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The Memorial Sloan Kettering Cancer Center nomogram, the predictive scoring system of Yamamoto et al, and the 3-point transfusion risk score of Lemke et al are models used to determine the probability of receiving intraoperative blood transfusion in patients undergoing liver resection. However, the external validity of these models remains unknown. The objective of this study was to evaluate their predictive performance in an external cohort of patients with hepatocellular carcinoma. We also aimed to identify predictors of blood transfusion and develop a new predictive model for blood transfusion.Post hoc analysis of our prospective database of 1,081 patients undergoing liver resection for hepatocellular carcinoma from 2001 to 2018. The predictive performance of current prediction models was evaluated using C statistics. Demographic and clinical variables as predictors of blood transfusion were assessed. Using logistic regression, an alternative model was created.The Lemke transfusion risk score performed better than the Memorial Sloan Kettering Cancer Center nomogram (0.69, 95% confidence interval 0.66-0.73 vs 0.66, 95% liver resection 0.62-0.69) (Plt; .001). The model from Yamamoto et al performed comparably with no statistically significant differences found through pairwise comparison. In our alternative model, hemoglobin level, albumin level, liver resection type, and tumor size were independent predictors of blood transfusion. The new HATS model obtained a C statistic of 0.74 (95% confidence interval 0.71-0.78), performing significantly better than the previous 3 models (P ≤ 0.001 for all).The existing Memorial Sloan Kettering Cancer Center, Yamamoto et al, and Lemke et al had nomograms with the suboptimal accuracy of predicting risk of intraoperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma. The proposed HATS model was more accurate at predicting patients at risk of blood transfusion.

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.

While minimally invasive liver resections (MILR) have demonstrated advantages in improved post-operative recovery, widespread adoption is hampered by inherent technical difficulties. Our study attempts to analyze the role of anthropometric measures in MILR-related outcomes.Between 2012 and 2020, 676 consecutive patients underwent MILR at the Singapore General Hospital of which 565 met study criteria and were included. Patients were stratified based on Body Mass Index (BMI) as well as Standardized Liver Volumes (SLV). Associations between BMI and SLV to selected peri-operative outcomes were analyzed using restricted cubic splines.A BMI of ≥ 29 was associated with increase in blood loss [Mean difference (MD) 69 mls, 95% CI 2 to 137] as well as operative conversions [Relative Risk (RR) 1.63, 95% CI 1.02 to 2.62] among patients undergoing MILR while a SLV of 1600 cc or higher was associated with an increase in blood loss (MD 30 mls, 95% CI 10 to 49). In addition, a BMI of ≤ 20 was associated with an increased risk of major complications (RR 2.25, 95% 1.16 to 4.35). The magnitude of differences observed in these findings increased with each unit change in BMI and SLV.Both BMI and SLV were useful anthropometric measures in predicting peri-operative outcomes in MILR and may be considered for incorporation in future difficulty scoring systems for MILR.

A systematic review and network meta-analysis was performed to compare outcomes after living donor right hepatectomy via the following techniques: conventional open (Open), mini-laparotomy (Minilap), hybrid (Hybrid), totally laparoscopic (Lap), and robotic living donor right hepatectomy (Robotic).PubMed, EMBASE, Cochrane, and Scopus were searched from inception to August 2021 for comparative studies of patients who underwent living donor right hepatectomy.Nineteen studies comprising 2,261 patients were included. Operation time was longer in Lap versus Minilap and Open (mean difference 65.09 min, 95% confidence interval 3.40-126.78 and mean difference 34.81 minutes, 95% confidence interval 1.84-67.78), and in Robotic versus Hybrid, Lap, Minilap, and Open (mean difference 144.72 minutes, 95% confidence interval 89.84-199.59, mean difference 113.24 minutes, 95% confidence interval 53.28-173.20, mean difference 178.33 minutes, 95% confidence interval 105.58-251.08 and mean difference 148.05 minutes, 95% confidence interval 97.35-198.74, respectively). Minilap and Open were associated with higher blood loss compared to Lap (mean difference 258.67 mL, 95% confidence interval 107.00-410.33 and mean difference 314.11 mL, 95% confidence interval 143.84-484.37) and Robotic (mean difference 205.60 mL, 95% confidence interval 45.92-365.28 and mean difference 261.04 mL, 95% confidence interval 84.26-437.82). Open was associated with more overall complications compared to Minilap (odds ratio 2.60, 95% confidence interval 1.11-6.08). Recipient biliary complication rate was higher in Minilap and Open versus Hybrid (odds ratio 3.91, 95% confidence interval 1.13-13.55 and odds ratio 11.42, 95% confidence interval 2.27-57.49), and lower in Open versus Minilap (OR 0.07, 95% confidence interval 0.01-0.34).Minimally invasive donor right hepatectomy via the various techniques is safe and feasible when performed in high-volume centers, with no major differences in donor complication rates and comparable recipient outcomes once surgeons have mounted the learning curve.

Background Presently, data on the impact of enhanced recovery protocols on the outcomes of laparoscopic liver resection remain limited. We performed propensity matched analysis comparing the outcomes between patients undergoing laparoscopic liver resection before and after the introduction of an enhanced recovery protocol. Methods Between 2013 and 2019, 462 consecutive patients underwent laparoscopic liver resection by 3 surgeons of which 360 met the study inclusion criteria. There were 89 patients who underwent surgery under an enhanced recovery protocol and 271 without an enhanced recovery protocol. One-to-one propensity matched analysis was performed for 84 enhanced recovery protocol patients and 84 nonenhanced recovery protocol patients. Results Comparisons between propensity matched cohorts revealed that patients who received laparoscopic liver resection with enhanced recovery protocol had reduced median blood loss (200 vs 300 mL, P = .013), postoperative stay (3 vs 4 days, P = .003), and lower open conversion rates (0% vs 8.3%, P = .008). There was no difference in other key perioperative outcomes such as operation time, postoperative morbidity, postoperative major morbidity, and 30-day readmission rates. Conclusion A combined approach of enhanced recovery protocol and laparoscopic liver resection was associated with improved perioperative outcomes as opposed to laparoscopic liver resection alone.

The majority of evidence with regards to minimally invasive liver resection (MILR) favors its application in minor hepatectomies. We conducted a propensity score-matched (PSM) analysis to determine its feasibility and safety in major hepatectomies (MIMH) for liver malignancies.Retrospective review of 130 patients who underwent MIMH and 490 patients who underwent open major hepatectomy (OMH) for malignant pathologies was performed. PSM in a 1:1 ratio identified two groups of patients with similar baseline clinicopathological characteristics. Perioperative outcomes were then compared. Major hepatectomies included traditional major (3 segments) and technical major hepatectomies (right anterior and right posterior sectionectomies).Both cohorts were well-matched for baseline characteristics after PSM. Of 130 MIMH cases, there were 12 conversions to open. Comparison of perioperative outcomes demonstrated a significant association of MIMH with longer operation time and more frequent application of Pringle's maneuver (PM), but decreased postoperative stay. These results were consistent on a subgroup analysis that only included patients undergoing traditional major hepatectomies. A second subgroup analysis restricted to cirrhotic patients demonstrated that while perioperative outcomes were equivalent, MIMH was similarly associated with a longer operative time. Subset analyses of resections performed after 2015 demonstrated that MIMH was additionally associated with a lower postoperative morbidity compared to OMH.Comparison of perioperative and short-term oncological outcomes between MIMH and OMH for malignancies demonstrated that MIMH is feasible and safe. It is associated with a shorter hospital stay at the expense of a longer operation time compared to OMH.

Introduction We performed this study in order to investigate the impact of tumour size on the difficulty of MILR, as well as to elucidate the optimal tumour size cut-off/s to distinguish between ‘easy’ and ‘difficult’ MILRs. Materials and methods This is retrospective review of 603 consecutive patients who underwent MILR between 2006 and 2019 of which 461 met the study inclusion criteria. We first conducted an exploratory analysis to visualize the associations between tumor size and various surrogates of laparoscopic difficulty in order to determine to optimal tumor size cutoff for stratification. Visual inspection of flexible spline-based models as well as quantitative evidence determined that perioperative outcomes differed between patients with tumor size of 30–69 mm and tumours ≥70 mm. These cutoffs were used for further downstream analyses. Results The cohort of 461 patients was divided into 3 groups based on tumour diameter size. Patients with larger tumours experienced longer operating times ((PGroup 2 vs 1 Conclusion Although tumour size of 30 mm serves as an optimal cut-off for predicting difficult resections as per the Iwate criteria, a trichotomy (

Summary Background Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma. Methods Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov , NCT03033446 and has been completed. Findings 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4–48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3–4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites). Interpretation Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread. Funding National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex.

Minimally invasive distal pancreatectomy (MIDP) is being adopted increasingly worldwide. This study aimed to compare the short-term outcomes of patients who underwent MIDP versus open distal pancreatectomy (ODP). A retrospective review of all patients who underwent a DP in our institution between 2005 and 2019 was performed. Propensity score matching based on relevant baseline factors was used to match patients in the ODP and MIDP groups in a 1:1 manner. Outcomes reported include operative duration, blood loss, postoperative length of stay, morbidity, mortality, postoperative pancreatic fistula rates, reoperation and readmission. In total, 444 patients were included in this study. Of 122 MIDP patients, 112 (91.8%) could be matched. After matching, the median operating time for MIDP was significantly longer than ODP [260 min (200–346.3) vs 180 (135–232.5), p

We read with great interest the article published by Zuo et al , which highlighted the presence of SARS-CoV-2 RNA in stool samples during active and convalescence phases of COVID-19 infection.1 However, no study has reported the presence of viral antigens within GI and hepatic organs during the convalescent phase. Using conventional immunohistochemistry, we detected SARS-CoV-2 nucleocapsid protein (NP) in the colon, appendix, ileum, haemorrhoid, liver, gallbladder and lymph nodes (figure 1A–K) from five patients who recovered from COVID-19, ranging from 9 to 180 days after testing negative for SARS-CoV-2 (online supplemental table 1). Notably, when multiple tissues were obtained from one patient (patients 1 and 4), all the tissues showed the presence of the viral antigen, suggesting widespread multiorgan involvement of the viral infection. Interestingly, for the colon, the viral antigen was only present in normal colonic crypts and polyps but not in the neoplastic tissues (figure 1Q). Similar negative staining in the hepatocellular carcinoma tumour region was also observed (figure 1R) albeit the positive staining in some of the scattered immune cells (figure 1D). Validating our findings, we detected SARS-CoV-2 spike protein (figure 1L–P) and RNA (figure 2B–F) in the above-mentioned tissues using conventional immunohistochemistry and RNAscope, respectively. However, we were unable to detect viral RNA in some patients’ tissues (online supplemental table 1), possibly because of higher RNA degradation rate as compared with protein and other patient-dependent factors such as disease severity, time since recovery and basal metabolic rate.### Supplementary data [gutjnl-2021-324280supp001.pdf] Figure 1 Immunohistochemical staining of the SARS-CoV-2 nucleocapsid and spike proteins in intestinal and hepatic tissues. (A and B) Positive SARS-CoV-2 nucleocapsid protein (NP) staining in colonic crypts (A) and appendix (B), both with a granular supranuclear cytoplasmic pattern. (C) positive SARS-CoV-2 NP staining in scattered immune cells …

BACKGROUND This study aims to compare the short- and long-term outcomes of patients undergoing minimally invasive liver resection (MILR) versus open liver resection (OLR) for nonrecurrent hepatocellular carcinoma (HCC). METHODS Review of 204 MILR and 755 OLR without previous LR performed between 2005 and 2018. 1:1 coarsened exact matching (CEM) and 1:1 propensity-score matching (PSM) were performed. RESULTS Overall, 190 MILR were well-matched with 190 OLR by PSM and 86 MILR with 86 OLR by CEM according to patient baseline characteristics. After PSM and CEM, MILR was associated with a significantly longer operation time [230 min (interquartile range [IQR], 145-330) vs. 160 min (IQR, 125-210), p

Our primary objective was to determine if receiving intraoperative blood transfusion was a significant prognostic factor for overall and recurrence-free survival after curative resection of hepatic cellular carcinoma (HCC).Between 2001 and 2018, 1092 patients with histologically proven primary HCC who underwent curative liver resection were retrospectively reviewed. Primary study endpoints were recurrence-free survival (RFS) and overall survival (OS). The main analysis was undertaken using propensity-score matching (PSM) to minimize confounding and selection biases in the comparison of patients with or without transfusion.There were 220 patients who received and 666 patients who did not receive intraoperative blood transfusion. The PSM cohort consisted of 163 pairs of patients. After PSM, the only perioperative outcome that appeared to significantly affect whether patients would receive blood transfusion was median blood loss (p = 0.001). In the PSM cohort, whether patients received blood transfusion was neither associated with OS (p = 0.759) nor RFS (p = 0.830). When the volume of blood transfusion was analyzed as a continuous variable, no significant dose-response relationship between blood transfusion volume and HR for OS and RFS was noted.Intraoperative blood transfusion had no significant impact on the survival outcomes in patients who receive curative resection in primary HCC.

Ian JY Wee,1 Fiona NN Moe,1 Rehena Sultana,2 Reiko WT Ang,1 Pearly PS Quek,3 Brian Kim Poh Goh,1 Chung Yip Chan,1 Peng Chung Cheow,1 Alexander YF Chung,1 Prema Raj Jeyaraj,1 Ye Xin Koh,1 Peter OP Mack,1 London Lucien PJ Ooi,1 Ek Khoon Tan,1 Jin Yao Teo,1 Juinn Huar Kam,1 Jacelyn SS Chua,1 Ashley WY Ng,1 Jade SQ Goh,1 Pierce KH Chow1,4 1Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore; 2Center of Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore; 3Ministry of Health Holdings, Singapore, Singapore; 4Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, SingaporeCorrespondence: Pierce KH Chow, Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore, Tel +65 6576 2151, Email pierce.chow@duke-nus.edu.sgObjective: 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.Keywords: hepatocellular carcinoma, surgical resection, Barcelona clinic liver cancer

IL-17-producing CD8 (Tc17) T cells have been shown to play an important role in infection and chronic inflammation, however their implications in hepatocellular carcinoma (HCC) remain elusive. In this study, we performed cytometry by time-of-flight (CyTOF) and revealed the distinctive immunological phenotypes of two IFNγ

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with high rates of recurrence post-resection. Repeat hepatectomy (RH) and radiofrequency ablation (RFA) are the mainstays for managing recurrent HCC following initial curative resection. This retrospective study aims to determine the average treatment effect of RH and RFA in patients with recurrent HCC. From 2000 to 2016, a total of 219 consecutive patients with recurrent HCC who underwent either RH or RFA were included in the study. The analysis was performed using inverse probability of treatment weighting (IPTW), and propensity score-matched (PSM) methods. The minor and major post-operative morbidity after propensity score-matched analysis for the RH group was 30.0% and 6.0%, respectively, and 19.2% and 0.0% (p = 0.1006), respectively, for the RFA group. After propensity score matching, the median OS for RH and RFA was 85.5 (IQR, 33.5–not reached) and 53.3 months (IQR, 27.5–not reached) (p = 0.8474), respectively. There was no significant difference in 90-day mortality between both groups (p = 0.1287). RH showed improved long-term overall survival over RFA at the third [71.3% versus 65.7% (p = 0.0432)], fifth [59.9% versus 45.4% (p = 0.0271)] and tenth [35.4% versus 32.2% (p = 0.0132)] year follow-up, respectively. Median time to recurrence was 11.1 (IQR, 5.0–33.2) and 28.0 months (IQR, 9.1–not reached) (p = 0.0225) for the RFA and RH group, respectively. RH confers a late survival benefit compared with RFA for patients with recurrent HCC despite a higher morbidity rate.

Background Various difficulty scoring systems (DSS) have been formulated to grade the complexity of laparoscopic hepatectomies (LH). This study aims to externally validate and compare 4 contemporary DSS including the Iwate, Institut Mutualiste Montsouris (IMM), Southampton and Hasegawa DSS in predicting the intraoperative technical difficulty and postoperative outcomes after LH. Methods Retrospective review of 548 consecutive patients who underwent LH of which 455 met the study inclusion criteria. Outcomes measures of technical difficulty included operation time, Pringles maneuver, blood loss and blood transfusion rate. Postoperative outcomes measured included morbidity, major morbidity and postoperative hospital stay. Results There was a statistically significant progressive increase in blood loss, blood transfusion rate, operation time and postoperative stay associated with all 4 DSS. There was also good calibration with respect to blood loss, operation time, Pringles maneuver, open conversion rate, postoperative morbidity, postoperative major morbidity and postoperative stay for all 4 DSS. The Southampton score demonstrated the poorest calibration in terms of operation time and discrimination in terms of application of Pringles maneuver and major morbidity amongst all 4 systems. Conclusion All 4 DSS significantly correlated with outcome measures associated with intraoperative technical difficulty and postoperative outcomes. The Southampton DSS was the poorest system in our cohort of patients.

INTRODUCTION Fluorescence imaging (FI) with indocyanine green (ICG) is increasingly implemented as an intraoperative navigation tool in hepatobiliary surgery to identify hepatic tumours. This is useful in minimally invasive hepatectomy, where gross inspection and palpation are limited. This study aimed to evaluate the feasibility, safety and optimal timing of using ICG for tumour localisation in patients undergoing hepatic resection. METHODS From 2015 to 2018, a prospective multicentre study was conducted to evaluate feasibility and safety of ICG in tumour localisation following preoperative administration of ICG either on Day 0–3 or Day 4–7. RESULTS Among 32 patients, a total of 46 lesions were resected: 23 were hepatocellular carcinomas (HCCs), 12 were colorectal liver metastases (CRLM) and 11 were benign lesions. ICG FI identified 38 (82.6%) lesions prior to resection. The majority of HCCs were homogeneous fluorescing lesions (56.6%), while CLRM were homogeneous (41.7%) or rim-enhancing (33.3%). The majority (75.0%) of the lesions not detected by ICG FI were in cirrhotic livers. Most (84.1%) of ICG-positive lesions detected were < 1 cm deep, and half of the lesions ≥ 1 cm in depth were not detected. In cirrhotic patients with malignant lesions, those given ICG on preoperative Day 0−3 and Day 4−7 had detection rates of 66.7% and 91.7%, respectively. There were no adverse events. CONCLUSION ICG FI is a safe and feasible method to assist tumour localisation in liver surgery. Different tumours appear to display characteristic fluorescent patterns. There may be no disadvantage of administering ICG closer to the operative date if it is more convenient, except in patients with liver cirrhosis.

The presence of previous abdominal surgery (PAS) has traditionally been considered to add difficulty to and increase risk of complications of laparoscopic procedures. This study aims to analyse the impact of non-liver-related PAS on the difficulty of minimally invasive liver resections (MILRs). After exclusion of patients with concomitant major surgical procedures as well as previous liver resections, 515 consecutive patients undergoing MILR in Singapore General Hospital from 2006 to 2019 were analysed, consisting of 161 MILR in patients with previous abdominal surgery (WPAS) and 354 MILR in patients without previous abdominal surgery (WOPAS). Propensity score-matched (PSM) comparison was performed between WPAS and WOPAS groups. In addition, subgroup analysis was made comparing previous upper or lower abdominal surgery and open versus minimally invasive approach of PAS. Outcomes measured include those associated with operative difficulty such as open conversion rates, operative time, blood loss, as well as morbidity and mortality rates. MILR outcomes in patients WPAS are not inferior to those WOPAS. Overall open conversion rate was 8.2%, higher in patients WOPAS compared to patients WPAS (11.9% versus 3.5%, p = 0.015). Operating time (p = 0.942), blood loss (p = 0.063), intraoperative blood transfusion (p = 0.750), length of hospital stay (p = 0.206), morbidity (p = 0.217) and 30- and 90-day mortality (p = 1 & p = 0.367) were comparable between the two groups and subgroup analysis. Outcomes of MILR in patients with previous non-liver-related abdominal surgery are not inferior to patients without previous abdominal surgery.

The management of post-liver resection recurrence is often the life-limiting factor in HCC treatment. While much has been published on intrahepatic recurrence and lung metastasis, there is a relative lack of data on intraabdominal extrahepatic metastasis (EHM). We sought to evaluate the outcomes of patients post-resection of intraabdominal EHM and assess preoperative factors predictive of early recurrence post-metastasectomy. We performed a retrospective review of 25 consecutive patients who underwent metastasectomy for intraabdominal EHM from 2003 to 2016 at our institution. Of the 25 cases of EHM, 16 were in the peritoneum, 3 in the adrenal glands, 3 in the large bowel, 1 in the spleen, 1 in the pancreas and 1 in the omentum. Median overall survival was 27 months (IQR 15–89 months). Twenty-one patients (84%) developed recurrence post-metastasectomy of EHM of which 12 patients experienced early recurrence within 12 months. The median time to recurrence post-metastasectomy was 11(IQR 15.5) months. Multivariate analysis demonstrated both hepatitis B (11 (91.6%) versus 4 (44.4%), p = 0.00) status and high tumour grade (8 (66.6%) versus 3 (25%), p = 0.004) to be significant independent predictors of early recurrence. Patients who experienced early recurrence had a significantly shorter median overall survival (18 months (95% CI 12.9–23.0)) compared to those who did not (89 months (95% CI 24.8–153.1), p = 0.004). Patients with EHM who underwent metastasectomy had a median overall survival of 27 months. Hepatitis B positivity and high primary tumour grade were preoperative predictors of futile surgery. All 7 patients who had both hepatitis B and high tumour grade experienced early recurrence post-metastasectomy.

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.

Although numerous long non-coding RNAs (lncRNAs) were reported to be deregulated in Hepatocellular Carcinoma (HCC), experimentally characterized, and/or associated with patient's clinical characteristics, there is, thus far, minimal concerted research strategy to identify deregulated lncRNAs that modulate prognosis of HCC patients. Here, we present a novel strategy where we identify lncRNAs, which are not only de-regulated in HCC patients, but are also associated with pertinent clinical characteristics, potentially contributing to the prognosis of HCC patients. LOC101926913 (LOC) was further characterized because it is the most highly differentially expressed amongst those that are associated with the most number of clinical features (tumor-stage, vascular and tumor invasion and poorer overall survival). Experimental gain- and loss-of-function manipulation of LOC in liver cell-lines highlight LOC as a potential onco-lncRNA promoting cell proliferation, anchorage independent growth and invasion. LOC expression in cells up-regulated genes involved in GTPase-activities and downregulated genes associated with cellular detoxification, oxygen- and drug-transport. Hence, LOC may represent a novel therapeutic target, modulating prognosis of HCC patients through up-regulating GTPase-activities and down-regulating detoxification, oxygen- and drug-transport. This strategy may thus be useful for the identification of clinically relevant lncRNAs as potential biomarkers/targets that modulate prognosis in other cancers as well.

Introduction The impact on clinical practice of the international guidelines including the Sendai Guidelines (SG06) and Fukuoka Guidelines (FG12) on the management of cystic lesions of the pancreas (CLP) has not been well-studied. The primary aim was to examine the changing trends and outcomes in the surgical management of CLP in our institution over time and to determine the impact of these guidelines on our institution practice. Methods 462 patients with surgically-treated CLP were retrospectively reviewed and classified under the 2 guidelines. The cohort was divided into 3 time periods: 1998–2006, 2007–2012 and 2013 to 2018. Results Comparison across the 3 time periods demonstrated significantly increasing frequency of older patients, asymptomatic CLP, male gender, smaller tumor size, elevated Ca 19-9, use of magnetic resonance imaging (MRI) and use of endoscopic ultrasound (EUS) prior to surgery. There was also significantly increasing frequency of adherence to the international guidelines as evidenced by the increasing proportion of HRSG06 and HRFG12 CLP with a corresponding lower proportion of LRSG06 and LRFG12 being resected. This resulted in a significantly higher proportion of resected CLP whereby the final pathology confirmed that a surgery was actually indicated. Conclusions Over time, there was increasing adherence to the international guidelines for the selection of patients for surgical resection as evidenced by the significantly increasing proportion of HRSG06 and HRFG06 CLPs undergoing surgery. This was associated with a significantly higher proportion of patients with a definitive indication for surgery. These suggested that over time, there was a continuous improvement in our selection of appropriate CLP for surgical treatment.

Despite the wide use of laparoscopy for liver resection, laparoscopic caudate lobe resections(L-CLR) remain technically challenging, only attempted by experts in the field. The primary objective of this study was to determine the safety and compare the perioperative outcomes of L-CLR with O-CLR based on our single institution experience in a 1:2 propensity score-matched controlled study based on our single institution experience.Between 2004 and 2020, 67 consecutive patients who underwent CLR at Singapore General Hospital were identified. Propensity score matching (PSM) of laparoscopic versus open caudate lobe resections(O-CLR) was performed in a 1:2 ratio with no replacements using nearest neighbour matching method.L-CLR was associated with a significantly decreased median blood loss (150 mL versus 500 mL, P = 0.001) and a decreased median post-operative stay (3 days versus 7.5 days, P = 0.01) in the unmatched cohorts. After 1:2 propensity score matching, these results were again demonstrated with a significantly lower blood loss (150 mL versus 400 mL, P = 0.016) and a shorter postoperative stay (3 days versus 7 days, P = 0.01) in favour of L-CLR. 30-day readmission and major morbidity (Clavien-Dindo grade 2) rates were all in favour of L-CLR as well but could not reach statistical significance.L-CLR can be safely performed by experienced surgeons. It is associated with decreased blood loss and shorter perioperative stay compared to O-CLR.

Introduction Over the years, several guidelines have been introduced to guide management of mucinous pancreatic cystic neoplasms (mPCN). In this study, we aimed to evaluate and compare the clinically utility of the Sendai-06, Fukuoka-12, Fukuoka-17 and European-18 guidelines in predicting malignancy of mPCN. Methods One hundred and eighty-eight patients with mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasm (IPMN) who underwent surgery were retrospectively reviewed and classified under the 4 guidelines. Malignancy was defined as high grade dysplasia and invasive carcinoma. Results Raised CA19-9>37U/ml, enhancing mural nodule≥5 mm and main pancreatic duct≥10 mm were significantly associated with malignancy on multivariate analysis. Increasing number of high risk features, absolute indications (European-18), worrisome risk or relative indications (European-18) were significantly associated with an increased likelihood of malignancy. The positive predictive values (PPV) of high risk features for Sendai-06, Fukuoka-12, Fukuoka-17 and absolute indications (European-18) for malignancy were 53%, 76%, 78% and 78% respectively. The negative predictive values (NPV) of the Sendai-06, Fukuoka-12 and Fukuoka-17 were 100%, while that of the European-18 was 92%. Risk of malignancy for patients with ≥4 worrisome features (Fukuoka-17) and ≥3 relative indications (European-18) was 66.7% and 75.0% respectively. Conclusions All 4 guidelines studied were useful in the initial triage of mPCN for the risk stratification of malignancy. The Fukuoka-17 had the highest PPV and NPV.

BACKGROUND At present, the majority of outcome studies of survival of hepatocellular carcinoma (HCC) post-liver resection (post-LR) present actuarial survival data, which often results in overestimation of survival. We sought to evaluate the actual 10-year survival post-LR for HCC and identify variables that are associated with long-term survival. METHODS We performed a retrospective review of 600 consecutive patients who underwent primary LR for HCC from 2000 to 2010 at our institution. Twenty-eight patients (4.7%) with 90-day mortality and 125 patients who were lost to follow-up within 10 years were excluded leaving 447 patients who met the study criteria. RESULTS There were 140 actual 10-year survivors of which 57 (40.7%) had a recurrence within 10 years. The actual 10-year overall survival (OS) rate of the 447 patients was 31.5% and the actual 10-year recurrence-free survival (RFS) was 18.6%. Multivariate analyses demonstrated that only age >65 years (OR, 0.29; p

The impact of liver cirrhosis on the difficulty of minimal invasive liver resection (MILR) remains controversial and current difficulty scoring systems do not take in to account the presence of cirrhosis as a significant factor in determining the difficulty of MILR. We hypothesized that the difficulty of MILR is affected by the presence of cirrhosis. Hence, we performed a 1:1 matched-controlled study comparing the outcomes between patients undergoing MILR with and without cirrhosis including the Iwate system and Institut Mutualiste Montsouris (IMM) system in the matching process. Between 2006 and 2019, 598 consecutive patients underwent MILR of which 536 met the study inclusion criteria. There were 148 patients with cirrhosis and 388 non-cirrhotics. One-to-one coarsened exact matching identified approximately exact matches between 100 cirrhotic patients and 100 non-cirrhotic patients. Comparison between MILR patients with cirrhosis and non-cirrhosis in the entire cohort demonstrated that patients with cirrhosis were associated with a significantly increased open conversion rate, transfusion rate, need for Pringles maneuver, postoperative, stay, postoperative morbidity and postoperative 90-day mortality. After 1:1 coarsened exact matching, MILR with cirrhosis were significantly associated with an increased open conversion rate (15% vs 6%, p = 0.03), operation time (261 vs 238 min, p

Objective Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC). Methods This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients. Results 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5–419.5 versus 172.5 IU/L IQR 115–298 respectively, p = 0.61). Groups were similar in secondary endpoints. Conclusion This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy.

Background Resection of colorectal liver metastases (CLM) has been established as the standard of care. This study aims to compare the change in clinicopathological characteristics of patients who underwent curative resection of CLM across two time periods—2000 to 2010 (P1) and 2011 to 2016 (P2) and evaluate the prognostic impact of these characteristics on survival outcomes. Methods Patients who undergo liver resection for CLM at Singapore General Hospital from January 2000 to December 2016 were identified from a prospectively maintained database. The primary end point was overall survival. Results There were 183/318 (57.5%) patients and 135/318 (42.5%) patients in P1 and P2, respectively. There was a lower proportion of patients who had nodal metastases from primary colorectal cancer and clinical risk score (CRS) less than 3 in P2 when compared to P1. There was no difference in survival between both time periods. Independent predictors of survival for the cohort were CEA levels ≥ 200 ng/ml, primary tumour grade and lymph nodal status. Independent predictors of poor survival in P1 were poorly differentiated colorectal cancer and nodal metastases while in P2, independent predictors of poor survival were multiple liver metastases and nodal metastases. Conclusion Nodal metastases from primary colorectal cancer are an independent predictor of poor survival across time for resectable CLM. Although there is no difference in survival between the two time periods, patients with multiple liver metastases should be carefully considered prior to surgery as it is also an independent predictor of overall survival.

Although hepatectomy is the mainstay of curative therapy for hepatocellular carcinoma (HCC), post-operative complications remain high. Presently there is conflicting data on the impact of morbidity on oncologic outcomes. We sought to identify predictors for the occurrence of post-hepatectomy complications, as well as to analyse the impact on overall survival (OS) and recurrence-free survival (RFS).We performed a retrospective review of 888 patients who underwent resection for HCC from 2001 to 2016 in our institution.A total of 237 patients (26.7%) developed 254 complications of Clavien-Dindo Grade ≥2. Hepatitis B (p = 0.0397), elevated ASA score (p = 0.0002), higher platelet counts (p = 0.0277), raised pre-operative APRI scores (p = 0.0105) and bloodloss (p 0.0001) were independently associated with the development of complications. After propensity-score matching, 458 patients were compared in a 1:1 ratio (229 with complications versus 229 without). Patients with complications had significantly longer median length of stay (9 days [IQR 7-15] versus 6 days [IQR 5-8], p 0.0001), higher 90-day mortality rates as well as inferior OS (p = 0.0139), but there was no difference in RFS (p = 0.4577). Age (p = 0.0006), elevated Child Pugh points (p 0.0001), microvascular invasion (p = 0.0002), multifocal tumours (p = 0.0002), R1 resection (p = 0.0443) and development of complications (p = 0.0091) were independent predictors of inferior OS.Post-operative morbidity affected both short-term and OS outcomes after hepatectomy for HCC. Hepatitis B, higher ASA scores, elevated preoperative APRI and increased blood loss were found to predict a higher likelihood of developing complications. This may potentially be mitigated by careful patient selection and adopting strict measures to minimise intraoperative bleeding.

Backgrounds/aims This study aims to describe our experience with minimally-invasive distal pancreatectomies, with emphasis on the comparison between robotic distal pancreatectomy (RDP) and laparoscopic distal pancreatectomy (LDP). Methods Retrospective review of 102 consecutive RDP and LDP from 2006 to 2019 was performed. Results There were 27 and 75 patients who underwent RDP and LDP, respectively. There were 12 (11.8%) open conversions and 16 (15.7%) patients had major (＞grade 2) morbidities. Patients who underwent RDP had significantly higher rates of splenic preservation (44.4% vs. 13.3%, p=0.002), higher rates of splenic-vessel preservation (40.7% vs. 9.3%, p=0.001), higher median difficulty score (5 vs. 3, p=0.002) but longer operation time (385 vs. 245 minutes, p＜0.001). The rate of open conversion tended to be lower with RDP (3.7% vs. 14.7%, p=0.175). Conclusions In our institution practice, both RDP and LDP were safe and effective. The use of RDP appeared to be complementary to LDP, allowing us to perform more difficult procedures with comparable postoperative outcomes.

Liver resection (LR) is the main modality of treatment for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). Post-hepatectomy liver failure (PHLF) remains the most dreaded complication. We aim to create a prognostic score for early risk stratification of patients undergoing LR. Clinical and operative data of 472 patients between 2000 and 2016 with HCC or CRLM undergoing major hepatectomy were extracted and analysed from a prospectively maintained database. PHLF was defined using the 50–50 criteria. Liver cirrhosis and fatty liver were histologically confirmed in 35.6% and 53% of patients. 4.7% (n = 22) of patients had PHLF. A 90-day mortality was 5.1% (n = 24). Pre-operative albumin–bilirubin score (p = 0.0385), prothrombin time (p 7 and International Study Group for Liver Surgery criteria, intensive care unit admissions, length of stay, all complications, major complications, re-admissions and mortality (p

BACKGROUND Controversy exists regarding the safety and feasibility of minimally invasive resection for lesions in segments 7 or 8. We compare outcomes of minimally invasive surgery (MIS) and Open parenchymal sparing liver resections at two high-volume centers. METHODS From 2003 to 2016 we identified patients who underwent MIS or Open resections for lesions in segments 7 or 8 at two institutions (MSKCC and SGH). Outcomes were compared using univariate and multivariate analyses. RESULTS Two-hundred and forty-five patients underwent resection of lesions in segments 7 or 8 (MIS 30% and Open 70%). Compared to the Open group, the MIS group had longer operative time (223 ± 88 vs 188 ± 72 minutes, P = .003), lower blood loss (297 ± 287 vs 448 ± 670 mL, P = .03), and shorter mean length of stay (5.2 ± 7.4 vs 8.3 ± 11.7 days, P

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. With the increasing incidence of ICC over the past two decades in Asia, it is essential to differentiate between HCC and ICC. However, ICC may mimic the radiological appearance of HCC on computed tomography scans (CT) and magnetic resonance imaging (MRI), leading to misdiagnosis of ICC. The objective of this study is to evaluate and describe the association of specific pre-operative imaging characteristics (arterial enhancement, portal venous washout) in patients with histologically proven resected ICC in our centre. Data on patients with histology-proven ICC and mixed hepatocellular-cholangiocarcinomas (HCC-CC) who had undergone surgical resection at Singapore General Hospital (SGH) were identified from a prospectively maintained database. Pre-operative cross-sectional imaging reports were analysed. Ninety-one patients underwent resection between 1 January 2000 and 31 December 2016. Among those with no risk factors for HCC, a significant percentage of patients with ICC (24.3%) show imaging characteristics of both arterial phase hyperenhancement and non-peripheral venous washout. Among patients with risk factors for HCC, between 20.0 and 33.3% of patients with pure ICC fulfilled the imaging criteria for HCC, and this proportion was generally even higher in the mixed HCC-CC group. A significant proportion of patients with pure ICC showed pre-operative imaging characteristics which fulfilled the diagnostic criteria for HCC. The differential of ICC should be borne in mind in populations where both malignancies are endemic.

Long non-coding RNAs (lncRNAs) are often aberrantly expressed in Hepatocellular Carcinoma (HCC). We hypothesize that lncRNAs modulate HCC prognoses through differential deregulation of key lncRNAs affecting important gene network in key cancer pathways associated with pertinent clinical phenotype. Here, we present a novel approach integrating lncRNA-mRNA expression profiles with clinical characteristics to identify lncRNA signatures in clinically-relevant co-expression lncRNA-mRNA networks residing in pertinent cancer pathways. Notably one network, associated with poorer prognosis, comprises five up-regulated lncRNAs significantly correlated (|Pearson Correlation Coefficient|≥ 0.9) with 91 up-regulated genes in the cell-cycle and Rho-GTPase pathways. All 5 lncRNAs and 85/91 (93.4%) of the correlated genes were significantly associated with higher tumor-grade while 3/5 lncRNAs were also associated with no tumor capsule. Interestingly, 2/5 lncRNAs that are correlated with numerous genes in this oncogenic network were experimentally shown to up-regulate genes involved in cell-cycle and transcriptional regulation. Another network comprising 4 down-regulated lncRNAs and 8 down-regulated metallothionein-family genes are significantly associated with tumor invasion. The identification of these key lncRNAs signatures that deregulate important network of genes in key cancer pathways associated with pertinent clinical phenotype may facilitate the design of novel therapeutic strategies targeting these ‘master’ regulators for better patient outcome.

Pancreatic neuroendocrine neoplasms (PNENs) are increasingly prevalent with modern imaging, and surgical excision remains mainstay of treatment. This study aims to perform a propensity-score-matched (PSM) comparison of perioperative and oncologic outcomes following minimally invasive pancreatectomy (MIP) versus open pancreatectomy (OP) for PNEN. A retrospective review was performed on patients who underwent curative-intent surgery for PNEN at Singapore General Hospital from 1997 to 2018. A 1:1 PSM was performed between MIP and OP, after which both groups were balanced for baseline variables. We studied 134 patients who underwent surgery (36 MIP and 98 OP) for PNEN. Propensity-score-matched comparison between 35 MIP and 35 OP patients revealed that the MIP group had a longer operating time (MD = 75.0, 95% CI 15.2 to 134.8, P = 0.015), lower intraoperative blood loss (MD = − 400.0, 95% CI − 630.5 to − 169.5, P = 0.001), shorter median postoperative stay (MD = − 1.0, 95% CI − 1.9 to − 0.1, P = 0.029) and shorter median time to diet (MD = − 1.0, 95% CI − 1.9 to − 0.1, P = 0.039). There were no differences between both groups for short-term adverse outcomes and oncologic clearance. Overall survival (HR = 0.84, 95% CI 0.28 to 2.51, P = 0.761) and disease-free survival (HR = 0.57, 95% CI 0.20 to 1.64, P = 0.296) were comparable. MIP is a safe and feasible approach for PNEN and is associated with a lower intraoperative blood loss, decreased postoperative stay and time to oral intake, at the expense of a longer operative time compared to OP.

Introduction: This study aims to evaluate the impact of first assistant surgeon experience on the outcomes of laparoscopic hepatectomies in a university-affiliated teaching hospital. Methods: This ...