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Background: To define early versus late recurrence based on post-recurrence survival (PRS) among patients undergoing curative resection for hepatocellular carcinoma (HCC). Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The optimal cut-off time point to discriminate early versus late recurrence was determined relative to PRS. Results: Among 1004 patients, 443 (44.1%) patients experienced recurrence with a median recurrence-free survival time of 12 months. A cut-off time point of 8 months was defined as the optimal threshold based on sensitivity analyses relative to PRS for early (n = 165, 37.2%) versus late relapse (n = 278, 62.8%) (p = 0.008). Early recurrence was associated with worse PRS (median PRS, 27.0 vs. 43.0 months, p = 0.019), as well as overall survival (OS) (median OS, 32.0 versus 74.0 months, p < 0.001) versus late recurrence. In addition, patients who recurred early were more likely to recur at extra- ± intrahepatic (35.5% vs. 19.8%, p = 0.003) sites and were less likely to have the recurrence treated with curative intent (33.8% vs. 45.7%, p = 0.08). Patients undergoing curative re-treatment of late recurrence had a comparable OS with patients who had no recurrence (median OS, 139.0 vs. 140.0 months); patients with early recurrence had inferior OS after curative re-treatment versus patients with no recurrence (median OS, 69.0 vs. 140.0 months, p = 0.036), yet still better than patients who received palliative treatment for early recurrence (median OS, 69.0 vs. 21.0 months, p < 0.001). Conclusions: Eight months was identified as the cut-off value to differentiate early versus late recurrence. Curative-intent treatment for recurrent intrahepatic tumors was associated with reasonable long-term outcomes. info:eu-repo/semantics/publishedVersion

Introduction: Although a positive surgical margin is a known prognostic factor for recurrence, the optimal surgical margin width in the context of an R0 resection for early-stage hepatocellular carcinoma (HCC) is still debated. The aim of the current study was to examine the impact of wide (> 1cm) versus narrow (< 1cm) surgical margin status on the incidence and recurrence patterns among patients with T1 HCC undergoing an R0 hepatectomy. Methods: Between 1998 and 2017, patients with T1 HCC who underwent R0 hepatectomy for stage T1 HCC were identified using an international multi-institutional database. Recurrence-free survival (RFS) was estimated, and recurrence patterns were examined based on whether patients had a wide versus narrow resection margins. Results: Among 404 patients, median patient age was 66years (IQR: 58–73). Most patients (n = 326, 80.7%) had surgical margin < 1cm, while 78 (19.3%) patients had a >1cm margin. The majority of patients had early recurrences (< 24months) in both margin width groups (< 1cm: 70.3% vs > 1cm: 85.7%, p = 0.141); recurrence site was mostly intrahepatic (< 1cm: 77% vs > 1cm: 61.9%, p = 0.169). The 1-, 3-, and 5-year RFS among patients with margin < 1cm were 77%, 48.9%, and 35.3% versus 81.7%, 65.8%, and 60.7% for patients with margin > 1cm, respectively (p = 0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: < 1cm: 49.2% vs > 1cm: 58.9%, p = 0.169), whereas in the non-anatomic resection group, margin width >1cm was associated with a better 3-year RFS compared to margin < 1cm (86.7% vs 47.3%, p = 0.017). On multivariable analysis, margin > 1cm remained protective against recurrence (HR = 0.50, 95%CI 0.28–0.89), whereas Child-Pugh B (HR = 2.13, 95%CI 1.09–4.15), AFP > 20 ng/mL (HR = 1.71, 95%CI 1.18–2.48), and presence of microscopic lymphovascular invasion (HR = 1.48, 95%CI 1.01–2.18) were associated with a higher hazard of recurrence. Conclusion: Resection margins > 1cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (< 5cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.

Background: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator (SRC) aims to help predict patient-specific risk for morbidity and mortality. The performance of the SRC among an elderly population undergoing curative-intent hepatectomy for hepatocellular carcinoma (HCC) remains unknown. Methods: Patients > 70 years of age who underwent hepatectomy for HCC between 1998 and 2017 were identified using a multi-institutional international database. To estimate the performance of SRC, 12 observed postoperative outcomes were compared with median SRC-predicted risk, and C-statistics and Brier scores were calculated. Results: Among 500 patients, median age was 75 years (IQR 72-78). Most patients (n = 324, 64.8%) underwent a minor hepatectomy, while 35.2% underwent a major hepatectomy. The observed incidence of venous thromboembolism (VTE) (3.2%) and renal failure (RF) (4.4%) exceeded the median predicted risk (VTE, 1.8%; IQR 1.5-3.1 and RF, 1.0%; IQR 0.5-2.0). In contrast, the observed incidence of 30-day readmission (7.0%) and non-home discharge (2.5%) was lower than median-predicted risk (30-day readmission, 9.4%; IQR 7.4-12.8 and non-home discharge, 5.7%; IQR 3.3-11.7). Only 57.8% and 71.2% of patients who experienced readmission (C-statistic, 0.578; 95%CI 0.468-0.688) or mortality (C-statistic, 0.712; 95%CI 0.508-0.917) were correctly identified by the model. Conclusion: Among elderly patients undergoing hepatectomy for HCC, the SRC underestimated the risk of complications such as VTE and RF, while being no better than chance in estimating the risk of readmission. The ACS SRC has limited clinical applicability in estimating perioperative risk among elderly patients being considered for hepatic resection of HCC. info:eu-repo/semantics/publishedVersion

Introduction: Patients with intrahepatic cholangiocarcinoma (ICC) generally have a poor prognosis, yet there can be heterogeneity in thepatterns of presentation and associated outcomes. We sought to identify clusters of ICC patients based on preoperative characteristics that may have distinct outcomes based on differing patterns of presentation. Methods: Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified using a multi-institutional database. A cluster analysis was performed based on preoperative variables to identify distinct patterns of presentation. A classification tree was built to prospectively assign patients into cluster assignments. Results: Among 826 patients with ICC, three distinct presentation patterns were noted. Specifically, Cluster 1 (common ICC, 58.9%) consisted of individuals who had a small-size ICC (median 4.6cm) and median carbohydrate antigen (CA)19-9 and neutrophil-to-lymphocyte ratio (NLR) levels of 40.3UI/mL and 2.6, respectively; Cluster 2 (proliferative ICC, 34.9%) consisted of patients who had larger-size tumors (median 9.0cm), higher CA19-9 levels (median 72.0UI/mL), and similar NLR (median 2.7); Cluster 3 (inflammatory ICC, 6.2%) comprised of patients with a medium-size ICC (median 6.2cm), the lowest range of CA19-9 (median 26.2UI/mL), yet the highest NLR (median 13.5) (all p < 0.05). Median OS worsened incrementally among the three different clusters {Cluster 1 vs. 2 vs. 3; 60.4months (95% confidence interval [CI] 43.0–77.8) vs. 27.2months (95% CI 19.9–34.4) vs. 13.3months (95% CI 7.2–19.3); p < 0.001}. The classification tree used to assign patients into different clusters had an excellent agreement with actual cluster assignment (κ = 0.93, 95% CI 0.90–0.96). Conclusion: Machine learning analysis identified three distinct prognostic clusters based solely on preoperative characteristics among patients with ICC. Characterizing preoperative patient heterogeneity with machine learning tools can help physicians with preoperative selection and risk stratification of patients with ICC.

Background: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have questioned the prognostic stratification of this classification schema, as well as the proposed treatment allocation of patients with a single large tumor. Methods: Patients who underwent curative-intent hepatectomy for histologically proven hepatocellular carcinoma (HCC) between 1998 and 2017 were identified using an international multi-institutional database. Overall survival (OS) among patients with BCLC stage 0, A, and B was examined. Patients with a single large tumor were classified as BCLC stage A1 and were independently assessed. Results: Among 814 patients, 68 (8.4%) were BCLC-0, 310 (38.1%) were BCLC-A, 279 (34.3%) were BCLC-A1, and 157 (19.3%) were BCLC-B. Five-year OS among patients with BCLC stage 0, A, A1, and B HCC was 86.2%, 69.0%, 56.9%, and 49.9%, respectively (p < 0.001). Among patients with very early- and early-stage HCC (BCLC 0, A, and A1), patients with BCLC stage A1 had the worst OS (p = 0.0016). No difference in survival was noted among patients undergoing surgery for BCLC stage A1 and B HCC (5-year OS: 56.9% vs. 49.9%; p = 0.259) even after adjusting for competing factors (hazard ratio 0.83, 95% confidence interval 0.54-1.28; p = 0.40). Conclusion: Prognosis following liver resection among patients with BCLC-A1 HCC was similar to patients presenting with BCLC-B tumors. Surgery provided acceptable long-term outcomes among select patients with BCLC-B HCC. Designation into BCLC stage B should not be considered an a priori contraindication to surgery. info:eu-repo/semantics/publishedVersion