Optimal treatment strategies for gallbladder disease in pregnancy: a systematic review with dual network meta-analyses.

BACKGROUND: This study sought to determine the optimal treatment strategy and timing for cholecystectomy in managing gallbladder diseases during pregnancy. It evaluated the effectiveness of conservative management (CM), laparoscopic cholecystectomy (LC), and open cholecystectomy (OC) in pregnancy and compared cholecystectomy outcomes across three trimesters. METHODS: Studies comparing CM, LC, and OC or evaluating cholecystectomy outcomes across trimesters were included in a literature search until February 2024. Studies included were required to have at least 10 cases per treatment group and perform statistical comparisons. Two Bayesian network meta-analyses (NMAs) were conducted, and surface under cumulative ranking area (SUCRA) values, risk ratio (RR), mean difference (MD), and 95% credible intervals (CrIs) were calculated for outcomes of interest. RESULTS: Our study included 17 studies with 63,523 pregnant patients. The first NMA included data from 12 studies involving 29,052 pregnant women, revealing that LC had the lowest risk for preterm delivery, significantly lower than CM (RR: 0.23, 95% CrI: 0.07-0.55). LC also had a significantly reduced risk of fetal complications (RR: 0.42, 95% CrI: 0.16-0.57) and maternal complications (RR: 0.44, 95% CrI: 0.15-0.50) compared to OC. LC was associated with a significantly shorter length of stay than OC (MD: -2.77, 95% CrI: -8.37 to -2.87). The second NMA analyzed data from five population-based studies with 34,471 pregnant patients, finding no significant differences in preterm delivery and abortion rates across the three trimesters following cholecystectomy. Cholecystectomy performed in the third trimester significantly increased the risk of maternal complications, with relative risks compared to first (RR: 0.48, 95% CrI: 0.22-1.00) and second trimesters (RR: 0.42, 95% CrI: 0.21-0.93). CONCLUSIONS: LC is deemed the optimal treatment for gallbladder diseases during pregnancy. While cholecystectomy is safe to be performed across all trimesters, careful deliberation is recommended during the third trimester due to an increased risk of maternal complications.

ArtiSential® laparoscopic cholecystectomy versus single-fulcrum laparoscopic cholecystectomy: Which minimally invasive surgery is better?

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.

p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.

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.

Evaluation of the impact of prospective payment systems on cholecystectomy: A systematic review and meta-analysis.

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.

Comparative cost-effectiveness of open, laparoscopic, and robotic liver resection: A systematic review and network meta-analysis.

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.

Evaluation of the American College of Surgeons risk calculator in hepatectomy for metastatic colorectal cancer in a Southeast Asian population.

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.

Evaluating the economic efficiency of open, laparoscopic, and robotic distal pancreatectomy: an updated systematic review and network meta-analysis.

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.

Short-term outcomes of laparoscopic and robotic limited resections of pancreatic neuroendocrine tumours of the uncinate process: Report of six cases and review of the literature.

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.

The impact of hospital volume on liver resection: A systematic review and Bayesian network meta-analysis.

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.

Surveillance for Presumed BD-IPMN of the Pancreas: Stability, Size, and Age Identify Targets for Discontinuation.

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.

Histone-lysine N-methyltransferase EHMT2 (G9a) inhibition mitigates tumorigenicity in Myc-driven liver cancer.

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.

Limited liver resections in the posterosuperior segments: international multicentre propensity score-matched and coarsened exact-matched analysis comparing the laparoscopic and robotic approaches.

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.

Extending Surgical Resection for Hepatocellular Carcinoma Beyond Barcelona Clinic for Liver Cancer (BCLC) Stage A: A Novel Application of the Modified BCLC Staging System.

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.

Real-World Data on Clinical Outcomes of Patients with Liver Cancer: A Prospective Validation of the National Cancer Centre Singapore Consensus Guidelines for the Management of Hepatocellular Carcinoma.

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.

Resected pancreatic adenocarcinoma: An Asian institution's experience.

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.

Correlation of NUF2 Overexpression with Poorer Patient Survival in Multiple Cancers.

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.

Impact of Microsurgical Anastomosis of Hepatic Artery on Arterial Complications and Survival Outcomes After Liver Transplantation.

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.

Waitlisted Transplant Candidates' Attitudes and Concerns Toward Transplantation During COVID-19.

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.

Comparison between long and short-term venous patencies after pancreatoduodenectomy or total pancreatectomy with portal/superior mesenteric vein resection stratified by reconstruction type.

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.

Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma.

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.