Browsing by Author "Weiss, M"
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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.
- Antibodies Towards High-Density Lipoprotein Components in Patients with PsoriasisPublication . Hu, LS; Zhang, XF; Weiss, M; Popescu, I; Pinto Marques, H; Delgado Alves, L; Maithel, S; Pulitano, C; Bauer, T; Shen, F; Poultsides, G; Soubrane, O; Martel, G; Koerkamp, B; Itaru, E; Lv, Y; Pawlik, TObjectives: To assess conditional survival (CS) according to recurrence status, as well as conditional disease-free survival (cDFS) among patients with intrahepatic cholangiocarcinoma (ICC). Methods: CS and cDFS were evaluated among ICC patients who underwent curative-intent resection for ICC by using a multi-institutional database. Five-year CS (CS5) at "x" years was calculated separately for patients who did and did not experience recurrence. The cDFS3 at "x" years was defined as the chance to be disease-free for an additional 3 years after not having experienced a recurrence for "x" years postoperatively. Results: Among 1221 patients, median OS was 36.8 months. While estimated actuarial OS decreased over time, CS5 increased as patients survived over longer periods of time and reached 93.9% at 4 years among 139 patients who did not experience a recurrence. Among the 725 (59.4%) patients who did experience a tumor recurrence, CS5 decreased to 17.7% the first postoperative year; however, CS5 subsequently increased to 79.7% for 81 patients who had survived 4 years after surgery. While actuarial DFS decreased from 54.6% at 1 year to 28.2% at 5 years, estimated cDFS3 following liver resection increased over time. Of note, patients with known risk factors for recurrence had even more marked improvements in cDFS3 over subsequent years versus patients without risk factors for recurrence. Conclusion: CS and cDFS changed over time according to the presence of disease-specific risk factors, as well as the presence 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.
- Classification of Intrahepatic Cholangiocarcinoma into Perihilar Versus Peripheral SubtypePublication . Wei, T; Lu, J; Xiao, XL; Weiss, M; Popescu, I; Pinto Marques, H; Aldrighetti, L; Maithel, SK; Pulitano, C; Bauer, TW; Shen, F; Poultsides, GA; Soubrane, O; Martel, G; Koerkamp, BG; Itaru, E; Lv, Y; Zhang, XF; Pawlik, TMBackground: Intrahepatic cholangiocarcinoma (ICC) constitutes a group of heterogeneous malignancies within the liver. We sought to subtype ICC based on anatomical origin of tumors, as well as propose modifications of the current classification system. Methods: Patients undergoing curative-intent resection for ICC, hilar cholangiocarcinoma (CCA), or hepatocellular carcinoma (HCC) were identified from three international multi-institutional consortia of databases. Clinicopathological characteristics and survival outcomes were assessed. Results: Among 1264 patients with ICC, 1066 (84.3%) were classified as ICC-peripheral subtype, whereas 198 (15.7%) were categorized as ICC-perihilar subtype. Compared with ICC-peripheral subtype, ICC-perihilar subtype was more often associated with aggressive tumor characteristics, including a higher incidence of nodal metastasis, macro- and microvascular invasion, perineural invasion, as well as worse overall survival (OS) (median: ICC-perihilar 19.8 vs. ICC-peripheral 37.1 months; p < 0.001) and disease-free survival (DFS) (median: ICC-perihilar 12.8 vs. ICC-peripheral 15.2 months; p = 0.019). ICC-perihilar subtype and hilar CCA had comparable OS (19.8 vs. 21.4 months; p = 0.581) and DFS (12.8 vs. 16.8 months; p = 0.140). ICC-peripheral subtype tumors were associated with more advanced tumor features, as well as worse survival outcomes versus HCC (OS, median: ICC-peripheral 37.1 vs. HCC 74.3 months; p < 0.001; DFS, median: ICC-peripheral 15.2 vs. HCC 45.5 months; p < 0.001). Conclusions: ICC should be classified as ICC-perihilar and ICC-peripheral subtype based on distinct clinicopathological features and survival outcomes. ICC-perihilar subtype behaved more like carcinoma of the bile duct (i.e., hilar CCA), whereas ICC-peripheral subtype had features and a prognosis more akin to a primary liver malignancy.
- 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.
- 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 Recurrence of Neuroendocrine Liver Metastasis After Curative Hepatectomy: Risk Factors, Prognosis, and TreatmentPublication . Zhang, XF; Beal, EW; Chakedis, J; Lv, Y; Bagante, F; Aldrighetti, L; Poultsides, GA; Bauer, TW; Fields, RC; Maithel, SK; Pinto Marques, H; Weiss, M; Pawlik, TBACKGROUND: Early tumor recurrence after curative resection typically indicates a poor prognosis. The objective of the current study was to investigate the risk factors, treatment, and prognosis of early recurrence of neuroendocrine tumor (NET) liver metastasis (NELM) after hepatic resection. METHODS: A total of 481 patients who underwent curative-intent resection for NELM were identified from a multi-institutional database. Data on clinicopathological characteristics, intraoperative details, and outcomes were documented. The optimal cutoff value to differentiate early and late recurrence was determined to be 3 years based on linear regression. RESULTS: With a median follow-up of 60 months, 223 (46.4%) patients developed a recurrence, including 158 (70.9%) early and 65 (29.1%) late recurrences. On multivariable analysis, pancreatic NET, primary tumor lymph node metastasis, and a microscopic positive surgical margin were independent risk factors for early intrahepatic recurrence. While recurrence patterns and treatments were comparable among patients with early and late recurrences, early recurrence was associated with worse disease-specific survival than late recurrences (10-year NELM-specific survival, 44.5 vs 75.8%, p < 0.001). Among the 34 (21.5%) patients who underwent curative treatment for early recurrence, post-recurrence disease-specific survival was better than non-curatively treated patients (10-year NELM-specific survival, 54.2 vs 26.3%, p = 0.028), yet similar to patients with late recurrences treated with curative intent (10-year NELM-specific survival, 54.2 vs 37.4%, p = 0.519). CONCLUSIONS: Early recurrence after surgery for NELM was associated with the pancreatic type, primary lymph node metastasis, and extrahepatic disease. Re-treatment with curative intent prolonged survival after recurrence, and therefore, operative intervention even for early recurrences of NELM should be considered.
- Early Versus Late Recurrence of Intrahepatic Cholangiocarcinoma After Resection With Curative IntentPublication . Zhang, XF; Beal, EW; Bagante, F; Chakedis, J; Weiss, M; Popescu, I; Pinto Marques, H; Aldrighetti, L; Maithel, SK; Pulitano, C; Bauer, TW; Shen, F; Poultsides, GA; Soubrane, O; Martel, G; Koerkamp, BG; Itaru, E; Pawlik, TMBackground: The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. Methods: Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. Results: A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). Conclusion: Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.
- Hepatic Resection for Non-Functional Neuroendocrine Liver Metastasis: Does the Presence of Unresected Primary Tumor or Extrahepatic Metastatic Disease Matter?Publication . Xiang, JX; Zhang, XF; Beal, EW; Weiss, M; Aldrighetti, L; Poultsides, GA; Bauer, TW; Fields, RC; Maithel, SKumar; Pinto Marques, H; Pawlik, TMOBJECTIVES: The objective of this study was to assess the impact of unresected primary tumor, as well as extrahepatic metastasis, on the long-term prognosis of patients undergoing hepatic resection for non-functional neuroendocrine liver metastasis (NF-NELM). METHODS: Patients who underwent hepatic resection for NF-NELM were identified from a multi-institutional database. Data on clinical and pathological details, as well as the long-term overall survival (OS) were obtained and compared. Propensity score matching was performed to generate matched pairs of patients. RESULTS: Among the 332 patients with NF-NELM, 281 (84.6%) underwent primary tumor resection, while 51 (15.4%) did not. Patients who underwent primary resection were more likely to have a pancreatic primary and metachronous NELM. The long-term OS of patients who did and did not have the primary neuroendocrine tumor (NET) resected was comparable on both unmatched (10-year survival rate 66.8% vs. 54.0%, p = 0.192) and matched (10-year survival rate 75.7% vs. 60.4%, p = 0.271) analyses. In contrast, patients with NF-NELM and extrahepatic metastasis had a worse OS following resection compared with patients who had intrahepatic-only metastasis on unmatched (10-year survival rate 37.5% vs. 69.3%, p = 0.002) and matched (10-year survival rate 37.5% vs. 86.3%, p = 0.011) analyses. On multivariable analysis, while resection of the primary NET was not associated with OS (hazard ratio [HR] 0.7, 95% confidence interval [CI] 0.4-1.2, p = 0.195), the presence of extrahepatic metastasis was independently associated with long-term risk of death (HR 3.9, 95% CI 1.7-9.2, p = 0.002). CONCLUSIONS: While surgery should be considered for patients with NF-NELM who have an unresectable primary tumor, operative resection of NF-NELM may not be as beneficial in patients with extrahepatic disease.
- Higher Tumor Burden Status Dictates the Impact of Surgical Margin Status on Overall Survival in Patients Undergoing Resection of Intrahepatic CholangiocarcinomaPublication . Endo, Y; Sasaki, K; Moazzam, Z; Lima, H; Alaimo, L; Guglielmi, A; Aldrighetti, L; Weiss, M; Bauer, T; Alexandrescu, S; Poultsides, G; Kitago, M; Maithel, S; Pinto Marques, H; Martel, G; Pulitano, C; Shen, F; Cauchy, F; Koerkamp, B; Endo, I; Pawlik, TBackground: The present study aimed to examine the prognostic significance of margin status following hepatectomy of intrahepatic cholangiocarcinoma (ICC) relative to overall tumor burden and nodal status. Method: Patients who underwent curative-intent surgery for ICC between 1990 and 2017 were included from a multi-institutional database. The impact of margin status and width on overall survival (OS) was examined relative to TBS and preoperative nodal status. Results: Among 1105 patients with ICC who underwent resection, median tumor burden score (TBS) was 6.1 (IQR 4.2-8.8) and 218 (19.7%) patients had N1 disease. More than one in eight patients had an R1 surgical margin (n = 154, 13.9%). Among patients with low or medium TBS, an increasing margin width was associated with an incrementally improved 5-year OS (R1 31.9% vs. 1-3 mm 38.5% vs. 3-10 mm 48.0% vs. ≥ 10 mm 52.3%). In contrast, among patients with a high TBS, margin width was not associated with better survival (R1 28.9% vs. 1-3 mm 22.8% vs. 3-10 mm 29.6% vs. ≥ 10 mm 13.7%). In addition, surgical margin status did not impact survival with cutoffs of TBS 7 or greater. Furthermore, patients with low or medium TBS and preoperative negative lymph nodes derived a survival benefit from an R0 resection (R1 resection, HR 2.15, 95% CI 1.35-3.44, p = 0.001). In contrast, margin status was not associated with prognosis among patients with a high TBS and preoperative positive/suspicious lymph nodes (R1 resection, HR 1.34, 95% CI 0.58-3.11, p = 0.50). Conclusion: R0 resection and wider margin resection resulted in improved outcomes in patients with low tumor burden; however, the survival benefit of negative margin status disappeared in patients with underlying poor tumor biology.