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- Preoperative Risk Score (PreopScore) to Predict Overall Survival After Resection for Hepatocellular Carcinoma.Publication . Endo, Yutaka; Lima, Henrique A; Alaimo, Laura; Moazzam, Zorays; Brown, Zachary; Shaikh, Chanza F; Ratti, Francesca; Pinto Marques, Hugo; Soubrane, Olivier; Lam, Vincent; Poultsides, George A; Popescu, Irinel; Alexandrescu, Sorin; Martel, Guillaume; Workneh, Aklile; Guglielmi, Alfredo; Hugh, Tom; Aldrighetti, Luca; Shen, Feng; Endo, Itaru; Pawlik, Timothy M; ElsevierBackground: This study aimed to develop a holistic risk score incorporating preoperative tumor, liver, nutritional, and inflammatory markers to predict overall survival (OS) after hepatectomy for hepatocellular carcinoma (HCC). Methods: Patients who underwent curative-intent surgery for HCC between 2000 and 2020 were identified using an international multi-institutional database. Preoperative predictors associated with OS were selected and a prognostic risk score model (PreopScore) was developed and validated using cross-validation. Results: A total of 1676 patients were included. On multivariable analysis, preoperative parameters associated with OS included α-feto protein (hazard ratio [HR]1.17, 95%CI 1.03-1.34), neutrophil-to-lymphocyte ratio (HR2.62, 95%CI 1.30-5.30), albumin (HR0.49, 95%CI 0.34-0.70), gamma-glutamyl transpeptidase (HR1.00, 95%CI 1.00-1.00), as well as vascular involvement (HR3.52, 95%CI 2.10-5.89) and tumor burden score (medium, HR3.49, 95%CI 1.62-7.58; high, HR3.21, 95%CI 1.40-7.35) on preoperative imaging. A weighted PreopScore was devised and made available online (https://yutaka-endo.shinyapps.io/PrepoScore_Shiny/). Patients with a PreopScore 0-2, 2-3.5, and >3.5 had incrementally worse 5-year OS of 85.8%, 70.7%, and 52.4%, respectively (p < 0.001). The c-index of the test and validation cohort were 0.75 and 0.71, respectively. The PreopScore outperformed individual parameters and previous HCC staging systems. Discussion: The PreopScore can be used as a better guide to preoperatively identify patients and individualize pre-/post-operative strategies.
- Albumin-Bilirubin Grade and Tumor Burden Score Predict Outcomes Among Patients with Intrahepatic Cholangiocarcinoma After Hepatic Resection: a Multi-Institutional Analysis.Publication . Munir, Muhammad Musaab; Endo, Yutaka; Lima, Henrique A; Alaimo, Laura; Moazzam, Zorays; Shaikh, Chanza; Poultsides, George A; Guglielmi, Alfredo; Aldrighetti, Luca; Weiss, Matthew; Bauer, Todd W; Alexandrescu, Sorin; Kitago, Minoru; Maithel, Shishir K; Pinto Marques, Hugo; Martel, Guillaume; Pulitano, Carlo; Shen, Feng; Cauchy, François; Koerkamp, Bas Groot; Endo, Itaru; Pawlik, Timothy M; SpringerBackground: The prognostic role of tumor burden score (TBS) relative to albumin-bilirubin (ALBI) grade among patients undergoing curative-intent resection of ICC has not been examined. Methods: We identified patients who underwent curative-intent resection for ICC between 1990 and 2017 from a multi-institutional database. Multivariable analysis was performed to assess the effect of TBS relative to ALBI grade on both short- and long-term outcomes. Results: Among 724 patients, 360 (49.7%) patients had low TBS and low ALBI grade, 142 (19.6%) patients had low TBS and high ALBI grade, 138 (19.1%) patients had high TBS and low ALBI grade, and 84 patients (11.6%) had high TBS and high ALBI grade. Decreased tumor burden was associated with better long-term outcomes among patients with both low (5-year OS; low TBS vs. high TBS: 52.4% vs 21.4%; p < 0.001) and high ALBI grade (5-year OS; low TBS vs. high TBS: 40.7% vs 12.0%; p < 0.001). On multivariable analysis, higher ALBI grade was associated with greater odds of an extended hospital LOS (> 10 days) (OR 2.80, 95%CI 1.62-4.82; p < 0.001), perioperative transfusion (OR 2.04, 95%CI 1.25-3.36; p = 0.005), 90-day mortality (OR 2.56, 95%CI 1.12-5.81; p = 0.025), as well as a major complication (OR 1.99, 95%CI 1.13-3.49; p = 0.016) among patients with similar tumor burden. Of note, patients with high TBS and high ALBI grade had markedly worse overall survival compared with patients who had low TBS and low ALBI grade disease (HR 2.27; 95%CI 1.44-3.59; p < 0.001). Importantly, high TBS and high ALBI grade were strongly associated with both early recurrence (88.1%%) and 5-year risk of death (96.4%). Conclusion: Both TBS (i.e., tumor morphology) and ALBI grade (i.e., hepatic function reserve) were strong predictors of outcomes among patients undergoing ICC resection. There was an interplay between TBS and ALBI grade relative to patient prognosis after hepatic resection of ICC with high ALBI grade predicting worse outcomes among ICC patients with different TBS.
- Cirurgia Robótica em Patologia Colorretal: Análise dos Primeiros Três Anos de Atividade num Hospital do Serviço Nacional de Saúde em PortugalPublication . Carrola Gomes, D; Athayde Nemésio, R; Rodrigues, S; Penedo, J; Paixão, IIntrodução: A utilização da cirurgia minimamente invasiva no tratamento da patologia colorretal é hoje cientificamente aceite e o seu uso na prática clínica diária tem vindo a aumentar de forma sustentada. Diversos estudos indicam que a abordagem robótica pode trazer vantagens sobre a laparoscopia ‘convencional’, especialmente na cirurgia do reto. Este trabalho descreve e analisa os resultados dos primeiros três anos de cirurgia robótica na Unidade de Patologia Colorretal da Unidade Local de Saúde S. José. Métodos: Foram definidas as variáveis a analisar e construída uma base de dados prospetiva com os dados referentes aos doentes operados consecutivamente por três cirurgiões colorretais, acreditados internacionalmente na utilização do sistema Da Vinci Xi®, entre novembro de 2019 e outubro de 2022. A base de dados foi convertida numa versão anonimizada e foi sobre essa mesma que se procedeu à análise de dados. Foram analisados os dados de todos doentes operados nesse período. Resultados: Foram incluídos 80 doentes, 47 homens, mediana de idade de 70 anos e de IMC de 26 kg/m2. O score ASA era II em 53,7% e III em 41,3% dos doentes. Do total, 97,6% apresentavam doença maligna ou potencialmente maligna. Realizaram-se 34 colectomias proximais ao ângulo esplénico, 20 distais e 26 ressecções anteriores do reto. Houve ressecção síncrona de metástases hepáticas em dois casos. Foram analisados os resultados peri-operatórios a curto prazo e histopatológicos: duração (mediana): 300 minutos; perda hemática estimada (mediana): 50 mL; taxa de conversão: 2,5%; dias até retomar trânsito intestinal (mediana): três dias; dias de internamento (mediana): seis dias; taxa de complicações pós-operatórias: 20%, das quais 5% Clavien III e 0% Clavien IV/V; taxa de deiscência anastomótica: 2,5%; taxa de reintervenção: 2,5%; taxa de readmissão pós-alta: 1,3%; gânglios linfáticos ressecados (mediana): 20; taxa de ressecção R0: 100%; taxa de integridade mesorretal: 95,8% completo/quase completo. Conclusão: Os nossos resultados mostram que a introdução da cirurgia colorretal robótica no nosso centro foi segura e garantiu resultados clínicos a curto prazo e histopatológicos semelhantes ou favoráveis face aos descritos na literatura.
- Pancreatic Stone Protein As a Biomarker of SepsisPublication . Lopes, D; Chumbinho, B; Bandovas, JP; Faria, P; Espírito Santo, C; Ferreira, B; Val-Flores, L; Pereira, R; Germano, N; Bento, L
- Long-Term Recurrence-Free and Overall Survival Differ Based on Common, Proliferative, and Inflammatory Subtypes After Resection of Intrahepatic CholangiocarcinomaPublication . Alaimo, L; Moazzam, Z; Endo, Y; Lima, H; Ruzzenente, A; Guglielmi, A; Aldrighetti, L; Weiss, M; Bauer, T; Alexandrescu, S; Poultsides, G; Maithel, S; Pinto Marques, H; Martel, G; Pulitano, C; Shen, F; Cauchy, F; Koerkamp, B; Endo, I; Pawlik, TIntroduction: While generally associated with poor prognosis, intrahepatic cholangiocarcinoma (ICC) can have a heterogeneous presentation and natural history. We sought to identify specific ICC subtypes that may be associated with varied long-term outcomes and patterns of recurrence after liver resection. Methods: Patients who underwent curative-intent resection for ICC from 2000 to 2020 were identified from a multi-institutional database. Hierarchical cluster analysis characterized three ICC subtypes based on morphology (i.e., tumor burden score [TBS]) and biology (i.e., preoperative neutrophil-to-lymphocyte ratio [NLR] and CA19-9 levels). Results: Among 598 patients, the cluster analysis identified three ICC subtypes: Common (n = 300, 50.2%) (median, TBS: 4.5; NLR: 2.4; CA19-9: 38.0 U/mL); Proliferative (n = 246, 41.1%) (median, TBS: 8.8; NLR: 2.9; CA19-9: 71.2 U/mL); Inflammatory (n = 52, 8.7%) (median, TBS: 5.4; NLR: 12.6; CA19-9: 26.7 U/mL). Median overall survival (OS) (Common: 72.0 months; Proliferative: 31.4 months; Inflammatory: 22.9 months) and recurrence-free survival (RFS) (Common: 21.5 months; Proliferative: 11.9 months; Inflammatory: 9.0 months) varied considerably among the different ICC subtypes (all p < 0.001). Even though patients with Inflammatory ICC had more favorable T-(T1/T2, Common: 84.4%; Proliferative: 80.6%; Inflammatory: 86.5%) and N-(N0, Common: 14.0%; Proliferative: 20.7%; Inflammatory: 26.9%) disease, the Inflammatory subtype was associated with a higher incidence of intra- and extrahepatic recurrence (Common: 15.8%; Proliferative: 24.2%; Inflammatory: 28.6%) (all p = 0.01). Conclusions: Cluster analysis identified three distinct subtypes of ICC based on TBS, NLR, and CA19-9. ICC subtype was associated with RFS and OS and predicted worse outcomes among patients. Despite more favorable T- and N-disease, the Inflammatory ICC subtype was associated with worse outcomes ICC subtype should be considered in the prognostic stratification of patients.
- 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.
- Lymph Node Examination and Patterns of Nodal Metastasis Among Patients with Left- Versus Right-Sided Intrahepatic Cholangiocarcinoma After Major Curative-Intent ResectionPublication . Zhang, XF; Xue, F; Weiss, M; Popescu, Irinel; Pinto Marques, H; Aldrighetti, L; Maithel, S; Pulitano, C; Bauer, T; Shen, F; Poultsides, G; Cauchy, F; Martel, G; Koerkamp, B; Itaru, E; Lv, Y; Pawlik, TBackground: We sought to investigate whether the unique lateral patterns of lymphatic drainage impacted lymphadenectomy (LND), lymph node metastasis (LNM), and long-term survival of patients after curative hemi-hepatectomy for left- versus right-sided intrahepatic cholangiocarcinoma (ICC). Methods: Data on patients who underwent curative hemi-hepatectomy for left- or right-sided ICC were collected from 15 high-volume centers worldwide, as well as from the Surveillance, Epidemiology, and End Results (SEER) registry. Primary outcomes included overall survival (OS) and disease-free survival (DFS). Results: Among 697 patients identified from the multi-institutional database, patients who underwent hemi-hepatectomy for left-sided ICC (n = 363, 52.1%) were more likely to have an increased number of LND versus patients with right-sided ICC (n = 334, 47.9%) (median, left 5 versus right 3, p = 0.012), although the frequency (left 66.4% versus right 63.8%, p = 0.469) and station (beyond station no. 12, left 25.3% versus right 21.1%, p = 0.293) were similar. Consequently, left-sided ICC was associated with higher incidence of LNM (left 33.3% versus right 25.7%, p = 0.036), whereas the station and number of LNM were not different (both p > 0.1). There was no difference in OS (median, left 34.9 versus right 29.6 months, p = 0.130) or DFS (median, left 14.5 versus right 15.2 months, p = 0.771) among patients who underwent hemi-hepatectomy for left- versus right-sided ICC, which were also verified in the SEER dataset. LNM beyond station no. 12 was associated with even worse long-term survival versus LNM within station no. 12 among patients with either left- or right-sided ICC after curative-intent resection (all p < 0.05). Conclusions: The unique lateral patterns of lymphatic drainage were closely related to utilization of LND, as well as LNM of left- versus right-sided ICC.
- 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.
- TAC Score Better Predicts Survival Than the BCLC Following Resection of Hepatocellular CarcinomaPublication . Lima, H; Endo, Y; Moazzam, Z; Alaimo, L; Shaikh, C; Munir, M; Resende, V; Guglielmi, A; Pinto Marques, H; Cauchy, F; Lam, V; Poultsides, G; Popescu, I; Alexandrescu, S; Martel, G; Endo, I; Kitago, M; Shen, F; Pawlik, TBackground: Heterogeneity in hepatocellular carcinoma (HCC) still exists within the Barcelona clinic liver cancer (BCLC) subcategories. We developed a simple model to better discriminate and predict prognosis following resection. Methods: Patients who underwent curative-intent resection for HCC were identified from a multi-institutional database. Predictive factors of survival were identified to develop TAC (tumor burden score [TBS], alpha-fetoprotein [AFP], Child-Pugh CP]) score. Results: Among 1435 patients, median TBS was 5.1 (interquartile range [IQR]: 3.2-8.1), median AFP was 18.3 ng/ml (IQR 4.0-362.5), and 1391 (96.9%) patients were classified as CP-A. Factors associated with overall survival (OS) included TBS (low: referent; medium: HR 2.26, 95% CI: 1.73-2.96; high: HR = 3.35, 95% CI: 2.22-5.07), AFP (<400 ng/ml: referent; >400 ng/ml: HR = 1.56, 95% CI: 1.27-1.92), and CP (A: referent; B: HR = 1.81, 95% CI: 1.12-2.92) (all p < 0.05). A simplified risk score demonstrated superior concordance index, Akaike information criteria, homogeneity, and area under the curve versus BCLC (0.620 vs. 0.541; 5484.655 vs. 5536.454; 60.099 vs. 16.194; 0.62 vs. 0.55, respectively), and further stratified patients within BCLC groups relative to OS (BCLC 0, very low: 86.8%, low: 47.8%) (BCLC A, very low: 79.7%, low: 68.1%, medium: 52.5%, high: 35.6%) (BCLC B, low: 59.8%, medium: 43.7%, high: N/A). Conclusion: TAC is a simple, holistic score that consistently outperformed BCLC relative to discrimination power and prognostication following resection of HCC.
- Tumor Burden Score and Serum Alpha-fetoprotein Subclassify Intermediate-Stage Hepatocellular CarcinomaPublication . Lima, H; Endo, Y; Alaimo, L; Moazzam, Z; Munir, M; Shaikh, C; Resende, V; Guglielmi, A; Pinto Marques, H; Cauchy, F; Lam, V; Poultsides, G; Popescu, I; Alexandrescu, S; Martel, G; Hugh, T; Endo, I; Kitago, M; Shen, F; Pawlik, TBackground: Resection of Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) remains controversial. While not recommended by the BCLC algorithm, some patients may indeed benefit from hepatectomy. We sought to identify that subset of patients who might derive long-term survival benefit from resection. Methods: Intermediate-stage HCC patients who underwent curative-intent resection were identified from an international multi-institutional database. Factors associated with long-term prognosis were identified using multivariate analysis and a risk score was developed and assessed. Results: Among 194 patients, most individuals had two tumors (n = 123, 63.4%) with a median size of 6.0 cm (IQR, 4.0-8.4) for a median tumor burden score (TBS) of 6.5 (IQR, 5.0-9.1); median alpha-fetoprotein (AFP) was 23.9 ng/mL (IQR, 5.0-503.2), and median overall survival (OS) was 69 months (IAR, 60.7-77.3). Factors associated with OS included AFP (referent ≤ 20 ng/mL, > 20 ng/mL: HR 1.78 95%CI, 1.09-2.89) and TBS (referent TBS ≤ 8.0, TBS > 8.0: HR 1.72 95%CI, 1.07-2.75). While 71 (36.6%) patients had neither risk factor, 79 (40.7%) and 44 (22.7%) had 1 or 2, respectively. A simplified score stratified patients relative to recurrence-free survival (RFS) (0: 33.6% vs. 1: 18.0% vs. 2: 14.7%) (AUC 0.60) and recurrence time (i.e., < 6 months after surgery) (0: 21.3% vs. 1: 43.1% vs. 2: 68.6%) (AUC 0.69) (both p < 0.001). Of note, a higher score was also associated with incrementally worse 5-year OS (0: 68.1% vs. 1: 61.0% vs. 2: 29.9%) (AUC 0.62) (p < 0.001). Conclusion: Long-term OS and RFS outcomes varied considerably. Using a simple risk score, patients with low AFP and low TBS were identified as the subset of individuals most likely to benefit from resection.