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Browsing by Author "Ratti, F"

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  • An Attempt to Establish and Apply Global Benchmarks for Liver Resection of Malignant Hepatic Tumors
    Publication . 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, T
    Background: 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.
    2023-12Journal article Open access Show more
  • Application of Hazard Functions to Investigate Recurrence After Curative-Intent Resection for Hepatocellular Carcinoma
    Publication . 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, T
    Background: 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.
    2023-02Journal article Open access Show more
  • Early Versus Late Recurrence of Hepatocellular Carcinoma After Surgical Resection Based on Post-Recurrence Survival: an International Multi-Institutional Analysis
    Publication . 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, T
    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.
    2021Journal article Open access Show more
  • Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: an International Multi-Institutional Analysis
    Publication . 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, T
    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 (> 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.
    2020Journal article Open access Show more
  • Evaluation of the ACS NSQIP Surgical Risk Calculator in Elderly Patients Undergoing Hepatectomy for Hepatocellular Carcinoma
    Publication . 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, T
    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.
    2020Journal article Open access Show more
  • Hepatocellular Carcinoma Tumour Burden Score to Stratify Prognosis After Resection
    Publication . 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, T
    Background: 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.
    2020-06Journal article Open access Show more
  • Hospital Variation in Textbook Outcomes Following Curative-Intent Resection of Hepatocellular Carcinoma: an International Multi-Institutional Analysis
    Publication . Tsilimigras, D; Mehta, R; Merath, K; Bagante, F; Paredes, AZ; Farooq, A; 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; Aldrighetti, L; Endo, I; Pawlik, T
    Background: Composite measures such as "Textbook Outcome" (TO) may be superior to individual quality metrics to assess surgical care and hospital performance. However, the incidence and factors associated with TO after resection of HCC remain poorly defined. Methods: Hospital variation in the rates of TO, factors associated with achieving a TO and the impact of TO on long-term survival following resection for HCC were examined using an international multi-institutional database. Results: Among 605 patients who underwent curative-intent resection of HCC, the unadjusted incidence of TO ranged from 50.9% to 77.7%. While achievement of each individual quality metric was relatively high (range, 74.5-98.0%), an overall TO was achieved among only 62.3% (n = 377) of patients. At the hospital level, TO ranged from 54.3% to 72.9%. Patients with BCLC-0 HCC (referent BCLC-B/C; OR: 4.17, 95%CI: 1.62-10.7) and ALBI grade 1 (referent ALBI grade 2/3; OR: 1.49, 95%CI: 1.06-2.11) had higher odds of achieving a TO. On multivariable analysis, TO was associated with improved overall survival (HR: 0.60, 95% CI: 0.42-0.85). Conclusion: Roughly 6 in 10 patients achieved a TO following resection for HCC. When achieved, TO was associated with better long-term outcomes. TO is a simple composite measure of both short- and long-term outcomes among patients undergoing resection for HCC.
    2020-09Journal article Open access Show more
  • Impact of Time‐to‐Surgery on Outcomes of Patients Undergoing Curative‐Intent Liver Resection for BCLC‐0, A and B Hepatocellular Carcinoma
    Publication . Tsilimigras, DI; Hyer, JM; Diaz, A; Moris, D; Bagante, F; Ratti, F; Pinto Marques, H; Soubrane, O; Lam, V; Poultsides, GA; Popescu, I; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Pawlik, TM
    Background: The impact of a prolonged time-to-surgery (TTS) among patients with resectable hepatocellular carcinoma (HCC) is not well defined. Methods: Patients who underwent curative-intent hepatectomy for BCLC-0, A and B HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of prolonged TTS on overall survival (OS) and disease-free survival (DFS) was examined. Results: Among 775 patients who underwent resection for HCC, 537 (69.3%) had early surgery (TTS < 90 days) and 238 (30.7%) patients had a delayed surgery (TTS ≥ 90 days). Patient- and tumor-related characteristics were similar between the two groups except for a higher proportion of patients undergoing major liver resection in the early surgery group (31.3% vs. 23.8%, p = .04). The percentage of patients with delayed surgery varied from 8.8% to 59.1% among different centers (p < .001). Patients with TTS < 90 days had similar 5-year OS (63.7% vs. 64.9; p = .79) and 5-year DFS (33.5% vs. 42.4; p = .20) with that of patients with TTS ≥ 90 days. On multivariable analysis, delayed surgery was not associated with neither worse OS (BCLC-0/A: adjusted hazards ratio [aHR] = 0.90; 95% confidence interval [CI]: 0.65-1.25 and BCLC-B: aHR = 0.72; 95%CI: 0.30-1.74) nor DFS (BCLC-0/A: aHR = 0.78; 95%CI: 0.60-1.01 and BCLC-B: aHR = 0.67; 95% CI: 0.36-1.25). Conclusion: Approximately one in three patients diagnosed with resectable HCC had a prolonged TTS. Delayed surgery was not associated with worse outcomes among patients with resectable HCC.
    2021Journal article Open access Show more
  • Impact of Tumor Burden Score on Conditional Survival after Curative-Intent Resection for Hepatocellular Carcinoma: A Multi-Institutional Analysis
    Publication . Elfadaly, AN; Tsilimigras, DI; Hyer, JM; Paro, A; Bagante, F; Ratti, F; Marques, HP; Soubrane, O; Lam, V; Poultsides, GA; Popescu, I; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Pawlik, TM
    Background: The impact of tumor burden score (TBS) on conditional survival (CS) among patients undergoing curative-intent resection of hepatocellular carcinoma (HCC) has not been examined to date. Methods: Patients who underwent liver resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS and other clinicopathologic factors on 3-year conditional survival (CS3) was examined. Results: Among 1,040 patients, 263 (25.3%) patients had low TBS, 668 (64.2%) had medium TBS and 109 (10.5%) had high TBS. TBS was strongly associated with OS; 5-year OS was 39.0% among patients with high TBS compared with 61.1% and 79.4% among patients with medium and low TBS, respectively (p < 0.001). While actuarial survival decreased as time elapsed from resection, CS increased over time irrespective of TBS. The largest differences between 3-year actuarial survival and CS3 were noted among patients with high TBS (5-years postoperatively; CS3: 78.7% vs. 3-year actuarial survival: 30.7%). The effect of adverse clinicopathologic factors including high TBS, poor/undifferentiated tumor grade, microvascular invasion, liver capsule involvement, and positive margins on prognosis decreased over time. Conclusions: CS rates among patients who underwent resection for HCC increased as patients survived additional years, irrespective of TBS. CS estimates can be used to provide important dynamic information relative to the changing survival probability after resection of HCC.
    2021Journal article Open access Show more
  • Long-Term Outcomes After Curative Resection of HCV-Positive Versus Non-Hepatitis Related Hepatocellular Carcinoma: an International Multi-Institutional Analysis
    Publication . Wei, T; Zhang, XF; Bagante, F; Ratti, F; Pinto Marques, H; Soubrane, O; Lam, V; Poultsides, G; Popescu, I; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Aldrighetti, L; Pawlik, T
    Background: To define the chronological changes of long-term survival among patients with non-hepatitis-related hepatocellular carcinoma (Non-Hep-HCC) versus hepatitis C-related HCC (HCV-HCC) over the last two decades. Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Overall (OS) and recurrence-free survival (RFS) were analyzed and compared among Non-Hep-HCC versus HCV-HCC patients. Propensity score matching (PSM) was utilized to mitigate residual bias. Results: Among 617 patients, 196 (31.8%) patients had HCV-HCC, whereas 421 (68.2%) patients had Non-Hep-HCC. While patients with HCV-HCC had an improvement in OS over time (5-year OS, 2000-2009 55% vs. 2010-2017 67%, p = 0.034), OS among patients with Non-Hep-HCC remain unchanged (5-year OS, 2000-2009 53% vs. 2010-2017 52%, p = 0.905). In the matched cohort, patients with HCV-HCC had a worse OS versus patients with Non-Hep-HCC during 2000 and 2009 (5-year OS, 12% vs. 63%, p = 0.029), but significantly better OS from 2010 to 2017 than patients with Non-Hep-HCC (5-year OS, 86% vs. 73%, p = 0.035). The recurrence timing, patterns and re-treatments were comparable among Non-Hep-HCC and HCV-HCC patients. Conclusion: While OS of patients with HCV-HCC improved over time, the long-term survival of patients with Non-Hep-HCC patients remained unchanged and was more unfavorable.
    2020Journal article Open access Show more