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Purpose: This study evaluated the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) calculator in predicting outcomes after hepatectomy for colorectal cancer (CRC) liver metastasis in a Southeast Asian population. Methods: Predicted and actual outcomes were compared for 166 patients undergoing hepatectomy for CRC liver metastasis identified between 2017 and 2022, using receiver operating characteristic curves with area under the curve (AUC) and Brier score. Results: The ACS-NSQIP calculator accurately predicted most postoperative complications (AUC > 0.70), except for surgical site infection (AUC = 0.678, Brier score = 0.045). It also exhibited satisfactory performance for readmission (AUC = 0.818, Brier score = 0.011), reoperation (AUC = 0.945, Brier score = 0.002), and length of stay (LOS, AUC = 0.909). The predicted LOS was close to the actual LOS (5.9 vs. 5.0 days, P = 0.985). Conclusion: The ACS-NSQIP calculator demonstrated generally accurate predictions for 30-day postoperative outcomes after hepatectomy for CRC liver metastasis in our patient population. [ABSTRACT FROM AUTHOR]

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]

Background: Epidemiological evidence suggests there are differences in gastroenteropancreatic neuroendocrine neoplasm (GEPNEN) among population groups. We aimed to contribute to the current evidence by evaluating the clinicopathological characteristics of GEPNEN in a multi-ethnic Asian group. Materials and Methods: This was a retrospective chart review of patients diagnosed with GEPNEN at a tertiary medical institution at Singhealth Outram Campus, Singapore, between 1995 and 2015. Results: Two hundred ninety-five patients were included in the evaluation, comprising Chinese (74.6%), Malay (4.4%), Indian (9.5%) and other (11.5%) ethnic backgrounds. The median age at diagnosis was 59 years; 52.5% were males. Distribution of disease stage at diagnosis was: localised (42.4%), regional (15.3%) and distant (38.0%). The three most common primary tumour sites were located in the pancreas (38.6%), rectum (19.7%) and stomach (9.5%), which varied significantly with ethnic background and age at diagnosis. Malay patients were younger (median 42 years) at diagnosis than Chinese (60 years). Patients with an appendiceal neuroendocrine neoplasm (NEN) (48 years) were younger compared to oesophageal NEN (66 years). Disease stage correlated with primary tumour site and grade (p < 0.001). Median overall survival (OS) for all GEPNEN was 10.2 years. Age at diagnosis, disease stage and grading were prognostic factors of OS in multivariable analyses. Conclusion: Our findings correspond with other studies that focus on GEPNEN incidences in Asian countries, with the pancreas, rectum and stomach being the most common primary tumour sites. Our findings suggest racial differences in primary tumour site and age at diagnosis. Further prospective population-based registries are required to understand these epidemiological differences. [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]

Introduction: The use of laparoscopic surgery for liver resection and the management of abdominal emergencies has been well established. However, the value of this technique for post-operative haemorrhage in liver resection has not been characterized. Case Description: We describe a case of post-operative haemorrhage following an elective totally laparoscopic liver resection that was treated with emergency hand-assisted laparoscopic haemostasis. Discussion: Emergency hand-assisted laparoscopic haemostasis in the setting of post-operative haemorrhage after laparoscopic liver resection is feasible and should be considered as a treatment option in suitable patients. [ABSTRACT FROM AUTHOR]

Background: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients.Methods: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy.Discussion: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients.Trial Registration: ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010. [ABSTRACT FROM AUTHOR]

Mechanisms underlying p53-mediated protection of the replicating genome remain elusive, despite the quintessential role of p53 in maintaining genomic stability. Here, we uncover an unexpected function of p53 in curbing replication stress by limiting PARP1 activity and preventing the unscheduled degradation of deprotected stalled forks. We searched for p53-dependent factors and elucidated RRM2B as a prime factor. Deficiency in p53/RRM2B results in the activation of an NRF2 antioxidant transcriptional program, with a concomitant elevation in basal PARylation in cells. Dissecting the consequences of p53/RRM2B loss revealed a crosstalk between redox metabolism and genome integrity that is negotiated through a hitherto undescribed NRF2-PARP1 axis, and pinpoint G6PD as a primary oxidative stress-induced NRF2 target and activator of basal PARylation. This study elucidates how loss of p53 could be destabilizing for the replicating genome and, importantly, describes an unanticipated crosstalk between redox metabolism, PARP1 and p53 tumor suppressor pathway that is broadly relevant in cancers and can be leveraged therapeutically., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Backgrounds/aims: In recent years, many minimally invasive techniques have been introduced to reduce the number of ports in laparoscopic cholecystectomy (LC), offering benefits such as reduced postoperative pain and improved cosmetic outcomes. ArtiSential ® is a new multi-degree-of-freedom articulating laparoscopic instrument that incorporates the ergonomic features of robotic surgery, potentially overcoming the spatial limitations of laparoscopic surgery. ArtiSential ® LC can be performed using only two ports. This study aims to compare the surgical outcomes of ArtiSential ® LC with those of single-fulcrum LC., Methods: This retrospective study compared ArtiSential ® LC and single-fulcrum LC among LCs performed for gallbladder (GB) stones at the same center, analyzing the basic characteristics of patients; intraoperative outcomes, such as operative time, estimated blood loss, and intraoperative GB rupture; and postoperative outcomes, such as length of hospital stay, incidence of postoperative complications, and postoperative pain., Results: A total of 88 and 63 patients underwent ArtiSential ® LC and single-fulcrum LC for GB stones, respectively. Analysis showed that ArtiSential ® LC resulted in significantly fewer cases of surgeries longer than 60 minutes (30 vs. 35 min, p = 0.009) and intraoperative GB ruptures (2 vs. 10, p = 0.007). In terms of postoperative outcomes, ArtiSential ® LC showed better results in the respective visual analog scale (VAS) scores immediately after surgery (2.59 vs. 3.73, p < 0.001), and before discharge (1.44 vs. 2.02, p = 0.01)., Conclusions: ArtiSential ® LC showed better results in terms of surgical outcomes, especially postoperative pain. Thus, ArtiSential ® LC is considered the better option for patients, compared to single-fulcrum LC.

Background: Limited liver resections (LLRs) for tumours located in the posterosuperior segments of the liver are technically demanding procedures. This study compared outcomes of robotic (R) and laparoscopic (L) LLR for tumours located in the posterosuperior liver segments (IV, VII, and VIII)., Methods: This was an international multicentre retrospective analysis of patients who underwent R-LLR or L-LLR at 24 centres between 2010 and 2019. Patient demographics, perioperative parameters, and postoperative outcomes were analysed; 1 : 3 propensity score matching (PSM) and 1 : 1 coarsened exact matching (CEM) were performed., Results: Of 1566 patients undergoing R-LLR and L-LLR, 983 met the study inclusion criteria. Before matching, 159 R-LLRs and 824 L-LLRs were included. After 1 : 3 PSM of 127 R-LLRs and 381 L-LLRs, comparison of perioperative outcomes showed that median blood loss (100 (i.q.r. 40-200) versus 200 (100-500) ml; P = 0.003), blood loss of at least 500 ml (9 (7.4 per cent) versus 94 (27.6 per cent); P < 0.001), intraoperative blood transfusion rate (4 (3.1 per cent) versus 38 (10.0 per cent); P = 0.025), rate of conversion to open surgery (1 (0.8 per cent) versus 30 (7.9 per cent); P = 0.022), median duration of Pringle manoeuvre when applied (30 (20-46) versus 40 (25-58) min; P = 0.012), and median duration of operation (175 (130-255) versus 224 (155-300); P < 0.001) were lower in the R-LLR group compared with the L-LLR group. After 1 : 1 CEM of 104 R-LLRs with 104 L-LLRs, R-LLR was similarly associated with significantly reduced blood loss and a lower rate of conversion to open surgery., Conclusion: Based on a matched analysis of well selected patients, both robotic and laparoscopic access could be undertaken safely with good outcomes for tumours in the posterosuperior liver segments., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)