Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Factors Associated with and Impact of Open Conversion in Laparoscopic and Robotic Minor Liver Resections: An International Multicenter Study of 10,541 Patients.

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

Impact of Tumor Size on the Difficulty of Laparoscopic Major Hepatectomies: An International Multicenter Study.

INTRODUCTION: Although tumor size (TS) is known to affect surgical outcomes in laparoscopic liver resection (LLR), its impact on laparoscopic major hepatectomy (L-MH) is not well studied. The objectives of this study were to investigate the impact of TS on the perioperative outcomes of L-MH and to elucidate the optimal TS cutoff for stratifying the difficulty of L-MH. METHODS: This was a post-hoc analysis of 3008 patients who underwent L-MH at 48 international centers. A total 1396 patients met study criteria and were included. The impact of TS cutoffs was investigated by stratifying TS at each 10-mm interval. The optimal cutoffs were determined taking into consideration the number of endpoints which showed a statistically significant split around the cut-points of interest and the magnitude of relative risk after correction for multiple risk factors. RESULTS: We identified 2 optimal TS cutoffs, 50 mm and 100 mm, which segregated L-MH into 3 groups. An increasing TS across these 3 groups (≤ 50 mm, 51-100 mm, > 100 mm), was significantly associated with a higher open conversion rate (11.2%, 14.7%, 23.0%, P < 0.001), longer operating time (median, 340 min, 346 min, 365 min, P = 0.025), increased blood loss (median, 300 ml,  ml, 400 ml, P = 0.002) and higher rate of intraoperative blood transfusion (13.1%, 15.9%, 27.6%, P < 0.001). Postoperative outcomes such as overall morbidity, major morbidity, and length of stay were comparable across the three groups. CONCLUSION: Increasing TS was associated with poorer intraoperative but not postoperative outcomes after L-MH. We determined 2 TS cutoffs (50 mm and 10 mm) which could optimally stratify the surgical difficulty of L-MH.

Risk Factors and Outcomes of Open Conversion During Minimally Invasive Major Hepatectomies: An International Multicenter Study on 3880 Procedures Comparing the Laparoscopic and Robotic Approaches.

INTRODUCTION: Despite the advances in minimally invasive (MI) liver surgery, most major hepatectomies (MHs) continue to be performed by open surgery. This study aimed to evaluate the risk factors and outcomes of open conversion during MI MH, including the impact of the type of approach (laparoscopic vs. robotic) on the occurrence and outcomes of conversions. METHODS: Data on 3880 MI conventional and technical (right anterior and posterior sectionectomies) MHs were retrospectively collected. Risk factors and perioperative outcomes of open conversion were analyzed. Multivariate analysis, propensity score matching, and inverse probability treatment weighting analysis were performed to control for confounding factors. RESULTS: Overall, 3211 laparoscopic MHs (LMHs) and 669 robotic MHs (RMHs) were included, of which 399 (10.28%) had an open conversion. Multivariate analyses demonstrated that male sex, laparoscopic approach, cirrhosis, previous abdominal surgery, concomitant other surgery, American Society of Anesthesiologists (ASA) score 3/4, larger tumor size, conventional MH, and Institut Mutualiste Montsouris classification III procedures were associated with an increased risk of conversion. After matching, patients requiring open conversion had poorer outcomes compared with non-converted cases, as evidenced by the increased operation time, blood transfusion rate, blood loss, hospital stay, postoperative morbidity/major morbidity and 30/90-day mortality. Although RMH showed a decreased risk of conversion compared with LMH, converted RMH showed increased blood loss, blood transfusion rate, postoperative major morbidity and 30/90-day mortality compared with converted LMH. CONCLUSIONS: Multiple risk factors are associated with conversion. Converted cases, especially those due to intraoperative bleeding, have unfavorable outcomes. Robotic assistance seemed to increase the feasibility of the MI approach, but converted robotic procedures showed inferior outcomes compared with converted laparoscopic procedures.

Minimally Invasive Versus Open Liver Resections for Hepatocellular Carcinoma in Patients With Metabolic Syndrome.

OBJECTIVE: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). BACKGROUND: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. MATERIAL AND METHODS: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. RESULTS: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival. CONCLUSIONS: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.