Impact of Liver Cirrhosis, Severity of Cirrhosis, and Portal Hypertension on the Difficulty and Outcomes of Laparoscopic and Robotic Major Liver Resections for Primary Liver Malignancies.

BACKGROUND: Minimally invasive liver resections (MILR) offer potential benefits such as reduced blood loss and morbidity compared with open liver resections. Several studies have suggested that the impact of cirrhosis differs according to the extent and complexity of resection. Our aim was to investigate the impact of cirrhosis on the difficulty and outcomes of MILR, focusing on major hepatectomies. METHODS: A total of 2534 patients undergoing minimally invasive major hepatectomies (MIMH) for primary malignancies across 58 centers worldwide were retrospectively reviewed. Propensity score (PSM) and coarsened exact matching (CEM) were used to compare patients with and without cirrhosis. RESULTS: A total of 1353 patients (53%) had no cirrhosis, 1065 (42%) had Child-Pugh A and 116 (4%) had Child-Pugh B cirrhosis. Matched comparison between non-cirrhotics vs Child-Pugh A cirrhosis demonstrated comparable blood loss. However, after PSM, postoperative morbidity and length of hospitalization was significantly greater in Child-Pugh A cirrhosis, but these were not statistically significant with CEM. Comparison between Child-Pugh A and Child-Pugh B cirrhosis demonstrated the latter had significantly higher transfusion rates and longer hospitalization after PSM, but not after CEM. Comparison of patients with cirrhosis of all grades with and without portal hypertension demonstrated no significant difference in all major perioperative outcomes after PSM and CEM. CONCLUSIONS: The presence and severity of cirrhosis affected the difficulty and impacted the outcomes of MIMH, resulting in higher blood transfusion rates, increased postoperative morbidity, and longer hospitalization in patients with more advanced cirrhosis. As such, future difficulty scoring systems for MIMH should incorporate liver cirrhosis and its severity as variables.

Value of lymph node dissection in intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to perform a systematic review and meta-analysis to investigate the impact of lymph node dissection (LND) on outcomes following resection of intrahepatic cholangiocarcinoma (ICC). METHODS: PubMed, EMBASE, and Cochrane were searched from inception to 30th January 2023 for studies that compared LND with no LND (NLND) among patients with ICC. To limit the effect of unbalanced covariates, only studies that utilized propensity score-based methods were included. Subgroup analysis of patients with clinically node-negative (cN0) ICC was analyzed. RESULTS: Among 3776 patients with ICC, individuals in the LND versus NLND cohorts had comparable overall survival (OS) (Hazard ratio [HR] 0.78, 95 % confidence interval [CI] 0.57-1.06, P = 0.11), disease-free survival (DFS) (HR 0.84, 95 % CI 0.70-1.01, P = 0.07) and risk of major complications (odds ratio [OR] 1.07, 95 % CI 0.70-1.62, P = 0.75). Subgroup analysis of cN0 patients, OS was significantly higher in patients who underwent LND (HR 0.61, 95 % CI 0.50-0.74, P < 0.01), with a non-significant trend towards improved DFS (HR 0.81, 95 % CI 0.65-1.01, P = 0.06). CONCLUSION: This study found no differences in long-term survival or morbidity following LND for ICC. Subgroup analysis of cN0 patients, who underwent LND detected improved OS with a trend towards better DFS, compared to patients with NLND.

UNOS Down-Staging Criteria for Liver Transplantation of Hepatocellular Carcinoma: Systematic Review and Meta-Analysis of 25 Studies.

BACKGROUND & AIMS: Down-staging is commonly used to select patients with hepatocellular carcinoma (HCC) beyond Milan criteria (MC) for liver transplantation (LT), but outcomes are heterogenous. We aimed to estimate pooled down-staging success rates, HCC recurrence, and overall survival (OS), stratified by criteria used for baseline tumor burden. METHODS: We searched Pubmed and EMBASE databases from inception until August 2021 for studies reporting down-staging success (reduction of tumor burden to within MC) and outcomes of adult HCC patients. In addition, we performed a pooled analysis using reconstructed individual participant data to obtain robust estimates for OS. RESULTS: We screened 1059 articles and included 25 articles involving 3997 patients. Overall, 55.16% (45.49%-64.46%) underwent successful down-staging, and 31.52% (24.03%-40.11%) received LT (by intention-to-treat analysis [ITT]). Among patients who received LT, 16.01% (11.80%-21.37%) developed HCC recurrence. Comparing studies that used the United Network for Organ Sharing Down-Staging (UNOS-DS) criteria versus studies beyond UNOS-DS or did not specify criteria, down-staging success (by ITT) was 83.21% versus 45.93%, P < .001; the proportion who received LT (by ITT) was 48.61% vs 28.60%, P = .030; and HCC recurrence (among patients who received LT) occurred in 9.06% versus 20.42%, P < .001. Among studies that used UNOS-DS criteria, ITT 1- and 5-year OS from the initiation of down-staging treatment was 86% and 58%, respectively, whereas 1- and 5-year post-LT OS was 94% and 74%, respectively. CONCLUSIONS: Among studies that adhered to UNOS-DS criteria, down-staging was successful in four-fifths of patients, >50% received LT, and post-LT outcomes were excellent. These data provide clinical validation for the utilization of UNOS-DS criteria.

Minimally Invasive Versus Open Radical Antegrade Modular Pancreatosplenectomy: A Meta-Analysis.

BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS) was introduced to improve the tangential resection margin rates and N1 node clearance following resection of malignancies of the pancreatic body and tail. Owing to its technical complexity, minimally invasive RAMPS (MI-RAMPS) has only been reported by a few centers worldwide. We performed this meta-analysis to compare both short- and long-term outcomes between open RAMPS (O-RAMPS) and minimally invasive RAMPS (MI-RAMPS). METHODS: A systematic search of the electronic databases PubMed, Medline (via PubMed), Cochrane Register of Controlled Trials (CENTRAL), EMBASE, Scopus and Web of Science was performed to identify eligible studies published in the English language regardless of study design. The outcomes of interest were operation time, estimated blood loss, transfusion rates, overall complications, Grade B/C post-operative pancreatic fistula (POPF) rates, post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), length of stay (LOS), R0 resection rates, lymph node (LN) yield and overall survival (OS). RESULTS: Five non-randomized studies comprising of a total 229 patients (89 MI-RAMPS, 140 O-RAMPS) were included for analysis. Intra-operative blood loss was observed to be significantly reduced in MI-RAMPS as compared to O-RAMPS (MD -256.16, P < 0.001), while LN yield was higher in O-RAMPS as compared to MI-RAMPS (MD -2.73, P = 0.02). There were no statistically significant differences observed for the other perioperative, oncologic and survival outcomes. CONCLUSIONS: This meta-analysis provides early evidence to suggest that MI-RAMPS may produce comparable short- and long-term outcomes to O-RAMPS, when undertaken by appropriately skilled surgeons in well-selected patients. Further large-scale prospective studies are required to corroborate these findings.

Radiofrequency Ablation Versus Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: An updated systematic review and meta-analysis was conducted to compare radiofrequency ablation (RFA) versus repeat hepatectomy (RH) for patients with recurrent hepatocellular carcinoma (rHCC) after a previous liver resection. METHODS: PubMed, EMBASE, and Cochrane databases were searched from inception to October 2021 for randomized controlled trials and propensity-score matched studies. Individual participant survival data of disease-free survival (DFS) and overall survival (OS) were extracted and reconstructed followed by one-stage and two-stage meta-analysis. Secondary outcomes were major complications and length of hospital stay (LOHS). RESULTS: A total of seven studies (1317 patients) were analysed. In both one-stage and two-stage meta-analysis, there was no significant difference in OS between the RFA and RH cohorts (Hazard Ratio (HR) 1.15, 95% CI 0.98-1.36, P = 0.094 and HR 1.12, 95% CI 0.77-1.64, P = 0.474 respectively), while the RFA group had a higher hazard rate of disease recurrence compared to the RH group (HR 1.30, 95% CI 1.13-1.50, P < 0.001 and HR 1.31, 95% CI 1.09-1.57, P = 0.013, respectively). RFA was associated with fewer major complications and shorter LOHS versus RH (Odds Ratio 0.34, 95% CI 0.15-0.76, P = 0.009 and Weighted Mean Difference - 4.78, 95% CI - 6.30 to - 3.26, P < 0.001, respectively). CONCLUSIONS: RH may be associated with superior DFS for rHCC, at the expense of higher morbidity rate and longer LOHS. However, OS is comparable between both modalities. As such, these techniques may be utilized as complementary strategies depending on individual patient and disease factors. Large-scale, randomized, prospective studies are required to corroborate these findings.

Laparoscopic versus open resection of hepatocellular carcinoma in patients with cirrhosis: meta-analysis.

BACKGROUND: The exact role of laparoscopic liver resection (LLR) in patients with hepatocellular carcinoma (HCC) and underlying liver cirrhosis (LC) is not well defined. In this meta-analysis, both long- and short-term outcomes following LLR versus open liver resection (OLR) were analysed. METHODS: PubMed, EMBASE, Scopus and Web of Science databases were searched systematically for randomised controlled trials (RCTs) and propensity-score matched (PSM) studies reporting outcomes of LLR versus OLR of HCC in patients with cirrhosis. Primary outcome was overall survival (OS). This was analysed using one-stage (individual participant data meta-analysis) and two-stage (aggregate data meta-analysis) approaches. Secondary outcomes were operation duration, blood loss, blood transfusion, Pringle manoeuvre utilization, overall and major complications, length of hospital stay (LOHS), 90-day mortality and R0 resection rates. RESULTS: Eleven studies comprising 1618 patients (690 LLR versus 928 OLR) were included for analysis. In the one-stage meta-analysis, an approximately 18.7 per cent lower hazard rate (HR) of death in the LLR group (random effects: HR 0.81, 95 per cent confidence interval [C.I.] 0.68 to 0.96; P = 0.018) was observed. Two-stage meta-analysis resulted in a pooled HR of 0.84 (95 per cent C.I. 0.74 to 0.96; P = 0.01) in the overall LLR cohort. This indicated a 16-26 per cent reduction in the HR of death for patients with HCC and cirrhosis who underwent LLR. For secondary outcomes, LLR was associated with less blood loss (mean difference [MD] -99 ml, 95 per cent C.I. -182 to -16 ml), reduced overall complications (odds ratio 0.49, 95 per cent C.I. 0.37 to 0.66) and major complications (odds ratio 0.45, 95 per cent C.I. 0.26 to 0.79), and shorter LOHS (MD -3.22 days, 95 per cent C.I. -4.38 to -2.06 days). CONCLUSION: Laparoscopic resection of HCC in patients with cirrhosis is associated with improved survival and perioperative outcomes.

Survival Advantage of Laparoscopic Versus Open Resection For Colorectal Liver Metastases: A Meta-analysis of Individual Patient Data From Randomized Trials and Propensity-score Matched Studies.

OBJECTIVE: To perform an individual participant data meta-analysis using randomized trials and propensity-score matched (PSM) studies which compared laparoscopic versus open hepatectomy for patients with colorectal liver metastases (CLM). BACKGROUND: Randomized trials and PSM studies constitute the highest level of evidence in addressing the long-term oncologic efficacy of laparoscopic versus open resection for CLM. However, individual studies are limited by the reporting of overall survival in ways not amenable to traditional methods of meta-analysis, and violation of the proportional hazards assumption. METHODS: Survival information of individual patients was reconstructed from the published Kaplan-Meier curves with the aid of a computer vision program. Frequentist and Bayesian survival models (taking into account random-effects and nonproportional hazards) were fitted to compare overall survival of patients who underwent laparoscopic versus open surgery. To handle long plateaus in the tails of survival curves, we also exploited "cure models" to estimate the fraction of patients effectively "cured" of disease. RESULTS: Individual patient data from 2 randomized trials and 13 PSM studies involving 3148 participants were reconstructed. Laparoscopic resection was associated with a lower hazard rate of death (stratified hazard ratio = 0.853, 95% confidence interval: 0.754-0.965, P = 0.0114), and there was evidence of time-varying effects (P = 0.0324) in which the magnitude of hazard ratios increased over time. The fractions of long-term cancer survivors were estimated to be 47.4% and 18.0% in the laparoscopy and open surgery groups, respectively. At 10-year follow-up, the restricted mean survival time was 8.6 months (or 12.1%) longer in the laparoscopy arm (P < 0.0001). In a subgroup analysis, elderly patients (≥65 years old) treated with laparoscopy experienced longer 3-year average life expectancy (+6.2%, P = 0.018), and those who live past the 5-year milestone (46.1%) seem to be cured of disease. CONCLUSIONS: This patient-level meta-analysis of high-quality studies demonstrated an unexpected survival benefit in favor of laparoscopic over open resection for CLM in the long-term. From a conservative viewpoint, these results can be interpreted to indicate that laparoscopy is at least not inferior to the standard open approach.

Early experience with laparoscopic liver resection for spontaneously ruptured hepatocellular carcinoma.

INTRODUCTION: There are limited data to date regarding laparoscopic liver resection (LLR) for spontaneously ruptured hepatocellular carcinoma (srHCC). We performed this study to determine the safety and feasibility of LLR for srHCC. MATERIALS AND METHODS: We conducted a retrospective review of all patients who underwent liver resection for srHCC from 2000 to 2018. A total of five patients underwent LLR for srHCC, and they were matched to 10 patients who underwent open liver resection (OLR) for srHCC to perform a 1:2 comparison. A separate cohort of patients who underwent LLR for non-ruptured HCC (nrHCC) was also compared against the laparoscopic group. RESULTS: The comparison between LLR versus OLR for srHCC demonstrated no significant differences in baseline characteristics between both groups. There was also no significant difference in perioperative outcomes such as median operating time, estimated blood loss (EBL), rate of blood transfusion, post-operative median length of stay (LOS), overall complication rates, major morbidity rates and 90-day mortality rates. Comparison between LLR for srHCC and LLR for nrHCC demonstrated no significant differences in baseline characteristics between both groups. There was also no significant difference in key perioperative outcomes such as median operating time, EBL, rate and volume of blood transfusion, median post-operative LOS, morbidity rates or mortality rates. CONCLUSION: LLR may be performed safely in selected cases of srHCC. These patients have comparable perioperative outcomes as those who undergo OLR for srHCC and LLR for nrHCC.

Impact of liver cirrhosis, severity of cirrhosis and portal hypertension on the difficulty of laparoscopic and robotic minor liver resections for primary liver malignancies in the anterolateral segments.

INTRODUCTION: We performed this study in order to investigate the impact of liver cirrhosis (LC) on the difficulty of minimally invasive liver resection (MILR), focusing on minor resections in anterolateral (AL) segments for primary liver malignancies. METHODS: This was an international multicenter retrospective study of 3675 patients who underwent MILR across 60 centers from 2004 to 2021. RESULTS: 1312 (35.7%) patients had no cirrhosis, 2118 (57.9%) had Child A cirrhosis and 245 (6.7%) had Child B cirrhosis. After propensity score matching (PSM), patients in Child A cirrhosis group had higher rates of open conversion (p = 0.024), blood loss >500 mls (p = 0.001), blood transfusion (p < 0.001), postoperative morbidity (p = 0.004), and in-hospital mortality (p = 0.041). After coarsened exact matching (CEM), Child A cirrhotic patients had higher open conversion rate (p = 0.05), greater median blood loss (p = 0.014) and increased postoperative morbidity (p = 0.001). Compared to Child A cirrhosis, Child B cirrhosis group had longer postoperative stay (p = 0.001) and greater major morbidity (p = 0.012) after PSM, and higher blood transfusion rates (p = 0.002), longer postoperative stay (p < 0.001), and greater major morbidity (p = 0.006) after CEM. After PSM, patients with portal hypertension experienced higher rates of blood loss >500 mls (p = 0.003) and intraoperative blood transfusion (p = 0.025). CONCLUSION: The presence and severity of LC affect and compound the difficulty of MILR for minor resections in the AL segments. These factors should be considered for inclusion into future difficulty scoring systems for MILR.

Laparoscopic versus open resection of hepatocellular carcinoma in patients with cirrhosis.

Hepatocellular carcinoma (HCC) is the sixth commonest malignancy worldwide, and the fourth-leading cause of cancer related death. Partial liver resection (LR) forms the mainstay of therapy for suitable patients with preserved liver function. In recent years, significant advances in surgical technology, refinement of operative techniques and improvements in peri-operative care have facilitated the widespread adoption of laparoscopic liver resection (LLR) with encouraging outcomes. Liver cirrhosis (LC) is present in up to 80% of patients with HCC, and adds a further dimension of complexity to LR. Cirrhotic patients have a propensity for greater intraoperative blood loss as well as increased postoperative complications such as refractory ascites and posthepatectomy liver failure. Tumor localization within the fibrotic parenchyma is challenging, giving rise to concerns about resection margin status. Patients are also at higher risk of developing metachronous lesions, which affects long-term survival. Presently, the exact role of LLR in HCC patients with underlying LC is not well-defined. Current evidence suggests that LLR offers a multitude of benefits in the short-term such as reduced blood loss and blood transfusion requirements and lower morbidity, when compared to open resection. Oncologic adequacy and long-term survival do not appear to be compromised. Special consideration must be given for LLR in patients with advanced cirrhosis, or those who require extensive major hepatectomies. We present here a brief review of the literature surrounding LLR for HCC on a background of LC.

Sub-classification of laparoscopic left hepatectomy based on hierarchic interaction of tumor location and size with perioperative outcomes.

BACKGROUND: The aim of this multicentric study was to investigate the impact of tumor location and size on the difficulty of Laparoscopic-Left Hepatectomy (L-LH). METHODS: Patients who underwent L-LH performed across 46 centers from 2004 to 2020 were analyzed. Of 1236 L-LH, 770 patients met the study criteria. Baseline clinical and surgical characteristics with a potential impact on LLR were included in a multi-label conditional interference tree. Tumor size cut-off was algorithmically determined. RESULTS: Patients were stratified into 3 groups based on tumor location and dimension: 457 in antero-lateral location (Group 1), 144 in postero-superior segment (4a) with tumor size ≤40 mm (Group 2), and 169 in postero-superior segment (4a) with tumor size >40 mm (Group 3). Patients in the Group 3 had higher conversion rate (7.0% vs. 7.6% vs. 13.0%, p-value .048), longer operating time (median, 240 min vs. 285 min vs. 286 min, p-value <.001), greater blood loss (median, 150 mL vs. 200 mL vs. 250 mL, p-value <.001) and higher intraoperative blood transfusion rate (5.7% vs. 5.6% vs. 11.3%, p-value .039). Pringle's maneuver was also utilized more frequently in Group 3 (66.7%), compared to Group 1 (53.2%) and Group 2 (51.8%) (p = .006). There were no significant differences in postoperative stay, major morbidity, and mortality between the three groups. CONCLUSION: L-LH for tumors that are >40 mm in diameter and located in PS Segment 4a are associated with the highest degree of technical difficulty. However, post-operative outcomes were not different from L-LH of smaller tumors located in PS segments, or tumors located in the antero-lateral segments.

Impact of tumor size on the difficulty of minimally invasive liver resection.

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<0.001, PGroup 3 vs 1<0.001, PGroup 3 vs 2<0.001), higher blood loss (PGroup 2 vs 1<0.001, PGroup 3 vs 1<0.001, PGroup 3 vs 2<0.001), as well as significantly longer hospital stay (PGroup 2 vs 1<0.001, PGroup 3 vs 1<0.001, PGroup 3 vs 2<0.001). There was a monotonic trend towards increasing blood transfusion rates (P = 0.006), overall morbidity (P = 0.029) and 90-day mortality rates (P = 0.047) with increasing tumour size. CONCLUSION: Although tumour size of 30 mm serves as an optimal cut-off for predicting difficult resections as per the Iwate criteria, a trichotomy (<30 mm, 30-69 mm, ≥70 mm) may provide additional granularity. Further large-scale prospective studies are needed to corroborate these findings.