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Hepatocellular carcinoma (HCC) is the third deadliest and sixth most common cancer in the world. Histone‐lysine N‐methyltransferase EHMT2 (also known as G9a) is a histone methyltransferase frequently overexpressed in many cancer types, including HCC. We showed that Myc‐driven liver tumours have a unique H3K9 methylation pattern with corresponding G9a overexpression. This phenomenon of increased G9a was further observed in our c‐Myc‐positive HCC patient‐derived xenografts. More importantly, we showed that HCC patients with higher c‐Myc and G9a expression levels portend a poorer survival with lower median survival months. We demonstrated that c‐Myc interacts with G9a in HCC and cooperates to regulate c‐Myc‐dependent gene repression. In addition, G9a stabilises c‐Myc to promote cancer development, contributing to the growth and invasive capacity in HCC. Furthermore, combination therapy between G9a and synthetic‐lethal target of c‐Myc, CDK9, demonstrates strong efficacy in patient‐derived avatars of Myc‐driven HCC. Our work suggests that targeting G9a could prove to be a potential therapeutic avenue for Myc‐driven liver cancer. This will increase our understanding of the underlying epigenetic mechanisms of aggressive tumour initiation and lead to improved therapeutic and diagnostic options for Myc‐driven hepatic tumours. [ABSTRACT FROM AUTHOR]

Early tumor recurrence after curative surgical resection poses a great challenge to the clinical management of hepatocellular carcinoma (HCC). We conducted whole genome expression microarrays on 64 primary HCC tumors with clinically defined recurrence status and cross‐referenced with RNA‐seq data from 18 HCC tumors in the Cancer Genome Atlas project. We identified a 77‐gene signature, which is significantly associated with early recurrent (ER) HCC tumors. This ER‐associated signature shows significant enrichment in genes involved in cell cycle pathway. We performed receiver operating characteristic (ROC) analysis to evaluate the prognostic biomarker potential of these 77 genes and Pearson correlation analysis to identify 11 close clusters. The one gene with the best area under the ROC curve in each of the 11 clusters was selected for validation using reverse‐transcription quantitative PCR in an independent cohort of 24 HCC tumors. NUF2 was identified to be the minimal biomarker sufficient to discriminate ER tumors from LR tumors. NUF2 in combination with liver cirrhosis could significantly improve the detection of ER tumors with an AUROC of 0.82 and 0.85 in the test and validation cohort, respectively. In conclusion, NUF2 in combination with liver cirrhosis is a promising prognostic biomarker for early HCC recurrence. What's new? More than 60% of hepatocellular carcinomas (HCC) will recur after surgical resection. Patients who suffer early recurrence have a poorer prognosis than those whose tumors recur later. New biomarkers for early HCC recurrence are thus urgently needed. In this study, the authors found that the combination of liver cirrhosis plus increased expression of a single gene, NUF2, can predict early recurrence. NUF2 is thus a promising, novel prognostic biomarker that may improve the clinical management of HCC after curative resection. [ABSTRACT FROM AUTHOR]

Background: Recurrent pyogenic cholangitis (RPC) has a high risk of disease recurrence. We present our experience with RPC and examine the factors associated with disease recurrence. Methods: We performed a retrospective review of all patients with RPC treated at two tertiary institutions between January 1990 and December 2013. Patients with liver atrophy and/or abscess were categorized as being associated with parenchymal disease (PD). Results: We studied 157 patients with a median age of 59.0 (interquartile range (IQR): 47.0–70.0) years and a median follow‐up duration of 71.0 (IQR: 26.0–109.0) months. There were 64 (40.8%) and 93 (59.2%) patients with and without associated PD, respectively. Disease recurrence rate was 43.9% in our overall cohort through the course of follow‐up. Surgical treatment was an independent prognostic factor for decreased disease recurrence risk (hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.18–0.87, P = 0.021). Stratified analysis revealed that liver resection was prognostic for lower risk of disease recurrence among patients with PD (HR 0.38, 95% CI 0.15–0.94, P = 0.036), while biliary bypass was prognostic for lower risk of disease recurrence among patients without PD (HR 0.30, 95% CI 0.15–0.61, P = 0.001). The overall post‐operative complication rate among surgically treated patients was 31.1%, and the presence of bilobar stones was found to be independently associated with higher odds of post‐operative complications (odds ratio 3.51, 95% CI 1.26–9.81, P = 0.017). Conclusion: Surgical treatment is associated with decreased recurrence risk in RPC, but with significant post‐operative morbidity. Where surgery is deemed appropriate, patients with and without PD are likely to benefit from liver resection and biliary bypass, respectively. [ABSTRACT FROM AUTHOR]

Introduction: Intussusception in adults is increasingly diagnosed on cross-sectional imaging with a lack of clear recommendations on management. The presence of an underlying lead point is a key to guiding management as its absence can predict spontaneous resolution. We studied adult patients with computed tomography (CT) diagnosed intussusception formulate a clinical scoring system to predict the risk of an underlying lead point.Methodology: We performed a retrospective review of all adult patients who underwent CT scans of the abdomen and pelvis in our institution between 2001 and 2014. Independent associations of an underlying lead point were derived following multivariable analysis, from which a clinical scoring system was developed.Results: We studied 140 patients. In multivariable analysis, six factors were found to be independently associated with the presence of an underlying lead point, namely gender, abdominal pain, CT evidence of colonic involvement, CT evidence of a lead point, distal diameter ≥27 mm and minimum wall thickness ≥3 mm. A nine-point clinical scoring system was developed, with a cutoff score of four or higher yielding a sensitivity and specificity of 0.75 and 0.81, respectively.Conclusion: Our clinical scoring system provides a quantitative tool to predict the likelihood of an underlying lead point in CT-diagnosed intussusception in adults to help guide management. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal stromal tumours ( GISTs) represent the most common mesenchymal tumour of the gastrointestinal tract. Although the efficacy of targeted therapy cannot be over-emphasized, surgery remains the only curative primary treatment for patients with localized disease. The median size of GIST at diagnosis is approximately 5-7 cm; however, it is not uncommon for tumours to be as large as 30-40 cm and involving multiple viscera. Methods Data were retrospectively collected from patients with GISTs treated at the Singapore General Hospital and the National Cancer Centre Singapore over a 15-year period. Standard resection of GIST without any additional organ removal was termed as a single organ resection ( SOR). If the tumour was adjacent to another organ, necessitating the removal of more than one organ, the procedure was defined as a multivisceral resection ( MVR). We aim to evaluate the role of MVR in the management of large GISTs. Results A total of 187 patients underwent curative surgery for GIST between January 2000 and January 2014. Of the 187 patients, 40 (21%) underwent MVR whereas 147 (79%) had SOR. Patients in the MVR group had significantly larger tumour sizes ( P < 0.001) yet R0 and R1 resection was achieved in all patients, and no intra-peritoneal rupture was reported. On comparison of MVR versus SOR groups, there was no significant difference in in-hospital morbidity and mortality. Conclusion MVR may be required to achieve negative margins in patients with large GISTs, and can be performed with acceptable morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal stromal tumours ( GISTs), despite complete surgical cytoreduction, are associated with recurrence rates of up to 50% at 2 years. At recurrence, tyrosine kinase inhibitor ( TKI) therapy is recommended, conferring a survival of up to 55 months. Several studies have shown that patients with TKI-responsive recurrent GIST benefit from surgery. However, no studies have compared upfront surgery versus TKI alone. Methods Data were retrospectively collected from patients with recurrent GIST treated at Singapore General Hospital and National Cancer Centre Singapore over a 12-year period. Our primary end points were disease-free and overall survival ( OS). Results A total of 186 patients underwent curative surgery for GIST between January 2000 and June 2012. Fifty-six (30%) patients experienced recurrence, of which 30 (54%) had resectable recurrent disease. Twenty-four patients underwent upfront surgery for their recurrence while the remaining six patients opted for non-surgical management. The median OS for all patients with recurrent GIST was 5.3 years (95% confidence interval ( CI) 3.2-8.4). It was not reached for patients who underwent curative surgery for their recurrence, and was 3.9 years (95% CI 2.4-7.0) for patients who had palliative TKI and conservative management. There were significant differences in OS and disease-specific survival between patients who underwent curative surgery for recurrence compared with those who had not. Conclusion Our study shows that upfront surgery is a reasonable treatment strategy for selected patients with recurrent GIST. [ABSTRACT FROM AUTHOR]

Objective Hypertrophy of the contralateral liver lobe after treatment with yttrium-90 (90Y) microspheres has recently been reported. This study aimed to quantify left hepatic lobe hypertrophy after right-sided radioembolization for hepatocellular carcinoma ( HCC) and to identify pretreatment predictive factors of hypertrophy in an Asian population. Methods A retrospective review of patients with inoperable HCC undergoing selective internal radiation treatment ( SIRT) with 90 Y microspheres at a single institution from January 2008 to January 2012 was performed. Only patients who had treatment delivered via the right hepatic artery alone were included. Results In all, 17 patients fulfilling the study criteria were identified. The mean percentage of left-lobe hypertrophy was 34.2% ± 34.9% (range 19.0-106.5%) during a median of 5-month follow-up. Patients with hepatitis B were found to experience a significantly greater degree of hypertrophy than those with hepatitis C or alcoholic liver cirrhosis. There were no cases of acute liver failure after the administration of SIRT in this study and none of the patients developed disease in the contralateral lobe over the study period. Conclusions Administration of unilobar SIRT to the right liver lobe in patients with HCC resulted in a significant degree of contralateral left lobe hypertrophy. Patients with hepatitis B experienced a greater degree of hypertrophy than those with hepatitis C or alcoholic liver cirrhosis. [ABSTRACT FROM AUTHOR]