Browsing by Author "Alexandrescu, S"
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- An Attempt to Establish and Apply Global Benchmarks for Liver Resection of Malignant Hepatic TumorsPublication . Alaimo, L; Moazzam, Z; Lima, H; Endo, Y; Ruzzenente, A; Guglielmi, A; Ratti, F; Aldrighetti, L; Weiss, M; Bauer, T; Alexandrescu, S; Popescu, I; Poultsides, G; Maithel, S; Pinto Marques, H; Martel, G; Pulitano, C; Shen, F; Cauchy, F; Koerkamp, B; Endo, I; Kitago, M; Aucejo, F; Sasaki, K; Fields, R.; Hugh, T; Lam, V; Pawlik, TBackground: Benchmarking is a process of continuous self-evaluation and comparison with best-in-class hospitals to guide quality improvement initiatives. We sought to define global benchmarks relative to liver resection for malignancy and to assess their achievement in hospitals in the United States. Methods: Patients who underwent curative-intent liver resection for hepatocellular carcinoma, intrahepatic cholangiocarcinoma, or colorectal or neuroendocrine liver metastases between 2000 and 2019 were identified from an international multi-institutional database. Propensity score matching was conducted to balance baseline characteristics between open and minimally invasive approaches. Best-in-class hospitals were defined relative to the achievement rate of textbook oncologic outcomes and case volume. Benchmark values were established relative to best-in-class institutions. The achievement of benchmark values among hospitals in the National Cancer Database was then assessed. Results: Among 2,624 patients treated at 20 centers, a majority underwent liver resection for hepatocellular carcinoma (n = 1,609, 61.3%), followed by colorectal liver metastases (n = 650, 24.8%), intrahepatic cholangiocarcinoma (n = 299, 11.4%), and neuroendocrine liver metastases (n = 66, 2.5%). Notably, 1,947 (74.2%) patients achieved a textbook oncologic outcome. After propensity score matching, 6 best-in-class hospitals with the highest textbook oncologic outcome rates (≥75.0%) were identified. Benchmark values were calculated for margin positivity (≤11.7%), 30-day readmission (≤4.1%), 30-day mortality (≤1.6%), minor postoperative complications (≤24.7%), severe complications (≤12.4%), and failure to achieve the textbook oncologic outcome (≤22.8%). Among the National Cancer Database hospitals, global benchmarks for margin positivity, 30-day readmission, 30-day mortality, severe complications, and textbook oncologic outcome failure were achieved in 62.9%, 27.1%, 12.1%, 7.1%, and 29.3% of centers, respectively. Conclusion: These global benchmarks may help identify hospitals that may benefit from quality improvement initiatives, aiming to improve patient safety and surgical oncologic outcomes.
- Application of Hazard Functions to Investigate Recurrence After Curative-Intent Resection for Hepatocellular CarcinomaPublication . Lima, H; Alaimo, L; Brown, Z; Endo, Y; Moazzam, Z; Tsilimigras, D; Shaikh, C; Resende, V; Guglielmi, A; Ratti, F; Aldrighetti, L; Pinto Marques, H; Soubrane, O; Lam, V; Poultsides, G; Popescu, I; Alexandrescu, S; Martel, G; Hugh, T; Endo, I; Shen, F; Pawlik, TBackground: Defining patterns and risk of recurrence can help inform surveillance strategies and patient counselling. We sought to characterize peak hazard rates (pHR) and peak time of recurrence among patients who underwent resection of hepatocellular carcinoma (HCC). Methods: 1434 patients who underwent curative-intent resection of HCC were identified from a multi-institutional database. Hazard, patterns, and peak rates of recurrence were characterized. Results: The overall hazard of recurrence peaked at 2.4 months (pHR: 0.0384), yet varied markedly. The incidence of recurrence increased with Barcelona Clinic Liver Cancer (BCLC) stage 0 (29%), A (54%), and B (64%). While the hazard function curve for BCLC 0 patients was relatively flat (pHR: <0.0177), BCLC A patients recurred with a peak at 2.4 months (pHR: 0.0365). Patients with BCLC B had a bimodal recurrence with a peak rate at 4.2 months (pHR: 0.0565) and another at 22.8 months. The incidence of recurrence also varied according to AFP level (≤400 ng/mL: 52.6% vs. >400 ng/mL: 36.3%) and Tumor Burden Score (low: 73.7% vs. medium: 50.6% vs. high: 24.2%) (both p < 0.001). Conclusion: Recurrence hazard rates for HCC varied substantially relative to both time and intensity/peak rates. TBS and AFP markedly impacted patterns of hazard risk of recurrence.
- Assessment of the Lymph Node Status in Patients Undergoing Liver Resection for Intrahepatic Cholangiocarcinoma: the New Eighth Edition AJCC Staging SystemPublication . Bagante, F; Spolverato, G; Weiss, M; Alexandrescu, S; Pinto Marques, H; Aldrighetti, L; Maithel, SK; Pulitano, C; Bauer, TW; Shen, F; Poultsides, GA; Soubrane, O; Martel, G; Groot Koerkamp, B; Guglielmi, A; Itaru, E; Pawlik, TMINTRODUCTION: The role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus <6 HLNs. MATERIALS AND METHODS: Patients undergoing hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary centers were identified. RESULTS: Among 1154 patients undergoing hepatectomy for ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN). Among NLN patients, HLN was associated with 5-year OS (p = 0.098). While HLN did not impact 5-year OS among MLN patients (p = 0.71), the number of MLN was associated with 5-year OS (p = 0.02). Among the 317 (27.5%) patients staged according the AJCC eighth edition staging system, N1 patients had a 3-fold increased risk of death compared with N0 patients (hazard ratio 3.03; p < 0.001). CONCLUSION: Only one fourth of patients undergoing hepatectomy for ICC had adequate nodal staging according to the AJCC eighth edition. While the six HLN cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN was associated with long-term survival of N1 patients.
- Comparative Performances of the 7th and the 8th Editions of the American Joint Committee on Cancer Staging Systems for Intrahepatic CholangiocarcinomaPublication . Spolverato, G; Bagante, F; Weiss, M; Alexandrescu, S; Pinto Marques, H; Aldrighetti, L; Maithel, SK; Pulitano, C; Bauer, TW; Shen, F; Poultsides, GA; Soubrane, O; Martel, G; Koerkamp, BG; Guglielmi, A; Itaru, E; Pawlik, TMBACKGROUND: We sought to evaluate and validate the 8th edition of the AJCC classification using a multi-institutional cohort of patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Patients undergoing curative-intent hepatic resection for ICC between 1990 and 2015 at 14 major hepatobiliary centers were included and were staged according to 7th and 8th editions AJCC criteria. RESULTS: A total of 1154 patients underwent liver resection for ICC. When patients were staged using the AJCC 7th edition, T2a, T2b, and T4 patients had a higher hazard ratio (HR) of death compared with T1 (T2a, HR 1.43, P = 0.004; T2b, HR 1.99, P < 0.001; T4, HR 2.20, P < 0.001). T3 patients had a higher HR of death compared with T1 patients (HR 1.30, P = 0.029) but lower than T2a and T2b. According to AJCC 8th edition, T1b, T2, and T4 patients were at higher risk of death compared with T1a patients (T1b, HR 1.91, P < 0.001; T2, HR 2.29, P < 0.001; T4, HR 4.16, P < 0.001). As in the AJCC 7th edition, AJCC 8th edition T3 patients had a higher HR of death compared with T1 patients (HR 1.65, P = 0.001) but lower than T1b and T2. AJCC 8th edition. T-category performed slightly better than AJCC 7th edition with a C-index of 0.609 versus 0.590. CONCLUSIONS: A staging system that perfectly discriminates between stages has not yet been developed, but the AJCC 8th edition was able to better stratify the risk of death of Stage III and T3 patients.
- Complications After Liver Surgery: a Benchmark AnalysisPublication . Bagante, F; Ruzzenente, A; Beal, E; Campagnaro, T; Merath, K; Conci, S; Akgül, O; Alexandrescu, S; Pinto Marques, H; Lam, V; Shen, F; Poultsides, G; Soubrane, O; Martel, G; Iacono, C; Guglielmi, A; Pawlik, TBackground: The best achievable short-term outcomes after liver surgery have not been identified. Several factors may influence the post-operative course of patients undergoing hepatectomy increasing the risk of post-operative complications. We sought to identify risk-adjusted benchmark values [BMV] for liver surgery. Methods: The National Surgery Quality Improvement Program (NSQIP) database was used to develop Bayesian models to estimate risk-adjusted BMVs for overall and liver related (post-hepatectomy liver failure [PHLF], biliary leakage [BL]) complications. A separate international multi-institutional database was used to validate the risk-adjusted BMVs. Results: Among the 11,243 patients included in the NSQIP database, the incidence of complications, PHLF, and BL was 36%, 5%, and 8%, respectively. The risk-adjusted BMVs for complication (range, 16-72%), PHLF (range, 1%-20%), and BL (range, 4%-22%) demonstrated a high variability based on patients characteristics. When tested using an international database including nine institutes, the risk-adjusted BMVs for complications ranged from 26% (Institute-4) to 43% (Institute-1), BMVs for PHLF between 3% (Institute-3) and 12% (Institute-5), while BMVs for BL ranged between 5% (Institute-4) and 9% (Institute-7). Conclusions: Multiple factors influence the risk of complications following hepatectomy. Risk-adjusted BMVs are likely much more applicable and appropriate in assessing "acceptable" benchmark outcomes following liver surgery.
- Defining Long-Term Survivors Following Resection of Intrahepatic CholangiocarcinomaPublication . Bagante, F; Spolverato, G; Weiss, M; Alexandrescu, S; Pinto Marques, H; Aldrighetti, L; Maithel, SK; Pulitano, C; Bauer, TW; Shen, F; Poultsides, GA; Soubrane, O; Martel, G; Groot Koerkamp, B; Guglielmi, A; Itaru, E; Pawlik, TMBACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival. METHODS: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5). RESULTS: Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived < 5 years, as well as patients were alive yet had < 5 years of follow-up, 153 patients (22.5%) who survived ≥ 5 years were included in the LT group, while 526 patients (77.5%) who died < 5 years from the date of surgery were included in the non-LT group. Factors associated with not surviving to 5 years included perineural invasion (OR 4.78, 95% CI, 1.92-11.8; p = 0.001), intrahepatic metastasis (OR 3.75, 95% CI, 0.85-16.6, p = 0.082), satellite lesions (OR 2.12, 95% CI, 1.15-3.90, p = 0.016), N1 status (OR 4.64, 95% CI, 1.77-12.2; p = 0.002), ICC > 5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT. CONCLUSION: While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term.
- Early Versus Late Recurrence of Hepatocellular Carcinoma After Surgical Resection Based on Post-Recurrence Survival: an International Multi-Institutional AnalysisPublication . Wei, T; Zhang, XF; Bagante, F; Ratti, F; Pinto Marques, H; Silva, S; Soubrane, O; Lam, V; Poultsides, G; Popescu, I; Grigorie, R; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Lv, Y; Aldrighetti, L; Pawlik, TBackground: 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.
- Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: an International Multi-Institutional AnalysisPublication . Tsilimigras, D; Sahara, K; Moris, D; Hyer, J; Paredes, A; Bagante, F; Merath, K; Farooq, A; Ratti, F; Pinto Marques, H; Soubrane, O; Azoulay, D; Lam, V; Poultsides, G; Popescu, I; Alexandrescu, S; Martel, G; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Pawlik, TIntroduction: 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 (> 1 cm) versus narrow (< 1 cm) 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 66 years (IQR: 58-73). Most patients (n = 326, 80.7%) had surgical margin < 1 cm, while 78 (19.3%) patients had a > 1 cm margin. The majority of patients had early recurrences (< 24 months) in both margin width groups (< 1 cm: 70.3% vs > 1 cm: 85.7%, p = 0.141); recurrence site was mostly intrahepatic (< 1 cm: 77% vs > 1 cm: 61.9%, p = 0.169). The 1-, 3-, and 5-year RFS among patients with margin < 1 cm were 77%, 48.9%, and 35.3% versus 81.7%, 65.8%, and 60.7% for patients with margin > 1 cm, respectively (p = 0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: < 1 cm: 49.2% vs > 1 cm: 58.9%, p = 0.169), whereas in the non-anatomic resection group, margin width > 1 cm was associated with a better 3-year RFS compared to margin < 1 cm (86.7% vs 47.3%, p = 0.017). On multivariable analysis, margin > 1 cm 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 > 1 cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (< 5 cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.
- Evaluation of the ACS NSQIP Surgical Risk Calculator in Elderly Patients Undergoing Hepatectomy for Hepatocellular CarcinomaPublication . Sahara, K; Paredes, A; Merath, K; Tsilimigras, D; Bagante, F; Ratti, F; Pinto Marques, H; Soubrane, O; Beal, E; Lam, V; Poultsides, G; Popescu, I; Alexandrescu, S; Martel, G; Aklile, W; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Pawlik, TBackground: 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.
- Hepatocellular Carcinoma Tumour Burden Score to Stratify Prognosis After ResectionPublication . Tsilimigras, D; Moris, D; Hyer, J; Bagante, F; Sahara, K; Moro, A; Paredes, A; Mehta, R; Ratti, F; Pinto Marques, H; Silva, S; Soubrane, O; Lam, V; Poultsides, G; Popescu, I; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Sasaki, K; Rodarte, A; Aucejo, F; Pawlik, TBackground: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. Methods: Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. Results: Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010). Conclusion: The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.