Intraoperative blood transfusion does not impact overall and recurrence-free survival after curative hepatectomy for hepatocellular carcinoma: A propensity-score-matched and inverse probability of treatment-weighted study.

INTRODUCTION: 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). METHODOLOGY: 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. RESULTS: 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. CONCLUSION: Intraoperative blood transfusion had no significant impact on the survival outcomes in patients who receive curative resection in primary HCC.

Impact of liver cirrhosis on the difficulty of minimally-invasive liver resections: a 1:1 coarsened exact-matched controlled study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 < 0.001), blood loss (607 vs 314 mls, p = 0.002), transfusion rate (22% vs 9%, p = 0.001), need for application of Pringles maneuver (51% vs 34%, p = 0.010), postoperative stay (6 vs 4.5 days, p = 0.004) and postoperative morbidity (26% vs 13%, p = 0.029). CONCLUSION: The presence of liver cirrhosis affected both the intraoperative technical difficulty and postoperative outcomes of MILR and hence should be considered an important parameter to be included in future difficulty scoring systems for MILR.

Pre-operative Imaging Characteristics in Histology-Proven Resected Intrahepatic Cholangiocarcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Changing trends and outcomes associated with the adoption of minimally invasive pancreatic surgeries: A single institution experience with 150 consecutive procedures in Southeast Asia.

BACKGROUND: Minimally invasive pancreatic surgeries (MIPS) are increasingly adopted worldwide. However, it remains uncertain if these reported experiences are reproducible throughout the world today. This study examines the safety and evolution of MIPS at a single institution in Southeast Asia. METHODS: This is a retrospective review of 150 consecutive patients who underwent MIPS between 2006 and 2018 of which 135 cases (90%) were performed since 2012. To determine the evolution of MIPS, the study population was stratified into 3 equal groups of 50 patients. Comparison was also made between pancreatoduodenectomies (PD), distal pancreatectomies (DP) and other pancreatic surgeries. RESULTS: One hundred and fifty patients underwent MIPS (103 laparoscopic, 45 robotic and 2 hand-assisted). Forty-three patients underwent PD, 93 DP and 14 other MIPS. There were 21 (14.0%) open conversions. There was an exponential increase in caseload over the study period. Comparison across the 3 time periods demonstrated that patients were significantly more likely to have a higher American Society of Anesthesiologists score, older, undergo PD and a longer operation time. The conversion rate decreased from 28% to 0% and increased again to 14% across the 3 time periods. Comparison between the various types of MIPS demonstrated that patients who underwent PD were significantly older, more likely to have symptomatic tumours, had longer surgery time, increased blood loss, increased frequency of extended pancreatectomies, increased frequency of hybrid procedures, longer post-operative stay, increased post-operative morbidity rate and increased post-operative major morbidity rate. CONCLUSION: The case volume of MIPS increased rapidly at our institution over the study period. Furthermore, although the indications for MIPS expanded to include more complex procedures in higher risk patients, there was no change in key perioperative outcomes.

Changing trends and outcomes associated with the adoption of minimally invasive hepatectomy: a contemporary single-institution experience with 400 consecutive resections.

BACKGROUND: Several studies published mainly from pioneers and early adopters have documented the evolution of minimally invasive hepatectomy (MIH). However, questions remain if these reported experiences are applicable and reproducible today. This study examines the changing trends, safety, and outcomes associated with the adoption of MIH based on a contemporary single-institution experience. METHODS: This is a retrospective review of 400 consecutive patients who underwent MIH between 2006 and 2017 of which 360 cases (90%) were performed since 2012. To determine the evolution of MIH, the study population was stratified into four equal groups of 100 patients. Analyses were also performed of predictive factors and outcomes of open conversion. RESULTS: Four hundred patients underwent MIH of which 379 (94.8%) were totally laparoscopic/robotic. Eighty-eight (22.0%) patients underwent major hepatectomy and 160 (40.0%) had resection of tumors located in the posterosuperior segments. There were 38 (9.5%) open conversions. Comparison across the four groups demonstrated that patients were older, had higher ASA score, and had increased frequency of previous abdominal surgery and repeat liver resections. There was also an increase in the proportion of patients who underwent totally laparoscopic/robotic surgery, major liver resection, resection of ≥ 3 segments, and multiple resections. Comparison of outcomes demonstrated that there was a significant decrease in open conversion rate, longer operation time, and increased use of Pringles maneuver. The presence of cirrhosis and institution experience (1st 100 cases) were independent predictors of open conversion. Patients who required open conversion had significantly increased operation time, blood loss, blood transfusion rate, morbidity, and mortality. CONCLUSION: The case volume of MIH performed increased rapidly at our institution over time. Although the indications of MIH expanded to include higher risk patients and more complex hepatectomies, there was a decrease in open conversion rate and no change in other perioperative outcomes.

Perioperative Outcomes of Laparoscopic Minor Hepatectomy for Hepatocellular Carcinoma in the Elderly.

INTRODUCTION: This study aims to evaluate the safety and feasibility of laparoscopic minor hepatectomy (LMH) in elderly patients with hepatocellular carcinoma (HCC). METHODS: A total of 40 consecutive elderly (≥ 70 years) patients were compared with 94 young patients (< 70 years). The 40 patients were also compared with 85 consecutive elderly patients who underwent open minor hepatectomies (OMH). After 1:1 propensity-score matching (PSM), 32 LMHs were compared with 32 OMHs in elderly patients. RESULTS: Comparison between the baseline characteristics of elderly and young HCC patients showed that elderly patients were significantly more likely to have comorbidities, ASA score > 2, non-hepatitis B, previous liver resection and larger tumor size. Comparison between perioperative outcomes demonstrated that elderly patients were significantly more likely to have a longer operation time, increased blood loss, increased need for blood transfusion, longer Pringles duration and longer postoperative stay. Comparison between LMH and OMH in elderly patients demonstrated no significant difference in baseline characteristics except the LMH cohort were significantly more likely to have > 1 comorbidity, higher platelet count and lower median AFP level. Comparison between outcomes before and after PSM demonstrated that LMH was associated with longer operation time, increased blood loss, longer Pringles duration but decreased postoperative pulmonary complications and shorter postoperative stay compared to OMH. CONCLUSION: LMH is safe and feasible in elderly patients with HCC. However, LMH in elderly patients is associated with poorer perioperative outcomes compared to LMH in young patients. Comparison between LMH and OMH in elderly patients demonstrated advantages in terms of decreased pulmonary complications and shorter length of stay at the expense of increased operation time and blood loss.

Early experience with pure laparoscopic donor hepatectomy: comparison with open donor hepatectomy and non-donor laparoscopic hepatectomy.

BACKGROUND: Pure laparoscopic donor hepatectomy (L-DH) has seen a rise in uptake in recent years following the popularization of minimally invasive modality for major hepatobiliary surgery. Our study aimed to determine the safety and compare the perioperative outcomes of L-DH with open donor hepatectomy (O-DH) and laparoscopic non donor hepatectomy (L-NDH) based on our single institution experience. METHODS: Eighty of 113 laparoscopic hemi-hepatectomies performed between 2015 and 2022 met study inclusion criteria. Of these, 11 were L-DH. PSM in a 1:2 ratio of L-DH versus L-NDH and 1:1 ratio of L-DH versus O-DH were performed, identifying patients with similar baseline clinicopathological characteristics. RESULTS: After 2:1 matching, the L-DH cohort were significantly younger (P < 0.001) and had lower ASA scores (P < 0.001) than the L-NDH cohort. L-DH was associated with a longer median operating time (P < 0.001) and shorter median postoperative stay (P < 0.001) than L-NDH. After 1:1 matching, there were no significant differences in baseline demographic between the L-DH and O-DH cohorts. L-DH was associated with lower median blood loss (P = 0.040) and shorter length of stay compared to O-DH (P = 0.004). There were no significant differences in recipient outcomes for both cohorts. CONCLUSION: L-DH can be adopted safely by surgeons experienced in L-NDH and ODH. It is associated with decreased blood loss and shorter length of stay compared to O-DH.

Metroticket approach in a retrospective cohort study to predict overall survival after surgical resection for intermediate stage hepatocellular carcinoma.

BACKGROUND: Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC) patients meeting the Milan criteria as well as a widely used therapy in intermediate-stage HCC. However, intermediate-stage HCC encompasses a wide spectrum of disease and there is a lack of good predictive models for the long-term clinical outcome of HCC patients currently. Here, we adopt Mazzaferro's Metroticket 2.0 to create a robust survival prediction model for intermediate-stage HCC patients undergoing surgical resection. Our algorithm considers age, AFP levels, ALBI score, and nodule size/number to generate survival estimates in an accessible graph format. Importantly, our model surpasses the American Joint Committee on Cancer staging model and was validated with independent US patient data. METHODS: We conducted a retrospective analysis of OS and RFS in early- and intermediate-stage HCC patients treated with liver resection, including a training cohort in Singapore and a validation cohort in North Carolina, USA. RESULTS: We recorded 278 deaths (35.0%) and 428 patients (53.9%) in the first 5-years after surgical resection; higher ALBI score, higher lnAFP, more advanced age and higher tumour burden index were identified as significant parameters. The overall predictive capability of our model, with the inclusion of AFP, is reflected with a UNO's C-statistic of 0.655, which is 1.11 times better than the 0.5895 C-statistic of the 8th AJCC TNM Staging model. CONCLUSIONS: Our modified Metroticket model allows for more granular and better-informed prognostication. This will help surgeons and patients make accurate comparisons between the clinical outcomes of surgical resection and other non-surgical treatments.

Preoperative Predictors of Early Recurrence After Liver Resection for Multifocal Hepatocellular Carcinoma.

BACKGROUND: Liver transplantation remains the optimal treatment for multifocal hepatocellular carcinoma (HCC). However, due to resource constrains, other therapeutic modalities such as liver resection (LR), are frequently utilized. LR, however, has to be balanced against potential morbidity and mortality along with the risks of early recurrence leading to futile surgery. In this study, we evaluated preoperative factors, including inflammatory indices, in predicting early (< 1 year) recurrence in patients who underwent LR for multifocal HCC. METHODS: This was a post hoc analysis of 250 consecutive patients with multifocal HCC who underwent LR. RESULTS: After exclusion of 10 patients with 30-day/in-hospital mortality, 240 were included of which 134 (55.8%) developed early recurrence. Hepatitis B/C aetiology, 3/ > more hepatic nodules and elevated alpha-fetoprotein (AFP) ≥ 200 ng/ml were significant independent preoperative predictors of early recurrence. The early recurrence rate was 72.1% when 2 out of 3 significant predictive factors were present. The conglomerate of all 3 factors predicted early recurrence of 100% with a statistically significant association between number of predictive factors and early recurrence (p < 0.001). CONCLUSION: Better patient selection via the use of preoperative predictive factors of early recurrence such as hepatitis B/C aetiology, ≥ 3 nodules and elevated AFP ≥ 200 ng/ml may assist in identifying patients in whom LR is deemed futile and improve resource allocation.

Poor utility of current nomograms assessing the risk of intraoperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma and proposal of a new model.

BACKGROUND: 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. METHODS: 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. RESULTS: 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) (P < .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). CONCLUSION: 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.

Effect of age on the short- and long-term outcomes of patients undergoing curative liver resection for HCC.

BACKGROUND: Few studies have evaluated the outcomes of curative liver resection (LR) in octogenarian patients, analysed cancer-specific survival (CSS) with HCC-related death or explored the age-varying effect of HCC-related death in elderly patients undergoing LR. We aim to determine the effect of age on the short and long-term outcomes of LR for HCC. METHODOLOGY: Between 2000 and 2018, 1,092 patients with primary HCC who underwent LR with curative intent were retrospectively reviewed. The log-rank test and Gray's test were used to assess the equality of survivor functions and competing risk-adjusted cumulative incidence functions between patients in the three age categories respectively. Regression adjustment was used to control for confounding bias via a Principal Component Analysis. Quantile, Firth logistic, Cox, and Fine-Gray competing risk regression were used to analyse continuous, binary, time-to-event, and cause-specific survival respectively. Restricted cubic splines were used to illustrate the dose-effect relationship between age and patient outcomes. RESULTS: The study comprised of 764 young patients (<70 years), 278 septuagenarians (70-79 years old) and 50 octogenarians (≥80 years). Compared to young patients, octogenarians had significantly lower 5-year OS(62.1% vs 37.7%, p < 0.001). However, there was no significant difference in 1-year RFS(73.1% vs 67.0%, p = 0.774) or 5-year CSS (5.4% vs 15.2%, p = 0.674). Every 10-year increase in age was significantly associated with an increase length of stay (p < 0.001), postoperative complications (p = 0.004) and poorer OS(p = 0.018) but not significantly associated with major complications (p = 0.279), CSS(p = 0.338) or RFS(p = 0.941). CONCLUSION: Age by itself was associated with OS after LR for HCC but was not a significant risk factor for HCC-related death.

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.

Impact of COVID-19 on Liver Transplantation in Hong Kong and Singapore: A Modelling Study.

BACKGROUND: Liver transplantation (LT) activities during the COVID-19 pandemic have been curtailed in many countries. The impact of various policies restricting LT on outcomes of potential LT candidates is unclear. METHODS: We studied all patients on the nationwide LT waitlists in Hong Kong and Singapore between January 2016 and May 2020. We used continuous time Markov chains to model the effects of different scenarios and varying durations of disruption on LT candidates. FINDINGS: With complete cessation of LT, the projected 1-year overall survival (OS) decreased by 3•6%, 10•51% and 19•21% for a 1-, 3- and 6-month disruption respectively versus no limitation to LT, while 2-year OS decreased by 4•1%, 12•55%, and 23•43% respectively. When only urgent (acute-on-chronic liver failure [ACLF] or acute liver failure) LT was allowed, the projected 1-year OS decreased by a similar proportion: 3•1%, 8•41% and 15•20% respectively. When deceased donor LT (DDLT) and urgent living donor LT (LDLT) were allowed, 1-year projected OS decreased by 1•2%, 5•1% and 8•85% for a 1-, 3- and 6-month disruption respectively. OS was similar when only DDLT was allowed. Complete cessation of LT activities for 3-months resulted in an increased projected incidence of ACLF and hepatocellular carcinoma (HCC) dropout at 1-year by 49•1% and 107•96% respectively. When only urgent LT was allowed, HCC dropout and ACLF incidence were comparable to the rates seen in the scenario of complete LT cessation. INTERPRETATION: A short and wide-ranging disruption to LT results in better outcomes compared with a longer duration of partial restrictions. FUNDING: None to disclose.

Preoperative predictors of early recurrence of AJCC T4 hepatocellular carcinoma.

BACKGROUND: The management of HCC differs depending on the extent of disease. Surgery may be offered in selected cases of T4 disease as defined by AJCC 8th. However, outcome data post partial hepatectomy (PH) for T4 disease is scarce. We sought to evaluate the outcomes of patients post resection of T4 HCC and assess preoperative predictive factors of early recurrence. METHODS: We performed a retrospective review of 235 consecutive patients who underwent resection for T4 HCC from 2001 to 2018 at our institution. RESULTS: Median overall survival was 35.9 months (95% CI 25.7-46.0). 109 patients (49.5%) developed recurrence, of which 94 patients (42.7%) experienced early recurrence within 12 months. Median time to recurrence was 38.1 months. Multivariate analysis demonstrated that vascular invasion were significant independent preoperative predictor of early recurrence post resection. Patients who experienced early recurrence had a significantly shorter median overall survival 14.3 months (95% CI 25.7-46.0) compared to those who did not (55.5 months, 95% CI 40.6-70.8, p = .000). CONCLUSION: Selected patients with T4 HCC may benefit from PH. Macrovascular invasion was associated with early recurrence within 12 months.

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.

Time-varying prognostic effects of primary tumor sidedness and grade after curative liver resection for colorectal liver metastases.

BACKGROUND: The veracity of the proportional hazards (PH) requirement is rarely scrutinized in most areas of cancer research, although fulfilment of this assumption underpins widely-used Cox survival models. We sought to critically appraise the existence of prognostic factors with time-dependent effects and to characterize their impact on survival among CLM patients. METHODS: Consecutive patients who underwent liver resection with curative intent for CLM at the Singapore General Hospital were identified from a prospectively-maintained database. We evaluated PH of 55 candidate variables, and parameters which departed significantly from proportionality were included in Cox models that incorporated an interaction term to account for time-dependent effects. As sensitivity analyses, we fitted Weibull mixture 'cure' models to handle long plateaus in the tails of survival curves, and also analyzed the restricted mean survival time. RESULTS: 318 consecutive patients who underwent curative liver resection for CLM between Jan 2000 and Nov 2016 were included in this analysis. Hazard ratios for tumor grade (poorly-versus well- and moderately-differentiated) were found to decrease from 3.135 (95% CI: 1.637-6.003) at 12 months to 2.048 (95% CI: 1.038-4.042) after 24 months, and ceased to be significant at 26 months. Compared to left-sided tumors, a right-sided tumor location was found to portend worse prognosis for the first 10 months after resection but subsequently confer a survival benefit due to a crossing of survival curves. Corroborating this observation, long-term cure fractions were estimated to be 25.5% (95% CI: 17.4%-33.6%) and 34.2% (95% CI: 17.4%-50.9%) among patients with left-sided and right-sided primary disease respectively. CONCLUSION: Primary tumor sidedness and grade appear to exert time-varying prognostic effects in CLM patients undergoing curative liver resection.

Continuous improvements in short and long-term outcomes after partial hepatectomy for hepatocellular carcinoma in the 21st century: Single institution experience with 1300 resections over 18 years.

INTRODUCTION: To investigate the changing trends in short- and long-term outcomes after partial hepatectomy(PH) for hepatocellular carcinoma(HCC) performed in the 21st century. METHODS: A retrospective review was conducted on 1300 consecutive patients who underwent PH for HCC. The study cohort was divided into 3 time periods(P): P1(2000-2005), P2(2006-2011) and P3(20012-2017). RESULTS: Comparison between the patients' baseline demographic features across the 3 periods demonstrated that patients were significantly older, had decreasing frequency of hepatitis B, increasing non-alcoholic fatty liver disease, lower alpha-feto protein(AFP) level, lower creatinine levels, less likely to undergo emergency surgery, less likely to undergo major hepatectomy, more likely to undergo repeat resection and minimally-invasive surgery. There was also an increase in operation time, decrease in blood loss, increase frequency in the use of Pringles manoeuvre, decrease liver failure, decrease length of stay and decrease postoperative mortality. HCC resected were of smaller size, less likely to demonstrate microvascular invasion and less likely to have close margins. This was associated with significant improvement in overall survival and recurrence free interval over time. Period of resection was an independent predictor of 90-day mortality and OS on multivariate analysis. CONCLUSION: We observed a continuous improvement in postoperative outcomes including postoperative mortality and long-term survival after PH for HCC over the past 18 years.

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.

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.