Defining Global Benchmarks for Laparoscopic Right Posterior Sectionectomy/H67: An International Multicenter Study.

OBJECTIVE: We aimed to establish global benchmark outcomes indicators for L-RPS/H67. BACKGROUND: Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted. METHODS: This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff. RESULTS: There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively. CONCLUSIONS: The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking.

Impact of body mass index on the difficulty and outcomes of laparoscopic left lateral sectionectomy.

INTRODUCTION: Currently, the impact of body mass index (BMI) on the outcomes of laparoscopic liver resections (LLR) is poorly defined. This study attempts to evaluate the impact of BMI on the peri-operative outcomes following laparoscopic left lateral sectionectomy (L-LLS). METHODS: A retrospective analysis of 2183 patients who underwent pure L-LLS at 59 international centers between 2004 and 2021 was performed. Associations between BMI and selected peri-operative outcomes were analyzed using restricted cubic splines. RESULTS: A BMI of >27kg/m2 was associated with increased in blood loss (Mean difference (MD) 21 mls, 95% CI 5-36), open conversions (Relative risk (RR) 1.13, 95% CI 1.03-1.25), operative time (MD 11 min, 95% CI 6-16), use of Pringles maneuver (RR 1.15, 95% CI 1.06-1.26) and reductions in length of stay (MD -0.2 days, 95% CI -0.3 to -0.1). The magnitude of these differences increased with each unit increase in BMI. However, there was a "U" shaped association between BMI and morbidity with the highest complication rates observed in underweight and obese patients. CONCLUSION: Increasing BMI resulted in increasing difficulty of L-LLS. Consideration should be given to its incorporation in future difficulty scoring systems in laparoscopic liver resections.

Defining Global Benchmarks for Laparoscopic Liver Resections: An International Multicenter Study.

OBJECTIVE: To establish global benchmark outcomes indicators after laparoscopic liver resections (L-LR). BACKGROUND: There is limited published data to date on the best achievable outcomes after L-LR. METHODS: This is a post hoc analysis of a multicenter database of 11,983 patients undergoing L-LR in 45 international centers in 4 continents between 2015 and 2020. Three specific procedures: left lateral sectionectomy (LLS), left hepatectomy (LH), and right hepatectomy (RH) were selected to represent the 3 difficulty levels of L-LR. Fifteen outcome indicators were selected to establish benchmark cutoffs. RESULTS: There were 3519 L-LR (LLS, LH, RH) of which 1258 L-LR (40.6%) cases performed in 34 benchmark expert centers qualified as low-risk benchmark cases. These included 659 LLS (52.4%), 306 LH (24.3%), and 293 RH (23.3%). The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, and 90-day mortality after LLS, LH, and RH were 209.5, 302, and 426 minutes; 2.1%, 13.4%, and 13.0%; 3.2%, 20%, and 47.1%; 0%, 7.1%, and 10.5%; 11.1%, 20%, and 50%; 0%, 7.1%, and 20%; and 0%, 0%, and 0%, respectively. CONCLUSIONS: This study established the first global benchmark outcomes for L-LR in a large-scale international patient cohort. It provides an up-to-date reference regarding the "best achievable" results for L-LR for which centers adopting L-LR can use as a comparison to enable an objective assessment of performance gaps and learning curves.

Association of standardized liver volume and body mass index with outcomes of minimally invasive liver resections.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of introduction of an enhanced recovery protocol on the outcomes of laparoscopic liver resections: A propensity-score matched study.

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.

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.

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.

Repeat hepatectomy versus radiofrequency ablation in management of recurrent hepatocellular carcinoma: an average treatment effect analysis.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: RH confers a late survival benefit compared with RFA for patients with recurrent HCC despite a higher morbidity rate.

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.

Outcome of minimally invasive liver resection for extrapancreatic biliary malignancies: A single-institutional experience.

BACKGROUND: Minimally invasive liver resection (MILR) has been increasingly adopted over the past decade, and its application has been expanded to the management of extrapancreatic biliary malignancies (EPBMs). We aimed to evaluate the peri- and post-operative outcome of patients undergoing MILR for suspected EPMB. METHODS: Forty-four consecutive patients who underwent MILR with a curative intent for EPBM at Singapore General Hospital between 2011 and 2018 were identified from a prospectively maintained surgical database. Clinical and operative data were analysed and compared to provide information and make comparisons on peri- and post-operative outcomes. RESULTS: A total of 26, 5 and 13 patients underwent MILR for intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PHC) and gallbladder carcinoma (GBCA), respectively. Six major hepatectomies were performed, of which one was laparoscopic assisted and another was robot assisted. Ten patients underwent posterosuperior segmentectomies. There was one open conversion. The mean operative time was 266.5 min, and the mean blood loss was 379 ml. The mean length of hospital stay was 4.7 days with no incidences of 30- and 90-day mortality. The rate of recurrence-free survival (RFS) was 75% (at least 12-month follow-up). There was a significantly higher rate of robot-assisted procedures in patients undergoing MILR for GBCA/PHC as compared to ICC (P = 0.034). Patients undergoing posterosuperior segmentectomies required longer operative time (P = 0.018) with an increased need for (P = 0.001) and duration of (P = 0.025) Pringles manoeuvre. There were no differences in operative time, blood loss, morbidity, mortality or RFS between the above groups. CONCLUSION: Minimally invasive surgery can be adopted safely with a low open conversion rate for EPBMs.

Changing trends and outcomes associated with the adoption of minimally-invasive pancreato-biliary surgery: Contemporary experience of a 'self-taught' early adopter in Southeast Asia.

BACKGROUND: Minimally-invasive pancreato-biliary surgery (MIPBS) is increasingly reported worldwide. This study examines the changing trends, safety and outcomes associated with the adoption of MIPBS based on a contemporary experience of an early adopter in Southeast Asia. METHODS: Retrospective review of 114 consecutive patients who underwent MIPBS by a single surgeon over 86 months from 2011. The study population was stratified into three equal groups of 38 patients. Comparison was also performed between minimally-invasive pancreato surgery (MIPS) and minimally-invasive biliary surgery (MIBS). RESULTS: There were 70 MIPS and 44 MIBS. Sixty-three cases (55.3%) were performed using robotic assistance and fourteen (12.3%) were hybrid procedures with open reconstruction. Forty-four (38.6%) procedures were performed for malignancy. There were 8 (7.0%) open conversions and median operation time was 335 (range, 60-930) min. There were nine extended pancreatectomies including seven involving vascular reconstructions. Major morbidity (>Grade 2) occurred in 20 (17.5%) patients including 6 (5.3%) reoperations and there was no mortality. Comparison across the three groups demonstrated that with increasing experience, there was a significant trend in a higher proportion of higher ASA score patients, increasing frequency of procedures requiring anastomosis and increasing the use of robotic assistance without significant difference in key perioperative outcomes such as open conversion rate, morbidity and hospital stay. Comparison between MIPS and MIBS demonstrated that MIPS was associated with significantly longer operation time, increased blood loss, increased transfusion rate, longer hospital stay, increased readmission rate and increased morbidity. CONCLUSION: MIPBS can be safely adopted today with a low open conversion rate.

Preoperative Predictors Including the Role of Inflammatory Indices in Predicting Early Recurrence After Re-resection for Recurrent Hepatocellular Carcinoma.

BACKGROUND: Repeat liver resection (RLR) for recurrent HCC (rHCC) is a widely accepted treatment modality. However, early recurrence rate is high, frequently resulting in futile resection. We performed this study to evaluate preoperative factors, including the value of inflammatory indices, in predicting early (<1 year) recurrence in patients who underwent RLR for rHCC. This may help clinicians better select patients for RLR, while excluding cases in which RLR for rHCC would likely be futile. METHODS: This is a retrospective study of 80 patients where 90 operative cases of RLR and 84 cases of early recurrence (<1 year) post-RLR were evaluated. Preoperative predictors of early recurrence and overall survival (OS) were assessed. RESULTS: There were 31 (34.4%) early recurrences with a 5-year OS of 38.9%. Elevated platelet-to-lymphocyte ratio (PLR) >103.6 was a significant independent preoperative predictor of both early recurrence, relative risk (RR) 4.284 (P = 0.001) and OS, RR 2.139 (P = 0.027), while alphafetoprotein (AFP) ≥ 200 was a significant independent preoperative predictor of early recurrence only, RR 11.655 (P = 0.030). Patients were followed-up at a median of 14.3 months with 54.8% developing intrahepatic recurrences and 19.4% developing extrahepatic recurrences. CONCLUSION: Both, elevated PLR and AFP ≥ 200 were independent predictors of early (<1 year) recurrence after RLR for rHCC, while only an elevated PLR was an independent preoperative prognosticators of overall survival. Indication for RLR should be carefully discussed in patients with relapsed HCC with an elevated PLR, due to the potential of early recurrence and poor overall survival.

Impact of spontaneous rupture on the survival outcomes after liver resection for hepatocellular carcinoma: A propensity matched analysis comparing ruptured versus non-ruptured tumors.

INTRODUCTION: Spontaneous rupture of HCC (srHCC) is a life-threatening sequela of HCC characterized by a high mortality. Liver resection (LR) is the ideal therapeutic strategy as it not only arrests hemorrhage but also remove the offending tumour. We sought to determine the impact of spontaneous rupture on the survival outcomes of patients after LR by performing a propensity score matched (PSM) analysis comparing patients who underwent LR for srHCC versus non-ruptured (nrHCC). METHODS: From 2000 to 2015, a total of 67 patients who underwent LR for srHCC which met the study criteria were included. 1:2 PSM was performed comparing 49 of 67 patients with srHCC with 98 nrHCC selected from a cohort of 724 patients who underwent LR during the study period. RESULTS: Median survival following LR for srHCC was 21.9 months, while 5-year overall survival (OS) and disease-free survival (DFS) was 43.1% and 19.4% respectively. After 1:2 PSM analysis, there was no significant difference between LR for srHCC (n = 49) versus nrHCC (n-98) in terms of OS [21.9 (interquartile range (IQR), 11.8-44.0 vs 27.4 (IQR, 6.9-57.8) months, HR 1.02, CI 0.63-1.66, p = 0.94], DFS [11.8 (IQR, 5.6-25.6) vs 13.77 (IQR,4.5-34.9) HR 0.74, CI 0.54-1.02, p = 0.06] and length of stay [8 (IQR, 7-11) vs 7 (IQR, 6-10) HR 0.93, CI 0.0.68-1.29), p = 0.68]. CONCLUSION: LR for clinically stable patients with srHCC provides survival and recurrence outcomes that are comparable to patients with nrHCC.

Pre-operative predictors of early recurrence/mortality including the role of inflammatory indices in patients undergoing partial hepatectomy for spontaneously ruptured hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Spontaneous rupture of Hepatocellular Carcinoma (srHCC) is a life-threatening emergency. We sought to identify the pre-operative predictors of early tumor recurrence/mortality including the role of inflammatory indices after partial hepatectomy for srHCC. METHODS: Between 2000-2015, 79 patients with srHCC were identified to have undergone upfront partial hepatectomy following srHCC. Clinicopathologic data were retrospectively analyzed to identify pre-operative predictors of early (<1 year) recurrence and mortality. RESULTS: Seventy-nine patients were identified to have undergone partial hepatectomy for srHCC. The 1-year mortality and 1-year recurrence rate in our series was 30.3% and 41.8% respectively. On multivariate analyses, free tumor rupture and a tumor size > 10 cm were identified to be independent predictors of early recurrence while an alpha fetoprotein (AFP) > 200 ng/mL was an independent predictor of early mortality. Neutrophil-to-lymphocyte ratio > 3 and prognostic nutritional index < 40 were predictors of early recurrence while PLR > 180 was a predictor of early mortality on univariate analyses but not multivariate analyses. CONCLUSIONS: Tumor size > 10 cm, free tumor rupture, and an AFP > 200 ng/mL were useful predictors in avoiding "futile surgery" in patients with srHCC undergoing a partial hepatectomy. Preoperative inflammatory markers appear to be less useful as predictors of early recurrence/mortality in this cohort of patients.