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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.

This systematic review and meta-analysis aimed to evaluate the impact of prospective payment systems (PPSs) on cholecystectomy. A comprehensive literature review was conducted, examining studies published until December 2023. The review process focused on identifying research across major databases that reported critical outcomes such as length of stay (LOS), mortality, complications, admissions, readmissions, and costs following PPS for cholecystectomy. The studies were specifically selected for their relevance to the impact of PPS or the transition from fee-for-service (FFS) to PPS. The study analyzed six papers, with three eligible for meta-analysis, to assess the impact of the shift from FFS to PPS in laparoscopic and open cholecystectomy procedures. Our findings indicated no significant changes in LOS and mortality rates following the transition from FFS to PPS. Complication rates varied and were influenced by the diagnosis-related group categorization and surgeon cost profiles under episode-based payment. There was a slight increase in admissions and readmissions, and mixed effects on hospital costs and financial margins, suggesting varied responses to PPS for cholecystectomy procedures. The impact of PPS on cholecystectomy is nuanced and varies across different aspects of healthcare delivery. Our findings indicate a need for adaptable, patient-centered PPS models that balance economic efficiency with high-quality patient care. The study emphasizes the importance of considering specific surgical procedures and patient demographics in healthcare payment reforms.

Background: This study evaluated the cost-effectiveness of open, laparoscopic, and robotic liver resection., Methods: A comprehensive literature review and Bayesian network meta-analysis were conducted. Surface under cumulative ranking area values, mean difference, odds ratio, and 95% credible intervals were calculated for all outcomes. Cluster analysis was performed to determine the most cost-effective clustering approach. Costs-morbidity, costs-mortality, and costs-efficacy were the primary outcomes assessed, with postoperative overall morbidity, mortality, and length of stay associated with total costs for open, laparoscopic, and robotic liver resection., Results: Laparoscopic liver resection incurred the lowest total costs (laparoscopic liver resection versus open liver resection: mean difference -2,529.84, 95% credible intervals -4,192.69 to -884.83; laparoscopic liver resection versus robotic liver resection: mean difference -3,363.37, 95% credible intervals -5,629.24 to -1,119.38). Open liver resection had the lowest procedural costs but incurred the highest hospitalization costs compared to laparoscopic liver resection and robotic liver resection. Conversely, robotic liver resection had the highest total and procedural costs but the lowest hospitalization costs. Robotic liver resection and laparoscopic liver resection had a significantly reduced length of stay than open liver resection and showed less postoperative morbidity. Laparoscopic liver resection resulted in the lowest readmission and liver-specific complication rates. Laparoscopic liver resection and robotic liver resection demonstrated advantages in costs-morbidity efficiency. While robotic liver resection offered notable benefits in mortality and length of stay, these were balanced against its highest total costs, presenting a nuanced trade-off in the costs-mortality and costs-efficacy analyses., Conclusion: Laparoscopic liver resection represents a more cost-effective option for hepatectomy with superior postoperative outcomes and shorter length of stay than open liver resection. Robotic liver resection, though costlier than laparoscopic liver resection, along with laparoscopic liver resection, consistently exceeds open liver resection in surgical performance., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Minimally invasive surgery (MIS) for limited resections for pancreatic uncinate lesions is not widely performed but can adequately treat benign or low-grade malignant lesions. The aim of this study was to evaluate the short-term outcomes of MIS-limited pancreatic resections for patients with suspected pancreatic neuroendocrine tumours (PNETs)., Patients and Methods: This was a retrospective study of six consecutive patients who underwent MIS for PNET within a single institution between 2017 and 2022., Results: Six patients underwent limited pancreas-preserving MIS of the uncinate process (uncinectomy or enucleation), of which two were performed through the robotic approach and four through laparoscopic approach. The median operation time was 212.5 (175-338.75) min, and the median blood loss was 50 (50-112.5) ml. The median post-operative hospital length of stay was 5.5 (3.75-11.5) days. Two patients (33.3%) had major post-operative morbidities (Clavien-Dindo ≥Grade 3). There were no open conversions or post-operative mortalities. Five patients had histologically proven Grade 1 neuroendocrine tumours. One was T2 and four were T1., Conclusions: This study suggests that limited MIS resections of pancreatic uncinate PNETs are a feasible procedure with good patient outcomes. It offers a safe alternative to radical surgical resections like pancreatoduodenectomies in selected patients with low-grade malignant or benign tumours., (Copyright © 2024 Copyright: © 2024 Journal of Minimal Access Surgery.)

Background: This study compared the cost-effectiveness of open (ODP), laparoscopic (LDP), and robotic (RDP) distal pancreatectomy (DP)., Methods: Studies reporting the costs of DP were included in a literature search until August 2023. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area (SUCRA) values, mean difference (MD), odds ratio (OR), and 95% credible intervals (CrIs) were calculated for outcomes of interest. Cluster analysis was performed to examine the similarity and classification of DP approaches into homogeneous clusters. A decision model-based cost-utility analysis was conducted for the cost-effectiveness analysis of DP strategies., Results: Twenty-six studies with 29,164 patients were included in the analysis. Among the three groups, LDP had the lowest overall costs, while ODP had the highest overall costs (LDP vs. ODP: MD - 3521.36, 95% CrI - 6172.91 to - 1228.59). RDP had the highest procedural costs (ODP vs. RDP: MD - 4311.15, 95% CrI - 6005.40 to - 2599.16; LDP vs. RDP: MD - 3772.25, 95% CrI - 4989.50 to - 2535.16), but incurred the lowest hospitalization costs. Both LDP (MD - 3663.82, 95% CrI - 6906.52 to - 747.69) and RDP (MD - 6678.42, 95% CrI - 11,434.30 to - 2972.89) had significantly reduced hospitalization costs compared to ODP. LDP and RDP demonstrated a superior profile regarding costs-morbidity, costs-mortality, costs-efficacy, and costs-utility compared to ODP. Compared to ODP, LDP and RDP cost $3110 and $817 less per patient, resulting in 0.03 and 0.05 additional quality-adjusted life years (QALYs), respectively, with positive incremental net monetary benefit (NMB). RDP costs $2293 more than LDP with a negative incremental NMB but generates 0.02 additional QALYs with improved postoperative morbidity and spleen preservation. Probabilistic sensitivity analysis suggests that LDP and RDP are more cost-effective options compared to ODP at various willingness-to-pay thresholds., Conclusion: LDP and RDP are more cost-effective than ODP, with LDP exhibiting better cost savings and RDP demonstrating superior surgical outcomes and improved QALYs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aims to compare the outcomes of high-volume, medium-volume, and low-volume hospitals performing hepatic resections using a network meta-analysis., Methods: A literature search until June 2023 was conducted across major databases to identify studies comparing outcomes in high-volume, medium-volume, and low-volume hospitals for liver resection. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area values, odds ratio, and mean difference with 95% credible intervals were reported for postoperative mortality, failure-to-rescue, morbidity, length of stay, and hospital costs., Results: Twenty studies comprising 248,707 patients undergoing liver resection were included. For the primary mortality outcome, overall and subgroup analyses were performed: group I: high-volume = 5 to 20 resections/year; group II: high-volume = 21 to 49 resections/year; group III: high-volume ≥50 resections/year. Results demonstrated a significant association between hospital volume and mortality (overall-high-volume versus medium-volume: odds ratio 0.66, 95% credible interval 0.49-0.87; high-volume versus low-volume: odds ratio 0.52, 95% credible interval 0.41-0.65; group I-high-volume versus low-volume: odds ratio 0.34, 95% credible interval 0.22-0.50; medium-volume versus low-volume: odds ratio 0.56, 95% credible interval 0.33-0.92; group II-high-volume versus low-volume: odds ratio 0.67, 95% credible interval 0.45-0.91), as well as length of stay (high-volume versus low-volume: mean difference -1.24, 95% credible interval -2.07 to -0.41), favoring high-volume hospitals. No significant difference was observed in failure-to-rescue, morbidity, or hospital costs across the 3 groups., Conclusion: This study supports a positive relationship between hospital volume and surgical outcomes in liver resection. Patients from high-volume hospitals experience superior outcomes in terms of lower postoperative mortality and shorter lengths of stay than medium-volume and low-volume hospitals., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background & Aims: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance., Methods: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer., Results: Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5)., Conclusions: The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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.)

Objective: We aimed to prognosticate survival after surgical resection of HCC stratified by stage with amalgamation of the modified Barcelona Clinic Liver Cancer (BCLC) staging system and location of tumour., Methods: This single-institutional retrospective cohort study included patients with HCC who underwent surgical resection between 1st January 2000 to 30th June 2016. Participants were divided into 6 different subgroups: A-u) Within MC with Unilobar lesions; A-b) Within MC + Bilobar lesions; B1-u) Out of MC + within Up-To-7 + Unilobar lesions; B1-b) Out of MC + within Up-to-7 + Bilobar lesions; B2-u) Out of MC + Out of Up-To-7 + Unilobar lesions; B2-b) Out of MC + Out of Up-To-7 + Bilobar lesions. A separate survival analysis was conducted for solitary HCC lesions according to three subgroups: A-S (Within MC); B1-S (Out of MC + within Up-To-7); B2-S (Out of MC + out of Up-To-7)., Results: A total of 794 of 1043 patients with surgical resection for HCC were analysed. Groups A-u (64.6%), A-b (58.4%) and B1-u (56.2%) had 5-year cumulative overall survival (OS) rates above 50% after surgical resection and median OS exceeding 60 months (P = 0.0001). The 5-year cumulative recurrence-free survival rates (RFS) were 40.4% (group A-u), 38.2% (group A-b), 36.3% (group B1-u), 24.6% (group B2-u), and 7.3% (group B2-b)(P=0.0001). For solitary lesions, the 5-year OS for the subgroups were A-S (65.1%), B1-S (56.0%) and B2-S (47.1%) (P = 0.0003). Compared to A-S, there was also a significant trend towards relatively poorer OS as the lesion sizes increased in B1-S (HR 1.46, 95% CI 1.03-2.08) and B2-S (HR 1.65, 95% CI 1.25-2.18)., Conclusion: We adopted a novel approach combining the modified BCLC B sub-classification and dispersion of tumour to show that surgical resection in intermediate stage HCC can be robustly prognosticated. We found that size prognosticates resection outcomes in solitary tumours., Competing Interests: Pierce K.H. Chow declares the following conflicts of interest: Consulting or Advisory Role: Sirtex Medical, Bayer, Roche, New B Innovation, MSD, BTG PLC, Eisai, Abbott, IQVIA, Genentech, L.E.K Consulting, AstraZeneca, Guerbet, Ipsen, OncoSil, Eisai, Worrell, COR2ED and Bristol-Myers Squibb; Speakers’ Bureau: Sirtex Medical; Leadership Role and Stock Ownership: AVATAMED (Chief Medical Officer); and Research Funding: Roche, Sirtex Medical, New B Innovation, IQVIA, Genentech, Perspectum, AMiLi, MiRXES and Engine Biosciences. The authors report no other conflicts of interest in this work., (© 2022 Wee et al.)

Background: Pancreatic adenocarcinoma (PDAC) is highly lethal. Surgery offers the only chance of cure, but 5-year overall survival (OS) after surgical resection and adjuvant therapy remains dismal. Adjuvant trials were mostly conducted in the West enrolling fit patients. Applicability to a general population, especially Asia has not been described adequately., Aim: We aimed to evaluate the clinical outcomes, prognostic factors of survival, pattern, and timing of recurrence after curative resection in an Asian institution., Methods and Results: The clinicopathologic and survival outcomes of 165 PDAC patients who underwent curative resection between 1998 and 2013 were reviewed retrospectively. Median age at surgery was 62.0 years. 55.2% were male, and 73.3% had tumors involving the head of pancreas. The median OS of the entire cohort was 19.7 months. Median OS of patients who received adjuvant chemotherapy was 23.8 months. Negative predictors of survival include lymph node ratio (LNR) of >0.3 (HR = 3.36, P = .001), tumor site involving the body or tail of pancreas (HR = 1.59, P = .046), presence of perineural invasion (PNI) (HR = 2.36, P = .018) and poorly differentiated/undifferentiated tumor grade (HR = 1.86, P = .058). The median time to recurrence was 8.87 months, with 66.1% and 81.2% of patients developing recurrence at 12 months and 24 months respectively. The most common site of recurrence was the liver., Conclusion: The survival of Asian patients with resected PDAC who received adjuvant chemotherapy is comparable to reported randomized trials. Clinical characteristics seem similar to Western patients. Hence, geographical locations may not be a necessary stratification factor in RCTs. Conversely, lymph node ratio and status of PNI ought to be incorporated., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Purpose: NUF2 has been implicated in multiple cancers recently, suggesting NUF2 may play a role in the common tumorigenesis process. In this study, we aim to perform comprehensive meta-analysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA)., Materials and Methods: RNA-sequencing data in 31 cancer types in the TCGA data and 11 independent datasets were used to examine NUF2 expression. Silencing NUF2 using targeting shRNAs in hepatocellular carcinoma (HCC) cell lines was used to evaluate NUF2's role in HCC in vitro and in vivo., Results: NUF2 up-regulation is significantly observed in 23 out of the 31 cancer types in the TCGA datasets and validated in 13 major cancer types using 11 independent datasets. NUF2 overexpression was clinically important as high NUF2 was significantly associated with tumor stages in eight different cancers. High NUF2 was also associated with significantly poorer patient overall survival and disease-free survival in eight and six cancers, respectively. We proceeded to validate NUF2 overexpression and its negative association with overall survival at the protein level in an independent cohort of 40 HCC patients. Compared to the non-targeting controls, NUF2 knockdown cells showed significantly reduced ability to grow, migrate into a scratch wound and invade the 8 μm porous membrane in vitro. Moreover, NUF2 knockdown cells also formed significantly smaller tumors than control cells in mouse xenograft assays in vivo., Conclusion: NUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies.

Introduction: Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS)., Method: We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC)., Results: Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC., Conclusion: The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics., Competing Interests: Pierce K.H. Chow declares the following conflicts of interest: Editorial Board Member of Liver Cancer, Consulting or Advisory Role: Sirtex Medical, Bayer, Roche, New B Innovation, MSD, BTG PLC, Eisai, Abbott, IQVIA, Genentech, L.E.K Consulting, Astra Zeneca, Guerbet, Ipsen, OncoSil Medical, and Bristol-Myers Squibb; Speakers' Bureau: Sirtex Medical; and Research Funding: Sirtex Medical (Inst), New B Innovation (Inst), and IQVIA (Inst)., (Copyright © 2021 by S. Karger AG, Basel.)

Hepatic artery (HA) complications after liver transplant (LT) can lead to biliary complications, graft failure, and mortality. Although microsurgery has been established to improve anastomotic outcomes, it prolongs surgical time and has not reached widespread adoption at all transplant centers. We investigated the incidences of arterial, biliary complications and outcomes after using microsurgery to anastomose HA during LT. Retrospective cohort of consecutive LT performed from 2006 to 2018 was reviewed for operative details and postoperative outcomes. Cox-regression models were used to investigate the relationship between variables and outcomes. Eighty (62.5%) LTs (Group 1) were performed without and compared with 48 (Group 2) with microsurgical anastomosis of HA. Both groups were comparable in terms of arterial and biliary anastomoses performed. Incidence of early HA thrombosis was similar (6.2% vs 2.1%, P = .28). Group 2 had lower incidence of short- and long-term arterial complications, especially amongst living donor liver transplantations (LDLT) (5.3% vs 35.0%, P = .022). On multivariate analysis, microsurgery was associated with lower risk (hazard ratio [HR] 0.09, 95% confidence interval [CI] 0.01-0.71) of, and LDLT had higher risk (HR 4.23, 95% CI 1.46-12.27) of arterial complications. Biliary complications were associated with LDLT (HR 3.91, 95% CI 1.30-11.71) and dual biliary anastomoses (HR 5.26, 95% CI 1.15-24.08) but not with occurrence of HA complications. Worse patient survival was associated with the occurrence of any HA complication (HR 4.11, 95% CI 1.78-9.48). Hepatic arterial complications can be reduced using microsurgical techniques for the anastomosis, resulting in improved patient survival outcomes after liver transplantation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

BACKGROUND In solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, coronavirus disease 2019 (COVID-19) can contribute to a severe clinical course and an increased risk of death. Thus, patients awaiting a SOT or HSCT face the dilemma of choosing between a life-saving treatment that presents a significant threat of COVID-19 and the risk of waitlist dropout, progression of disease, or mortality. The lack of established literature on COVID-19 complicates the issue as patients, particularly those with inadequate health literacy, may not have the resources needed to navigate these decisions. MATERIAL AND METHODS We conducted a standardized phone survey of patients awaiting SOT or HSCT to assess the prevalence of inadequate health literacy and attitudes toward transplant during the COVID-19 pandemic. RESULTS Seventy-one patients completed the survey, with a response rate of 84.5%. Regardless of health literacy, most waitlisted candidates recognized that the current pandemic is a serious situation affecting their care and that COVID-19 poses a significant risk to their health. Despite the increased risks, most patients reported they would choose immediate transplantation if there was no foreseeable end to the pandemic, and especially if the medical urgency did not permit further delay. There were no differences in responses across the patient waitlist groups for heart, kidney, liver, and stem cell transplant. CONCLUSIONS These findings can help transplant centers decide how transplantation services should proceed during this pandemic and can be used to educate patients and guide discussions about informed consent for transplant during the COVID-19 pandemic.

Background: Venous reconstruction has been recently demonstrated to be safe for tumours with invasion into portal vein and/or superior mesenteric vein. This study aims to compare the patency between various venous reconstructions., Methods: This is retrospective study of 76 patients who underwent pancreaticoduodenectomy or total pancreatectomy with venous reconstruction from 2006 to 2018. Patient demographics, tumour histopathology, morbidity, mortality and patency were studied. Kaplan-Meier estimates were performed for primary venous patency., Results: Sixty-two patients underwent pancreaticoduodenectomy and 14 underwent total pancreatectomy. Forty-seven, 19 and 10 patients underwent primary repair, end-to-end anastomosis and interposition graft respectively. Major morbidity (Clavien-Dindo >grade 2) and 30-day mortality were 14/76(18.4%) and 1/76(1.3%) respectively. There were 12(15.8%) venous occlusion including 4(5.3%) acute occlusions. Overall 6-month, 1-year and 2-year primary patency was 89.1%, 92.5% and 92.3% respectively. 1-year primary patency of primary repair was superior to end-to-end anastomosis and interposition graft (primary repair 100%, end-to-end anastomosis 81.8%, interposition graft 66.7%, p = 0.045). Pairwise comparison also demonstrated superior 1-year patency of primary repair (adjusted p = 0.037). There was no significant difference between the cumulative venous patency for each venous reconstruction method: primary repair 84±6%, end-to-end anastomosis 75±11% and interposition graft 76±15% (p = 0.561)., Conclusion: 1-year primary venous patency of primary repair is superior to end-to-end anastomosis and interposition graft., Competing Interests: The authors have declared that no competing interests exist.

We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The current coronavirus disease 2019 (COVID-19) pandemic has not only caused global social disruptions but has also put tremendous strain on healthcare systems worldwide. With all attention and significant effort diverted to containing and managing the COVID-19 outbreak (and understandably so), essential medical services such as transplant services are likely to be affected. Closure of transplant programs in an outbreak caused by a highly transmissible novel pathogen may be inevitable owing to patient safety. Yet program closure is not without harm; patients on the transplant waitlist may die before the program reopens. By adopting a tiered approach based on outbreak disease alert levels, and having hospital guidelines based on the best available evidence, life-saving transplants can still be safely performed. We performed a lung transplant and a liver transplant successfully during the COVID-19 era. We present our guidelines and experience on managing the transplant service as well as the selection and management of donors and recipients. We also discuss clinical dilemmas in the management COVID-19 in the posttransplant recipient., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Hepatocellular carcinoma (HCC) is a common and deadly cancer with limited treatment options. Through genome-wide growth depletion screens using clustered regularly interspaced short palindromic repeats and expression profiling of primary HCC tumors, we identified 13 clinically relevant target genes with therapeutic potential. Subsequent functional annotation analysis revealed significant enrichment of these 13 genes in the cell cycle, cell death, and survival pathways. Non-structural maintenance of chromosomes condensin I complex subunit G (NCAPG) was ranked the highest among the depletion screens and multiple HCC expression datasets. Transient inhibition of NCAPG using specific small interfering RNAs resulted in a significant reduction in cell growth, migration, and the down-regulation of mitochondrial gene expression in vitro . Small homologous RNA-mediated knockdown of NCAPG significantly impaired cell viability, caused aberrant mitotic division, fragmented the mitochondrial network, and increased cell death in vitro . HCC cells with a reduced expression of NCAPG formed significantly smaller xenograft tumors in vivo . Importantly, high NCAPG expression was significantly associated with poorer overall and disease-free survival in HCC patients. High NCAPG expression is a novel prognostic biomarker to predict HCC early recurrence after surgical resection. In conclusion, NCAPG is an essential gene for HCC tumor cell survival. It represents a promising novel target for treating HCC and a prognostic biomarker for clinical management of HCC.-Wang, Y., Gao, B., Tan, P. Y., Handoko, Y. A., Sekar, K., Deivasigamani, A., Seshachalam, V. P., OuYang, H.-Y., Shi, M., Xie, C., Goh, B. K. P., Ooi, L. L., Hui, K. M. Genome-wide CRISPR knockout screens identify NCAPG as an essential oncogene for hepatocellular carcinoma tumor growth.

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., (© 2019 UICC.)

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., (© 2018 S. Karger AG, Basel.)

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., (© 2017 Royal Australasian College of Surgeons.)

Aim: To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas (HCC)., Methods: A systematic review of the published literature was performed using the PubMed database from 1 st January 1999 to 31 st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC. The primary end point was to determine the overall survival (OS) and disease free survival (DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve ( i.e ., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC (defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC., Results: We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to (1) BCLC stage B or C HCC, (2) Size of HCC and (3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7% (range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0% (range 0.0-42.0). The collective median 5-year OS of both stages was 27.9% (0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR (95%CI) = 1.00 (0.76-1.31)] and mortality [RR (95%CI) = 1.15 (0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%., Conclusion: Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to declare for any of the authors.

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., Competing Interests: There are no conflicts of interest

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.

Sorafenib is currently the only US Food and Drug Administration (FDA)-approved molecular inhibitor for the systemic therapy of advanced hepatocellular carcinoma (HCC). Aspirin has been studied extensively as an anti-inflammation, cancer preventive and therapeutic agent. However, the potential synergistic therapeutic effects of sorafenib and aspirin on advanced HCC treatment have not been well studied. Drug combination studies and their synergy quantification were performed using the combination index method of Chou-Talalay. The synergistic therapeutic effects of sorafenib and aspirin were evaluated using an orthotopic mouse model of HCC and comprehensive gene profiling analyses were conducted to identify key factors mediating the synergistic therapeutic effects of sorafenib and aspirin. Sorafenib was determined to act synergistically on HCC cells with aspirin in vitro . Using Hep3B and HuH7 HCC cells, it was demonstrated that sorafenib and aspirin acted synergistically to induce apoptosis. Mechanistic studies demonstrated that combining sorafenib and aspirin yielded significant synergistically anti-tumor effects by simultaneously silencing ACSL4 and the induction of GADD45B expression in HCC cells both in vitro and in the orthotopic HCC xenograft mouse model. Importantly, clinical evidence has independently corroborated that survival of HCC patients expressing ACSL4 high GADD45B low was significantly poorer compared to patients with ACSL4 low GADD45B high , thus demonstrating the potential clinical value of combining aspirin and sorafenib for HCC patients expressing ACSL4 high GADD45B low . In conclusion, sorafenib and aspirin provide synergistic therapeutic effects on HCC cells that are achieved through simultaneous silencing of ACSL4 and induction of GADD45B expression. Targeting HCC with ACSL4 high GADD45B low expression with aspirin and sorafenib could provide potential synergistic therapeutic benefits., Competing Interests: The authors declare no conflict of interest.

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., (© 2016 Royal Australasian College of Surgeons.)

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Many kinases have been found to be intimately involved in oncogenesis and the deregulation of kinase function has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. Previously, we have performed gene expression profile analysis on HCC samples and have identified a host of kinases that are remarkably overexpressed in HCC. Among these, the Maternal Embryonic Leucine Zipper Kinase (MELK) is highly overexpressed in HCC and its overexpression strongly correlates with early recurrence and poor patients' survival. Silencing MELK inhibited cell growth, invasion, stemness and tumorigenicity of HCC cells by inducing apoptosis and mitosis. We further showed that the overexpression of MELK in HCC samples strongly correlated with the cell cycle- and mitosis-related genes which are directly regulated as part of the forkhead transcription factor FoxM1-related cell division program. Together, our data establish MELK as an oncogenic kinase involved in the pathogenesis and recurrence of HCC and could provide a promising molecular target to develop therapeutic strategies for patients with advanced HCC., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

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.

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., (© 2015 Royal Australasian College of Surgeons.)

Objectives: Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. Alterations in microtubule-associated proteins (MAPs) have been observed in HCC. However, the mechanisms underlying these alterations remain poorly understood. Our aim was to study the roles of the MAP protein regulator of cytokinesis 1 (PRC1) in hepatocarcinogenesis and early HCC recurrence., Design: PRC1 expression in HCC samples was evaluated by microarray, immunoblotting and immunohistochemistry analysis. Molecular and cellular techniques including siRNA-mediated and lentiviral vector-mediated knockdown were used to elucidate the functions and mechanisms of PRC1., Results: PRC1 expression was associated with early HCC recurrence and poor patient outcome. In HCC, PRC1 exerted an oncogenic effect by promoting cancer proliferation, stemness, metastasis and tumourigenesis. We further demonstrated that the expression and distribution of PRC1 is dynamically regulated by Wnt3a signalling. PRC1 knockdown impaired transcription factor (TCF) transcriptional activity, decreased Wnt target expression and reduced nuclear β-catenin levels. Mechanistically, PRC1 interacts with the β-catenin destruction complex, regulates Wnt3a-induced membrane sequestration of this destruction complex, inhibits adenomatous polyposis coli (APC) stability and promotes β-catenin release from the APC complex. In vivo, high PRC1 expression correlated with nuclear β-catenin and Wnt target expression. PRC1 acted as a master regulator of a set of 48 previously identified Wnt-regulated recurrence-associated genes (WRRAGs) in HCC. Thus, PRC1 controlled the expression and function of WRRAGs such as FANCI, SPC25, KIF11 and KIF23 via Wnt signalling., Conclusions: We identified PRC1 as a novel Wnt target that functions in a positive feedback loop that reinforces Wnt signalling to promote early HCC recurrence., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Hypertrophy of the contralateral liver lobe after treatment with yttrium-90 ((90)Y) 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., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Purpose: Intra-arterial yttrium-90 ((90)Y) microsphere radioembolization (RE) is an emerging treatment option with good outcomes reported predominantly in hepatitis C Western populations with hepatocellular carcinoma (HCC). We report outcomes in predominantly hepatitis B Asian patients treated with (90)Y-RE focusing on overall survival (OS), time to progression (TTP), tumor response, pattern of tumor recurrence and adverse events. Prognostic factors for survival were also identified., Methods: A retrospective cohort study was conducted in a single tertiary institution. All non-trial patients treated with (90)Y-RE at our institution from 1 January 2008 to 30 June 2012 were included., Results: Data from 103 consecutive patients were analyzed. The majority of patients were Child-Pugh class A (59.2 %) and Barcelona Clinic Liver Cancer (BCLC) stage C (68.9 %). Median OS was 14.4 months (95 % CI 11.0-22.2), which varied by disease stage: Child-Pugh A, 21.7 months; Child-Pugh B, 7.1 months; BCLC B, 23.8 months; BCLC C, 11.8 months. Response and disease control rates by RECIST 1.1 were 21.2 and 59.6 %, respectively, while disease control for index lesions treated with (90)Y-RE was 100 %. Development of new intrahepatic lesions was the main reason for eventual disease progression. Median overall TTP was 5.3 months (95 % CI 4.1-10.0). Pretreatment vascular invasion, low serum albumin and elevated total bilirubin levels predicted poorer survival., Conclusions: Survival outcomes in hepatitis B Asian patients treated with (90)Y-RE for HCC are comparable to hepatitis C Western populations. While disease control for lesions treated with (90)Y-RE is excellent, the development of new lesions suggests a role for concomitant systemic therapy.

Background: Liposarcoma is the single most common soft tissue sarcoma in the retroperitoneum., Materials and Methods: A retrospective review of patients with primary retroperitoneal liposarcoma treated between June 1990 and June 2005 were conducted to evaluate the clinical results of resection for retroperitoneal liposarcomas (RPLS) and the prognostic factors for disease recurrence and patient survival in an Asian population., Results: Twenty-one patients operated on for curative intent (12 Males, 9 Females; mean age: 52.4 years) were evaluated. Of these, 13 presented with tumors that were well differentiated (61.9%), 4 (19.0%) with myxoid/round cell, 3 (14.3%) with dedifferentiated and 1(4.8%) with pleomorphic morphology. The median tumor burden was 36 cm (9-83). Median follow-up time was 62 months. There was no peri-operative mortality and morbidity occurred in 6(28.6%) patients. Surgical margins were involved in 10(47.6%) patients. Resection of contiguous organs was required in 15(71.4%) to achieve gross surgical margins. Eleven out of the 21(52%) of the patients had recurrence of the tumor. Median disease-free survival was 19 months and the overall 3- and 5-year survival rate was 87% and 49% respectively., Conclusion: An aggressive surgical approach in both primary and recurrent RPLS in our institution is associated with 3- and 5-year survival rate of 87% and 49% respectively. Contiguous organ resection is often required to achieve local control.

Pancreatic carcinoma has a poor prognosis and early detection is essential for potentially curative resection. Despite the wide array of diagnostic tools, preoperative detection of small pancreatic carcinomas remains difficult. We report a case of small pancreatic carcinoma of the head of pancreas with indeterminate findings on US, ERCP, MRI and EUS which was successfully diagnosed via fusion CT-PET. This case illustrates the utility of CT-PET in the diagnosis of patients with small pancreatic carcinoma with equivocal findings on conventional diagnostic modalities.