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Objectives: To study the feasibility of using surgical procedure manager (SPM), a digital checklist platform, to standardise surgical steps of open hernia repair and monitor the operative performance. Methodology: A retrospective study on all open mesh repair of inguinal hernia under local anaesthesia from September 2019 to November 2021 at the Prince of Wales Hospital was performed. The operative outcomes of patients having operations with or without the use of SPM were compared. Procedures using SPM had operation steps shown as a digital checklist inside the theatre. The time used for each surgical step was recorded and analysed. The operative performance of the surgeons was analysed by observing the trend of the mean operation time over time. Results: A total of 123 patients were recruited, of which 52 were using the SPM. The median age of patients was 75 (range 49–93) years. A decreasing trend in the mean operation time for dissection, mesh placement, wound closure and total operation time was observed in surgeries using SPM. There was no significant difference in the operation time, theatre time, total length of stay, blood loss and readmission rate between the SPM and non‐SPM groups. The proportion of basic surgical trainees as coached surgeons in the SPM group was significantly higher (SPM = 52% vs non‐SPM = 28%, P =.07). Conclusions: The use of SPM did not significantly prolong the operation time and produce comparable operative outcomes in open hernia repair. It provided the additional advantage of standardising operation steps and monitoring the performance of surgical trainees during their training. [ABSTRACT FROM AUTHOR]

Enhancing through epigenetics: A challenge for cancer immunotherapy is the need to turn cold, immune cell–excluded tumors into hot, inflamed tumors. Here, Yang et al. investigated the role of histone deacetylase 8 (HDAC8) in maintaining immune cell–excluded tumors. The authors showed that selective pharmacological inhibition of HDAC8 changed the epigenetic landscape of hepatocellular carcinoma cells, leading to production of T cell–recruiting chemokines. Treatment of hepatocellular carcinoma–bearing mice with the selective HDAC8 inhibitor resulted in increased infiltration of CD8+ T cells. Further, treatment with the HDAC8 inhibitor and immune checkpoint blockade led to enhanced control of tumors with no evidence of toxicity. Thus, epigenetic reprogramming used in combination with immunotherapy may be a promising approach for treating hepatocellular carcinomas and other immunologically cold tumors. Insufficient T cell infiltration into noninflamed tumors, such as hepatocellular carcinoma (HCC), restricts the effectiveness of immune-checkpoint blockade (ICB) for a subset of patients. Epigenetic therapy provides further opportunities to rewire cancer-associated transcriptional programs, but whether and how selective epigenetic inhibition counteracts the immune-excluded phenotype remain incompletely defined. Here, we showed that pharmacological inhibition of histone deacetylase 8 (HDAC8), a histone H3 lysine 27 (H3K27)–specific isozyme overexpressed in a variety of human cancers, thwarts HCC tumorigenicity in a T cell–dependent manner. The tumor-suppressive effect of selective HDAC8 inhibition was abrogated by CD8+ T cell depletion or regulatory T cell adoptive transfer. Chromatin profiling of human HDAC8-expressing HCCs revealed genome-wide H3K27 deacetylation in 1251 silenced enhancer-target gene pairs that are enriched in metabolic and immune regulators. Mechanistically, down-regulation of HDAC8 increased global and enhancer acetylation of H3K27 to reactivate production of T cell–trafficking chemokines by HCC cells, thus relieving T cell exclusion in both immunodeficient and humanized mouse models. In an HCC preclinical model, selective HDAC8 inhibition increased tumor-infiltrating CD8+ T cells and potentiated eradication of established hepatomas by anti–PD-L1 therapy without evidence of toxicity. Mice treated with HDAC8 and PD-L1 coblockade were protected against subsequent tumor rechallenge as a result of the induction of memory T cells and remained tumor-free for greater than 15 months. Collectively, our study demonstrates that selective HDAC8 inhibition elicits effective and durable responses to ICB by co-opting adaptive immunity through enhancer reprogramming. [ABSTRACT FROM AUTHOR]

Serologic and molecular surveillance of serum collected from 152 suspected scrub typhus patients in Myanmar revealed Orientia tsutsugamushi of genotypic heterogeneity. In addition, potential co-infection with severe fever with thrombocytopenia syndrome virus was observed in 5 (3.3%) patients. Both scrub typhus and severe fever with thrombocytopenia syndrome are endemic in Myanmar. [ABSTRACT FROM AUTHOR]

Background: The advantages of radiofrequency ablation (RFA) over hepatectomy as a treatment for early-stage hepatocellular carcinoma (HCC) include reduced morbidity and more rapid recovery. Although minimally invasive surgery provides similar benefits, few studies have compared the long-term oncological outcomes of these techniques. This study aimed to compare the outcomes of minimally invasive hepatectomy (MIH) and RFA. Methods: Patients who underwent MIH or RFA for HCC between January 2005 and January 2015 were included in a propensity score matching analysis. Only patients who underwent minimally invasive procedures for small HCC were included. Baseline clinical and laboratory parameters were retrieved from the hospital database and analyzed. Results: Two hundred and twenty-five patients underwent MIH or RFA for HCC during the study period. Propensity score matching yielded 59 patient-pairs. The complication rates did not differ statistically between the 2 groups (p = 0.309). However, MIH provided significantly better overall (p = 0.005) and disease-free survival outcomes (p < 0.001) than RFA. Conclusions: Compared with RFA, MIH provided better long-term survival outcomes in patients with early-stage HCC, with no increase in the incidence of complications. When feasible, MIH should be considered a first-line treatment for this patient population. [ABSTRACT FROM AUTHOR]

Aim: Reduction in the surgical mortality has been observed in Hong Kong public hospitals after the implementation of the Surgical Outcomes Monitoring and Improvement Program (SOMIP). The aim of the present study was to identify factors and strategies that allow surgeons to improve their outcome after the implementation of the SOMIP. Patients and Methods: A qualitative study among surgeons in SOMIP‐participating hospitals using semistructured interviews was performed, with questions focused on knowledge of the SOMIP, comments on SOMIP methodology and actions taken by hospitals to drive quality improvement. Results: Fifteen surgeons from five public hospitals in Hong Kong were recruited. The provision of objective data, culture change, surgeons' motivation to improve, advice from external reviewers, leadership and support from administration were identified as factors driving outcome improvement after the implementation of the SOMIP. Most surgeons strongly agreed that SOMIP can be used as a quality improvement tool and there was a need to disclose hospital results. Conclusions: A risk‐adjusted, outcome‐based, quality improvement program could provide objective data as feedback to surgical units and benchmark with peers. Together with the driving force from public reporting, change in culture, appropriate resource allocation and service planning, improvement in the structure, process and outcome can be achieved. [ABSTRACT FROM AUTHOR]

Inflammatory pseudotumour (IPT) is a spectrum of lesions which mimic malignancies in various organs. Preoperative diagnosis is often challenging. In this case report, we present two rare cases of Epstein‐Barr virus (EBV) associated IPTs and discuss the clinico‐pathological characteristics of these two entities. [ABSTRACT FROM AUTHOR]

Squalene epoxidase is a therapeutic target in hepatocellular carcinoma arising from nonalcoholic fatty liver disease. Antifungal drug may help fight cancer: The rates of nonalcoholic fatty liver disease are increasing with the rising prevalence of obesity and are associated with an increase in the incidence of hepatocellular carcinoma. By studying the mechanism of hepatocellular carcinoma arising in the setting of nonalcoholic fatty liver disease, Liu et al. discovered a role for squalene epoxidase, a metabolic enzyme involved in cholesterol biosynthesis. Using a combination of human cancer cells and mouse models of disease, the authors examined the pathway by which squalene epoxidase promotes the development of hepatocellular carcinoma and identified terbinafine, a clinically approved antifungal drug, as a potential intervention. Nonalcoholic fatty liver disease (NAFLD)–induced hepatocellular carcinoma (HCC) is an emerging malignancy in the developed world; however, mechanisms that contribute to its formation are largely unknown, and targeted therapy is currently not available. Our RNA sequencing analysis of NAFLD-HCC samples revealed squalene epoxidase (SQLE) as the top outlier metabolic gene overexpressed in NAFLD-HCC patients. Hepatocyte-specific Sqle transgenic expression in mice accelerated the development of high-fat, high-cholesterol diet–induced HCC. SQLE exerts its oncogenic effect via its metabolites, cholesteryl ester and nicotinamide adenine dinucleotide phosphate (NADP+). Increased SQLE expression promotes the biosynthesis of cholesteryl ester, which induces NAFLD-HCC cell growth. SQLE increased the NADP+/NADPH (reduced form of NADP+) ratio, which triggered a cascade of events involving oxidative stress–induced DNA methyltransferase 3A (DNMT3A) expression, DNMT3A-mediated epigenetic silencing of PTEN, and activation of AKT-mTOR (mammalian target of rapamycin). In human NAFLD-HCC and HCC, SQLE is overexpressed and its expression is associated with poor patient outcomes. Terbinafine, a U.S. Food and Drug Administration–approved antifungal drug targeting SQLE, markedly inhibited SQLE-induced NAFLD-HCC cell growth in NAFLD-HCC and HCC cells and attenuated tumor development in xenograft models and in Sqle transgenic mice. Suppression of tumor growth by terbinafine is associated with decreased cholesteryl ester concentrations, restoration of PTEN expression, and inhibition of AKT-mTOR, consistent with blockade of SQLE function. Collectively, we established SQLE as an oncogene in NAFLD-HCC and propose that repurposing SQLE inhibitors may be a promising approach for the prevention and treatment of NAFLD-HCC. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatocellular carcinoma (HCC) is a complicated disease with low survival rate partially due to frequent recurrence and no efficient therapy. Promoter hypermethylation of tumor suppressor genes has been demonstrated as one of the molecular mechanisms contributing to tumorigenesis and progression in HCC. This study aims to investigate regulation of NKAPL expression by promoter methylation and its clinical relevance as a biomarker for HCC.Methods: We measured mRNA expression of NKAPL in 5 HCC cell lines and a cohort of 62 pairs of primary HCC tumor and their adjacent non-cancer liver tissues. NKAPL protein expression on HCC cell lines and clinical samples was assessed by Western blot and immunohistochemistry, respectively. Association analyses between NKAPL expression and clinicopathologic characteristics in the cohort were conducted. Methylation statuses of NKAPL promoter in 18 pairs of tumor and adjacent non-tumor HCC samples were studied using methylation-specific PCR. Biological functions of NKAPL in HCC were investigated by ectopic expression of NKAPL in HCC cells, and cell viability and cell cycle analyses were performed.Results: Our present study showed suppressed expression and promoter hypermethylation are common events in HCC. Demethylation experiment in HCC cells demonstrated that the NKAPL expression was regulated by promoter methylation. In addition, high methylation level of NKAPL and its low expression predict poor outcome. Furthermore, ectopic expression of NKAPL in the HCC cells inhibited cell growth.Conclusions: Our findings suggest that methylation of NKAPL is a frequent event and is a potential prognosis biomarker in HCC. [ABSTRACT FROM AUTHOR]

Aim To achieve better outcomes, nonoperative management (NOM) and damage control surgery (DCS) are now recommended for traumatic liver injury. The aim of the present study was to review the outcomes of patients suffering from liver trauma and to determine the factors affecting the outcomes, with emphasis on NOM and DCS. Patients and Methods This was a retrospective cohort study for liver trauma patients from a single centre. The outcomes were compared between two equal consecutive periods: period A (2001-2007) and period B (2008-2014). Results There were 116 patients, with a mean age of 38.1 years and a male predominance (61.2 per cent). Approximately 57 per cent of patients suffered from grade III or higher liver injury. The mean Injury Severity Score (ISS) was 32.3. The 90-day mortality was 20.7 per cent. During period B, the 90-day mortality was significantly lowered (6/56 vs 18/60, P = 0.010) with less liver operations (13/56 vs 26/60, P = 0.022) and more hepatic angiography ± embolization (7/56 vs 0/60, P = 0.005). The proportion of DCS was similar, but more hepatectomies were performed in period B (4/13 vs 0/26, P = 0.009). Multivariate analysis revealed that ISS grade, age and sex were predictors for 90-day mortality. Conclusions Reduced mortality was seen in traumatic liver injury accomplished by increased NOM, but not DCS. [ABSTRACT FROM AUTHOR]

Background and Aim Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post-hepatectomy liver failure. Methods A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post-hepatectomy liver failure according to the International Study Group of Liver Surgery definition. Results A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post-hepatectomy liver failure. ( P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high-grade post-hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor. Conclusions Liver stiffness measurement using Fibroscan is good to predict high-grade post-hepatectomy liver failure especially in patients without right lobe tumor. [ABSTRACT FROM AUTHOR]

We would like to report a case of acute appendicitis complicated with superior mesenteric venous (SMV) thrombophlebitis. A 61‐year‐old gentleman presented with abdominal pain and high fever with elevated white cell count and slightly deranged liver function and clotting profile. Besides features of acute appendicitis, a thrombus in superior mesenteric vein was demonstrated on computed tomography (CT). Patient was treated with emergency laparoscopic appendectomy, a course of antibiotics and subcutaneous enoxaparin. CT 2 months after operation showed features of resolving SMV thrombophlebitis. Mesenteric venous thrombophlebitis is difficult to diagnose as the clinical presentation is often nonspecific and it depends on the site and timing of thrombus formation. Such rare complication has to be suspected if the patient presents late or when there were high fever and deranged liver function. Prompt appendectomy and antibiotics therapy remain the essential components of treatment for acute appendicitis. The need of additional anticoagulation therapy and its optimal duration for SMV thrombophlebitis remains unclear. Nevertheless, the use of anticoagulation therapy should be weighed against the risk of bleeding complication. [ABSTRACT FROM AUTHOR]

Aim Studies comparing the efficacy of radiofrequency ablation ( RFA) in terms of overall survival, disease-free survival and local recurrence in recurrent hepatocellular carcinoma ( HCC) are limited. We carried out the present study to compare the survival of recurrent HCC after RFA with that of first-occurrence HCC. Patients and Methods A total of 170 patients with HCC smaller than 5 cm who received RFA in a tertiary academic hospital were recruited. Clinical data were prospectively collected, reviewed and compared between recurrent and first-occurrence HCC groups. Patients who received RFA for post-ablation recurrent HCC were excluded. Results There was no significant difference in the complication, incomplete ablation, recurrence and survival rates between the recurrent HCC and the first-occurrence HCC groups. The tumour size in the recurrent HCC group was significantly smaller than that in the first-occurrence group (1.8 vs 2.5 cm), and the recurrent HCC group had a significantly higher proportion of Child's A cirrhosis. Conclusions When detected and treated early, the overall survival of recurrent HCC treated RFA was comparable to that of first-occurrence HCC. The advantages of RFA, especially when percutaneous route is feasible, over hepatectomy should be extended to recurrent HCC in suitable cases. [ABSTRACT FROM AUTHOR]

Aim The aim of the present study was to assess patients' understanding of their informed consent to surgery preoperatively. Appropriate completeness of essential items in the written consent form was also verified. Patients and Methods An audit was conducted from March to May 2013 at a university teaching hospital. All participants were adult surgical patients. Operations were confined to major category on elective basis performed under general anaesthesia. The first part of the audit consisted of a structured questionnaire with five questions concerning their understanding and perception of the surgery. In the second part of the audit, the completeness of all fundamental items entered into the standardized written consent form was verified. Results A total of 100 surgical patients were studied, with a median age of 61 years (range: 22-89). A total of 99 per cent of participants could state the correct name and site of the procedure, and 92 per cent could state the mode of anaesthesia. Only 39 per cent of patients received an information leaflet regarding the operation, of which 80 per cent claimed this could enhance their understanding of the procedure. Only 70 per cent of them could recall the potential surgical risks. Most essential items were completed in the consent forms. Witnesses were involved only in 24 per cent of cases. Illegible surgeons' handwriting was observed in 6 per cent of consent documents. Conclusions Most patients could understand the nature and site of the operation they were going to receive. The provision of relevant information to our patients preoperatively was insufficient. Patients had limited recall of the potential surgical risks. There is room for improvement in the present informed consent process. [ABSTRACT FROM AUTHOR]

Aim Evaluation of the prevalence of delayed gastric emptying ( DGE) post-operatively is thwarted by an inconsistency in DGE definition. The aim of the present study was to evaluate the incidence and underlying risk factors of DGE after pancreaticoduodenectomy (PD), employing the International Group of Pancreatic Surgery ( ISGPS) consensus definition. Patients and Methods Patient demographics, operative details, clinical course and pathology of 95 consecutive patients who underwent PD at a tertiary academic institution were analysed. Results The overall incidence of DGE was 32.6 per cent, and those of grades A, B and C were 18.9 per cent, 5.3 per cent and 8.4 per cent, respectively. DGE was associated with longer post-operative length of stay (17 days vs 13 days, P = 0.016). With increasing DGE severity, there was a statistically-significant increase in the presence of post-operative pancreatic fistula greater than grade A ( P = 0.033) and the post-operative length of stay ( P = 0.020). Post-operative pleural effusion ( P = 0.020) and increased number of lymph nodes resected ( P = 0.014) are significant independent risk factors for DGE. Conclusions The ISGPS definition and grading systems for DGE are applicable and correlate well with clinical course. An association between more extensive lymphatic dissection and DGE is noted. [ABSTRACT FROM AUTHOR]

Objective To describe a service delivery model and report the baseline characteristics of patients investigated by a non-invasive approach for ketamine-associated uropathy. Patients and Methods This was a cross-sectional study in a prospective cohort of patients who attended their first visit and underwent non-invasive investigations at a dedicated centre to treat ketamine-associated uropathy in Hong Kong from December 2011 to July 2013. Data on demographics, illicit ketamine use, symptoms scores and voiding function parameters at baseline were prospectively collected. Differences between active abusers and ex-abusers, and risk factors for the most symptomatic group were investigated by univariate and multivariate analysis. Results In all, 318 patients completed the non-invasive assessment at their first visit and were eligible for inclusion. In all, 174 were female and the mean ( sd) age of the entire cohort was 24.4 (3.1) years. Patients had used ketamine for a mean ( sd) period of 81 (36) months. The mean ( sd) ketamine use per week was 18.5 (15.8) g. In all, 214 patients were active abusers while 104 were ex-abusers but had persistent lower urinary tract symptoms. The mean ( sd) voided volume, bladder capacity, and bladder emptying efficiency were 111.5 (110) mL, 152.5 (126) mL and 73.3 (26.9)%, respectively. The ex-abusers had a lower symptom score (19.3 vs 24.1; P < 0.001), a larger voided volume (126 vs 85 mL; P < 0.001), and a larger bladder capacity (204.8 vs 126.7 mL; P < 0.001) compared with active abusers. Multivariate analysis found female gender was associated with a higher symptom score (odds ratio [ OR] 2.39; 95% confidence interval [ CI] 1.35-4.23; P = 0.003) and a smaller voided volume ( OR 1.9; 95% CI 1.1-3.3; P = 0.02). Ketamine taken (g/week) was another risk factor for a higher symptom score ( OR 1.03; 95% CI 1.01-1.05; P = 0.002). Status of ex-abuser was the only protective factor associated with fewer symptoms, larger voided volume and bladder capacity. Conclusions An effective service model for recruiting patients with ketamine-associated uropathy is possible. With such a service model as a platform, further prospective studies are warranted to investigate the appropriate choice of treatment for this new clinical entity. [ABSTRACT FROM AUTHOR]

Four and a Half LIM protein 2 (FHL2) is a LIM domain only protein that is able to form various protein complexes and regulate gene transcription. Recent findings showed that FHL2 is a potential tumor suppressor gene that was down-regulated in hepatocellular carcinoma (HCC). Moreover, FHL2 can bind to and activate the TP53 promoter in hepatic cells. In this study, the activity of the two promoters of FHL2, 1a and 1b, were determined in the human embryonic kidney cell line HEK293 and the activation of these two promoters by p53 was investigated. Our results showed that the 1b promoter has a higher activity than the 1a promoter in HEK 293 cells but the 1a promoter is more responsive to the activation by p53 when compared with the 1b promoter. The regulation of FHL2 by p53 was further confirmed in liver cells by the overexpression of p53 in Hep3B cells and the knockdown of p53 in HepG2 cells. Combining promoter activity results of truncated mutants and predictions by bioinformatics tools, a putative p53 binding site was found in the exon 1a of FHL2 from +213 to +232. The binding between the p53 protein and the putative p53 binding site was then validated by the ChIP assay. Furthermore, the expression of FHL2 and TP53 were down-regulated in majority of HCC tumour samples (n = 41) and significantly correlated (P = 0.026). Finally, we found that the somatic mutation 747 (G→T), a hot spot mutation of the TP53 gene, is potentially associated with a higher expression of FHL2 in HCC tumour samples. Taken together, this is the first in-depth study about the transcriptional regulation of FHL2 by p53. [ABSTRACT FROM AUTHOR]

Objective: This study examined the risk factors associated with failure of enhanced recovery protocol after major hepatobiliary and pancreatic (HBP) surgery. Setting and participants: A retrospective cohort of 194 adult patients undergoing major HBP surgery at a university hospital in Hong Kong was followed up for 30 days. The patients were from a larger cohort study of 736 consecutive adults with preoperative urinary cotinine concentration to examine the association between passive smoking and risk of perioperative respiratory complications and postoperative morbidities. Outcome measures: The primary outcome was failure of enhanced recovery protocol. This was defined as a composite measure of the following events: intensive care unit (ICU) stay more than 24 h after surgery, unplanned admission to ICU within 30 days after surgery, hospital readmission, reoperation and mortality. Results: There were 25 failures of enhanced recovery after HBP surgery (12.9%, 95% CI 8.5% to 18.4%). After adjusting for elective ICU admission, smokers (relative risk (RR ) 2.21, 95% CI 1.10 to 4.46), high preoperative alanine transaminase/glutamic-pyruvic transaminase (RR 3.55,95% CI 1.68 to 7.49) and postoperative morbidities (RR 2.69, 95% CI 1.30 to 5.56) were associated with failures of enhanced recovery in the generalised estimating equation risk model. Compared with those managed successfully, failures stayed longer in ICU (median 19 vs 25 h, p<0.001) and in hospital for postoperative care (median 7 vs 13 days, p=0.003). Conclusions: Smokers and patients having high preoperative alanine transaminase/glutamic-pyruvic transaminase concentration or have a high risk of postoperative morbidities are likely to fail enhanced recovery protocol in HBP surgery programmes. [ABSTRACT FROM AUTHOR]

Abstract: The putative tumor suppressor Mst1, when cleaved to its 36kDa cleaved form, amplifies apoptotic signals. We found that Mst1 was predominantly expressed in its full-length form in 76% (17/25 cases) of hepatocellular carcinoma (HCC) tumors. Mst1 cleavage was basically absent in HCC cells. Ectopic full-length Mst1 expression increased the growth of HCC cells by 55–80% within 3days after transfection. Expression of exogenous NORE1B, a tumor suppressor commonly lost in HCC tumors (∼56% of our cohort), was sufficient to suppress the growth promotion of full-length Mst1. Hence, Mst1 exhibits a growth promoting activity in HCC cells upon NORE1B downregulation. [Copyright &y& Elsevier]

Hepatitis viral B x protein (HBx), a hepatocarcinogen, is frequently mutated. Hypoxia influences the growth of HCC and also the sensitivity of tumor cells to treatments. We aimed to test the role of HBx and acute hypoxia in the efficacy of chemotherapy. In this study, we established 4 Chang liver cell lines with the full-length HBx (HBx), the first 50 amino acids of N-terminal HBx (HBx/50), the last 104 amino acids of C-terminal HBx (HBx/51) and empty vector (CL), respectively. MTT and TNUEL assays were used to assess cell viability and apoptosis respectively. Western blot was used to determine the expression of relevant proteins. Results showed that among 4 cell lines, doxorubicin was most effective in decreasing the viability and enhancing apoptosis in HBx/51 cells, while HBx/50 cells were most resistant to the treatment. Cells in hypoxia were more susceptible to doxorubicin than cells in normoxia. Hypoxia facilitated the Bid cleavage especially in HBx/51 cells via phosphorylating p38 MAPK. p38 MAPK inhibitor significantly reduced the tBid level and increased cell viability. In conclusion, N-terminal HBx and C-terminal HBx function differentially in their ability to regulate cell growth, with the former being promotive but the latter being inhibitory. The acute hypoxia may overcome the HBx-induced resistance and facilitate the chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: The timing of laparoscopic cholecystectomy for acute cholecystitis remains controversial. This article reviews the latest evidence for the timing of laparoscopic cholecystectomy in the management of acute cholecystitis. Methodology: Trials comparing early laparoscopic cholecystectomy (ELC; carried out within 1 week of onset of symptoms) versus delayed laparoscopic cholecystectomy (DLC; carried out at least 6 weeks after symptoms settled) for acute cholecystitis were identified from Ovid Medline, Cochrane Library and PubMed database. Only meta-analyses and randomized clinical trials were reviewed. Results: A total of seven prospective randomized trials including 670 patients and four meta-analyses were reviewed. ELC was superior to DLC in terms of a shorter hospital stay without any significant difference in perioperative mortality and morbidity. Conclusions: Current evidence supports ELC as the preferred treatment strategy for acute cholecystitis. It allows a shorter hospital stay, but shares similar operative morbidity, mortality and conversion rate as DLC. [ABSTRACT FROM AUTHOR]

Aim: To review the evidence in using inflow occlusion during liver resection. Other strategies to minimize the untoward effects of inflow occlusion will also be discussed. Methods: Randomized trials evaluating the use of inflow occlusion in hepatectomy and strategies to minimize its associated adverse effects were reviewed in this article. Recent experience showing comparable operative outcomes without the use of portal clamping was also described. Results: Results from randomized trials and meta-analyses were not conclusive on the benefits of routine inflow occlusion during liver resection. Intermittent inflow occlusion and ischaemic preconditioning had been found to be effective in reducing ischaemic-reperfusion injury to remnant liver. With refined operative techniques and better instruments, routine inflow occlusion in liver resection can now be safely avoided. Conclusion: Vascular inflow occlusion is an important armamentarium during liver resection, but it should not be used indiscriminately. With refined techniques and better instruments, hepatectomy can be performed safely without the need for routine inflow occlusion. [ABSTRACT FROM AUTHOR]

Background: The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods: Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results: Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion: Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare patients who underwent single-site access laparoscopic appendectomy (SSALA) to those who underwent conventional three-port laparoscopic appendectomy (TPLA) in a case-controlled manner. Methods: Consecutive patients who underwent SSALA for suspected acute appendicitis between April and September 2009 were retrospectively compared to those who underwent TPLA between January and December 2008 in a case-controlled manner. The patients were matched for age, gender, and pathological findings. The main outcome measurements included postoperative recovery, morbidities, and mortalities. Results: During the study period, a total of 30 patients underwent SSALA and these were matched with 60 TPLA patients. There were no significant differences in the mean operative time, hospital stay, and 30-day morbidity rate between the two groups. None of the patients required conversion. Two patients with significant contamination and abscess collection noted during SSALA required a relaparotomy for peritoneal lavage and adhesiolysis due to prolonged ileus. Conclusions: SSALA is feasible and the perioperative outcome was comparable to that of TPLA. However, future prospective studies will need to evaluate whether SSALA can adequately tackle patients with significant peritoneal contamination. [ABSTRACT FROM AUTHOR]

SummaryAim:Recently, we have demonstrated that silymarin has a comparable pharmaceutical activity as Phyllanthus urinariaextract when used to rescue mice from acetaminophen-induced acute liver injury. In the present study, we further compared the therapeutic action of silymarin with N-acetyl cysteine (commonly used in clinical practice for emergency treatments) as a rescuer in mice after administering a lethal dose of acetaminophen for 24 h. Methods:Acute liver injury was induced in the treatment groups by intraperitoneally administered acetaminophen at a dose of 550 mg/kg body weight on day 1. The control group received an equal volume of physiological saline intraperitoneally. From day 2 to 4, the treatment groups received various doses of silymarin or N-acetyl cysteine orally once daily, while the control group and the acetaminophen group received an equal volume of water orally. The mortality rate was recorded in all groups. On day 5, all mice were sacrificed for examination. Results:Silymarin greatly improved the counteracting effects on mortality rate as compared to N-acetyl cysteine. Conclusion:Silymarin should be further considered as an antidote for patients with acetaminopheninduced acute hepatic injury and delayed treatment. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Intrahepatic cholangiocarcinoma (ICC) is a rare tumor of the liver. The diagnosis and treatment of it are difficult. The present study reviewed the diagnostic pathways and operative results for ICC. Methods: A retrospective analysis was made of the clinical presentation, diagnostic pathways, and operative results of 20 patients with ICC who underwent hepatectomy from 1997 to 2004 in our institute. Results: The patients were predominantly female (female : male = 15:5), and ranged in age from 41 to 74 years (median 59.8). Abdominal pain was the main presenting symptom, and hepatomegaly was the commonest physical sign. Diagnosis relied mainly on ultrasound or computed tomography. Without biopsy, only two patients were correctly diagnosed with ICC before surgery. The median size of the tumor was 6 cm (range 1.6–12 cm). Major hepatectomy was carried out in 80% of patients. The operative mortality and morbidity were 15% and 40%, respectively. The median follow up was 18.3 months. Thirteen patients (65%) had recurrences at one or more sites, including, in decreasing frequency, the liver, abdominal lymph node, lung, bone, or skin. The median survival was 17.3 months and the 1-year, 3-year, and 5-year survival rates were 60%, 45%, and 10%, respectively. Conclusions: The poor survival of patients with ICC was mainly due to the delay in diagnosis and the aggressive nature of the disease. The diagnosis of ICC relies on a high index of suspicion as there is no reliable tumor marker and imaging results are usually inconclusive. Radical hepatectomy remains the only chance of cure for ICC. The role of lymph node dissection, liver transplantation, and adjunctive chemotherapy in the treatment of patients with ICC remains to be determined. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate and compare the biodistribution properties of three transarterial Lipiodol-based therapeutic regimens in human hepatocellular carcinoma (HCC). In this prospective study with 13 patients randomly allocated to one of three study groups, each of the patients received transcatheter intra-arterial administration into a solitary HCC with one of three different Lipiodol-based formulations: Lipiodol-ethanol mixture (LEM; Group A), Lipiodol alone (Group B), and Lipiodol and gelatin pledgets (Group C). With the use of radioactive iodine-131-labeled Lipiodol, each group was assessed for (1) pattern of Lipiodol accumulation in the lungs within the first 2 weeks as evaluated by single-photon emission computed tomography and (2) decomposition of Lipiodol formulation within the first 2 weeks as evaluated by radioactivity detected in peripheral blood and urine. The degree of Lipiodol retention in the tumor within the first 4 weeks was evaluated with CT. No statistically significant difference in Lipiodol accumulation in the lungs was detected among the three groups. However, the peak accumulation in the lungs was delayed 3 days for Group A compared to Groups B and C. The degree of Lipiodol retention within the tumor in Group A was significantly greater than that in Groups B and C on day 14 (p = 0.014) and day 28 (p = 0.013). This study showed that LEM is associated with a greater embolic effect in intrahepatic HCC at 4 weeks, and a comparable degree of lung shunting and decomposition rates, compared with ethanol-free Lipiodol formulations. [ABSTRACT FROM AUTHOR]

Pancreatic pseudocyst is an amylase-rich peri-pancreatic fluid collection devoid of epithelial lining. Occasionally, it cannot be differentiated from cystic neoplasm of pancreas and resections are required. We report a case of pancreatic pseudocyst masquerading cystic neoplasm treated with distal pancreatectomy. The investigation strategy and management of cystic lesions of the pancreas are also discussed. [ABSTRACT FROM AUTHOR]

Background: The survival benefit of surveillance for hepatocellular carcinoma (HCC) is controversial. Aim: We aimed to examine the survival benefit of HCC surveillance in chronic viral hepatitis. Methods: Survivals of HCC patients related to chronic viral hepatitis from the Hepatology Clinic (surveillance group) were compared with those referred from other hospitals/clinics (no-surveillance group). Lead-time and length-time biases were adjusted based on tumour volume doubling times. Results: Among 579 patients (91% hepatitis B), 472 (82%) patients had HCC and 79 (17%) of these patients were referred from the surveillance programme. HCC was smaller (4.2 vs. 7.7 cm; P<0.001) and fewer in numbers (2.6 vs. 3.8, P=0.03) in the surveillance group vs. the no-surveillance group. Treatment by surgery (20 vs. 10%, P=0.007) and local ablative therapy (46 vs. 19%, P<0.001) were more frequent in the surveillance group than that in the no-surveillance group. The median survival of the surveillance group (88 weeks) was significantly longer than that of the no-surveillance group (26 weeks) ( P<0.001). The adjusted cumulative survival at 2 years was significantly longer in the surveillance group if the tumour volume doubling time was <90 days ( P=0.0352). Conclusions: HCC surveillance can improve the survival of patients with chronic viral hepatitis B. [ABSTRACT FROM AUTHOR]

Three patients who presented with scrotal swelling within a few days of inguinal herniorrhaphy are reported. Ultrasonography scans performed in these patients all demonstrated features suspicious of recurrence of hernia. One patient underwent surgical exploration, which revealed only a scrotal haematoma without evidence of recurrent hernia. The other two patients were managed conservatively because clinically the swellings were regarded to be more compatible with haematoma. Both patients had subsequent resolution of the scrotal swelling with no clinical evidence of recurrence of hernia on follow-up. It is concluded that sonographic diagnosis of recurrence of hernia shortly after inguinal herniorrhaphy can occasionally be misleading. [ABSTRACT FROM AUTHOR]

Objective: Eradication of Helicobacter pylori is effective in preventing ulcer relapse after simple repair of perforated duodenal ulcers. However, when and how the H. pylori status should be determined remains unclear. The study investigated the role of early endoscopic follow up in managing patients with simple omentopexy for duodenal ulcer perforation. Patients and Method: Patients below the age of 75 years who had simple repair of perforated duodenal ulcer were recruited. They were given a 4-week course of H2 receptor antagonist upon discharge and advised to return for a follow-up endoscopy at 8 weeks after operation. During endoscopic examination, ulcer healing and other gastroduodenal pathology were noted. Random biopsies were taken from the antrum and body of the stomach for determination of H. pylori infection. Results: In a 30-month period, 112 patients were admitted with perforated duodenal ulcers. The perforation was repaired by either laparoscopic (n = 41) or open method ( n = 71). Eleven patients died during hospitalization. Of the 101 patients who recovered, 16 were lost to follow up. Nine patients were considered unfit for endoscopy as a result of medical comorbidities. Among the 76 patients who attended the follow-up endoscopy, 47 were shown to have H. pylori infection (61.8%). Active duodenal ulcers were found in 15 patients, significant erosions in five patients and severe duodenitis in seven patients. Patients infected by H. pylori had a significantly higher proportion of persistent duodenal pathology compared with the uninfected patients (23/47 vs 4/29; P = 0.003). Multivariate analysis revealed that smoking and H. pylori infection were the two independent factors predicting persistent duodenal lesions. Conclusion: Patients treated with simple closure for duodenal ulcer perforation are recommended to have their H. pylori status determined by early follow-up endoscopy, and an eradication regimen should be prescribed to those who are... [ABSTRACT FROM AUTHOR]

Comments on a study which aimed to evaluate the usefulness of the Boey scoring system and the Acute Physiology and Chronic Health Evaluation II score in predicting the mortality and morbidity of patients operated on for perforated peptic ulcers. Results of the study; Preoperative risk factors in predicting conversion rate; Mortality and morbidity after risk stratification.

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations by: methylation-specific PCR (MSP) to determine the methylation status of the p16 promoter region; comparative multiplex PCR to detect homozygous deletion; PCR – SSCP and DNA sequencing analysis to identify mutation of the p16 gene. We found high frequency of hypermethylation of the 5′ CpG island of the p16 gene in 30 of 48 cases (62.5%) of HCC tumors. Moreover, homozygous deletion at p16 region were present in five of 48 cases (10.4%); and missense mutation were detected in three of 48 cases (6.3%). The overall frequency of p16 alterations, including homozygous deletion, mutation and hypermethylation, in HCC tumors was 70.8% (34 of 48 cases). These findings suggest that: (a) the inactivation of the p16 is a frequent event in HCC; (b) the p16 gene is inactivated by multiple mechanisms including homozygous deletion, promoter hypermethylation and point mutation; (c) the most common somatic alteration of the p16 gene in HCC is de novo hypermethylation of the 5′ CpG island; and (d) in contrast to other studies, high frequency of genomic alterations are not uncommon in the 9p21 of the p16 gene. Our results strongly suggest that the p16 gene plays an important role in the pathogenesis of HCC. [ABSTRACT FROM AUTHOR]

Recent literature on laparoscopic inguinal hernia repair (LIHR) has shown that laparoscopic hernioplasty is associated with reduced postoperative pain and wound infection, and an earlier return to normal daily activities. The technique of LIHR is still evolving. We descibe our technique and experience in performing laparoscopic hernioplasty using a contoured three-dimensional mesh without the application of endoscopic staples. [ABSTRACT FROM AUTHOR]

Henoch-Schonlein purpura (HSP) is characterized by vasculitis affecting small vessels. Typically, it would involve the skin, gut, and kidney and is associated with arthraglia or arthritis. In children, HSP may be complicated by intussusception, perforation and infarction of the gut, requiring surgical intervention. However, in adults, surgical intervention is seldom necessary. Sometimes, HSP may cause diagnostic confusion and results in unnecessary operation in children. This case report documents an adult patient who suffered from HSP who presented with acute abdomen that caused diagnostic confusion. In conclusion, high index of suspicion and early diagnosis of HSP may avoid unnecessary surgery. [ABSTRACT FROM AUTHOR]

The article presents a case study of laparoscopic removal of cystic duct stump stone in a 51-year-old Chinese man who was referred for recurrent right upper pain after cholecystectomy. He underwent endoscopic retrograde cholangiopancreatography (ERCP), which revealed a cystic duct remnant stone compressing onto the bile duct. He then underwent laparascopic surgery to remove the stone following cannulation.

The article presents a case study of a 55-year-old gentleman with duct-type intra-ductal papillary mucinous neoplasm at the pancreatic tail. Topics discussed include diagnosis of a well circumscribed lobulated cystic lesion in the tail of pancreas, use of robot-assisted laparoscopic spleen-preserving distal pancreatectomy, and emphasis on spleen preservation for reducing the lifetime risk of post-splenectomy.

The article presents a case study of 27-year-old man suffering from hepatitis B carrier along with an 8-cm right lobe liver mass that was detected on computed tomography during evaluation of his recurrent pneumothorax. Topics include Castleman's disease, hepatectomy and coexistence of a rare lymphoid disease in a patient with hepatocellular carcinoma.

The article presents a case study of an 80-year-old woman presented with diabetes mellitus, ischaemic heart disease and acute cholangitis. It mentions that computed tomography revealed the presence of Mirizzi syndrome with multiple gallstones and contracted gallbladder. It also mentions that the patient underwent robotic subtotal cholecystectomy and duodenum has been separated from the gallbladder with dissection.

Reactive nodular fibrous pseudotumor ( RNFP) is a rare, benign, reactive lesion to antecedent abdominal surgery or trauma. In the presents study, we report a case of a 54-year-old woman who developed a mass at the hepatic hilum after laparoscopic cholecystectomy. The mass was excised completely in two separate operations, and histopathological examination confirmed RNFP. The clinical significance of the disease is discussed. [ABSTRACT FROM AUTHOR]