closure significantly decreased as well (P < 0.05). Numbers of invading MIA PaCa-2, MIA PaCa-2-p and MIA PaCa-2-K cells were determined as 48.0 ± 15.4, 50.0 ± 12.4, and 12.0 ± 3.8, respectively. The corresponding numbers of invading PACN-1, PACN-1-p and PACN-1-K cells were 29.0 ± 10.6, 31.0 ± 11.4, and 8.0 ± 4.2, respectively. KAI1 overexpression induced a significant upregulation of E-cadherin and also significant downregulation of Snail, vimentin, matrix metalloproteinase 2 (MMP2) and MMP9 (all P < 0.05) in PC cells. Conclusions: KAI1 reversed EMT-related marker expression and inhibited migration and invasion of PC cells. Thus, KAI1 might represent a novel potential therapeutic target for PC.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 471-477 . [Abstract] ( 55 ) [HTML 1KB] [PDF 0KB] ( 113 )

	478	Faraj W, Nassar H, Zaghal A, Mukherji D, Shamseddine A, Kanso M, Jaafar RF, Khalife M
		Pancreaticoduodenectomy in the Middle East: Achieving optimal results through specialization and standardization
		Background: Pancreaticoduodenectomy is a challenging surgical intervention that remains the corner- stone in the treatment of localized peri–ampullary pathologies. The concept of treatment standardization has been well-established in many high-volume centers in the world. Here, we present our experience in pancreaticoduodenectomy from 1994 to 2015. Methods: We performed a retrospective review of the medical charts of patients who underwent pan- creaticoduodenectomy at our institution. Data was entered to SPSS statistical software and analyzed. The Mann–Whitney U and Fisher’s exact tests were used to report statistical differences between groups. Results: Of the 370 patients who underwent pacreaticoduodenectomy, 300 were analyzed. The 1-, 3-, 5- and 10-year survival rates were 85%, 35%, 15%, and 7%, respectively with a 30-day mortality rate of 5.0% (15 patients). The median age of the patients was 61 (13–84) years, with 193 (64.3%) males and 107 (35.7%) females. The median operative time was 300 (130–570) min. The median postoperative length of hospital stay was 12 (5–76) days. Thirty-two patients required re-laparotomies; 10 for pancreatic leak, 7 for biliary leak and 15 for control of bleeding. Seventy-five (25.0%) patients developed pancreatic fistulae. Delayed gastric emptying was present in 31 (10.3%) patients. A significant improvement in surgical out- come was observed in cases done after 2008 which indicates the important role of specialized team in surgical management. Conclusions: The number of patients undergoing pancreaticoduodenectomy has been increasing annu- ally over the past twenty-two years in our institution with results comparable to published series from high-volume centers. Through standardization of surgical techniques and perioperative management car- ried out by a specialist team, our results continue to improve despite the increasing complexity of cases referred to our unit.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 478-483 . [Abstract] ( 56 ) [HTML 1KB] [PDF 0KB] ( 89 )

VIEWPOINTS

	484	Zhang HF, Xie ZY, Ouyang XX, Xu XW, Wang XY, Huang JR, Li LJ
		Accuracy of pipeline blood glucose monitoring in patients with severe liver injury undergoing artificial liver support system treatment
		Severe deterioration of liver function in patients can be characterized by coagulation disorders, jaundice, hepatic encephalopathy, ascites, and other symptoms. Severe liver injury can develop as acute liver failure, subacute liver failure, acute-on-chronic liver failure, or further worsening of end-stage liver disease [1] . Liver transplant is the standard therapy for patients with severe liver injury; however, it is hampered by a shortage of organ donors, complications caused by post-transplant immune rejection, and high cost [2] . Artificial liver support system (ALSS), based on the principle of temporarily replacing liver function, have been proposed as new therapeutic options to treat severe liver injury. In the past few decades, various types of ALSSs have been developed and applied to the treatment of severe liver injury [3] . These include plasma exchange (PE), the molecular adsorbent recirculating system (MARS), and the double plasma molecular adsorption system (DPMAS) [4] . Li’s artificial liver system (Li-ALSS), is a kind of ALSS that organically coupled by plasma exchange, plasma adsorption, and hemofiltration [5] . DPMAS is a part of Li-ALSS that combines two hemoperfusion columns to efficiently remove toxins from the plasma [6] .
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 484-487 . [Abstract] ( 66 ) [HTML 1KB] [PDF 0KB] ( 104 )

	488	Pizanias M, Kontis E, Prassas E, Srinivasan P, Prachalias A
		Surgical portosystemic shunts to facilitate major intrabdominal surgery
		The effective management of patients with chronic liver disease (CLD) and portal hypertension (PHT) has significantly prolonged their survival. Hence, there is an emerging number of patients who will require major elective intrabdominal surgery for reasons unrelated to their CLD (e.g., colorectal cancer). This group of patients represent high-risk surgical procedure due to their CLD, namely liver decompensation. To this end, alleviation of PHT is the most effective option of decreasing the risk of liver-related morbidity, either with surgical portosystemic shunts (SPS) or transjugular intrahepatic portosystemic shunt (TIPS). We present the short-term outcomes of a case series of 7 consecutive patients with established CLD and PHT, who underwent a concomitant SPS to facilitate major intraabdominal surgery. The short-term outcomes of SPS are presented and the current indications are reviewed.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 488-490 . [Abstract] ( 59 ) [HTML 1KB] [PDF 0KB] ( 92 )

	491	Covelli C, Parente P, Pepe F, Pisapia P, Fiordelisi F, Malapelle U
		Mismatch repair proteins and microsatellite instability in solid pseudopapillary neoplasm of the pancreas
		Solid pseudopapillary neoplasms (SPNs) are rare solid pancreatic tumors mainly affecting young women. Despite the high percentage of favorable prognosis, they are considered as low grade malignant neoplasms, and metastases occur in 5%−15% of patients. Almost all SPNs (95%) have somatic activating mutations in the β-catenin gene [1] . β-catenin plays a crucial role in cell proliferation and differentiation via Wnt signaling pathway and interacts with E-cadherin and α-catenin for the regulation of cell adhesion and growth [2] . Another relevant genetic alteration in pancreatic neoplasms is represented by the DNA mismatch repair deficiency (dMMR). dMMR is strongly associated with a microsatellite instability (MSI) status as a result of an alteration in the lengths of microsatellites due to deletion/insertion of repeating units in tumor DNA [3] . dMMR was observed in approximately 1%−2% of patients with pancreatic adenocarcinoma [4] . To date, the “gold standard” for the evaluation of protein integrity of MMR is immunohistochemistry (IHC), showing an analytical sensitivity > 90%, specificity of 100% and predictive value of 97% for microsatellite stability (MSS) and 100% for MSI [5] . The study aimed to investigate the expression of MMR proteins and the MSI status in pancreatic SPNs.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 491-492 . [Abstract] ( 57 ) [HTML 1KB] [PDF 0KB] ( 103 )

	493	Fang M, Yao M, Wang L, Yao DF
		Food for thought on hepatocellular carcinoma
		Hepatocellular carcinoma (HCC) is a serious public health problem worldwide [1] . Recently, Chen et al. [2] reported the observed survival and relative survival of leading cancer sites from a population-based cancer registry for 40 years in the inshore areas of the Yangtze River. HCC ranks the first among all malignancies and the poorest survival rate among cancer types in Qidong, China. The data indicated that the prevention and treatment of HCC still are far from satisfaction.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 493-494 . [Abstract] ( 60 ) [HTML 1KB] [PDF 0KB] ( 91 )

CLINICAL IMAGE

	495	Song TL, Chen H, Wang FR, Li YM
		Combined treatment for solid pseudopapillary tumor of the pancreas with liver metastasis
		Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic disease. Generally, it is considered a benign or low-grade malignant tumor. SPT of the pancreas with liver metastasis or invasion to adjacent organs is usually uncommon. We report a female patient who was diagnosed with SPT of the pancreas with liver metastasis. The patient received a series of treatments, including distal splenopancreatectomy, liver metastasis tumor resection, trans-arterial embolization (TAE) and high intensity focused ultrasound (HIFU) over the past 10 years.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 495-497 . [Abstract] ( 53 ) [HTML 1KB] [PDF 0KB] ( 102 )

	498	Pezzilli R, Mauloni PA, Pagano N
		Gossypibomas as a rare cause of common bile duct dilation
		Gossypibomas are any foreign bodies left inside the patient after an operation. It represents a diagnostic challenge in clinical practice because the clinical consequence may manifest in different forms immediately, months, or even years after the surgical procedure. For this reason we believe that it is worth reporting our case which was primarily diagnosed via endoscopic ultrasonography (EUS) and then treated endoscopically.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 498-500 . [Abstract] ( 50 ) [HTML 1KB] [PDF 0KB] ( 104 )

LETTERS TO THE EDITOR

	501	Braillon A
		IL-26 and the prognosis of hepatocellular carcinoma after resection
		I read with interest the article by Xi et al. that IL-26 is a novel prognostic factor for hepatocellular carcinoma (HCC) after resection [1] . I have some comments on it.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 501-501 . [Abstract] ( 55 ) [HTML 1KB] [PDF 0KB] ( 93 )

	502	Xi ZF, Jeong S, Xia Q
		Reply to: IL-26 and the prognosis of hepatocellular carcinoma after resection
		We thank Dr. Braillon for the thoughtful remarks regarding prognostic impact of interleukin (IL)−26 on patients with hepatocellular carcinoma (HCC) undergoing surgical resection [1]. This study drew a conclusion that relative high expression of IL-26 is an independent prognostic factor for HCC patients after resection. The raised concern regarding prospective confirmation is one of the most common underlying limitations of retrospective studies. In addition, a limited number of patients is an important determinant of power. Therefore, validation studies are warranted in the future.
		Hepatobiliary Pancreat Dis Int. 2019; 18(5): 502-502 . [Abstract] ( 52 ) [HTML 1KB] [PDF 0KB] ( 103 )

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