Browsing by Author "Lamelas, J"
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- Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical ResectionPublication . Spolverato, G; Kim, Y; Alexandrescu, S; Pinto Marques, H; Lamelas, J; Aldrighetti, L; Clark Gamblin, T; Maithel, SK; Pulitano, C; Bauer, TW; Shen, F; Poultsides, GA; Tran, TB; Wallis Marsh, J; Pawlik, TMBACKGROUND: Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. METHODS: Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed. RESULTS: A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT (p < 0.001). CONCLUSIONS: Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit.
- Pancreas Rejection in the Artificial Intelligence Era: New Tool for Signal Patients at RiskPublication . Vigia, E; Ramalhete, L; Ribeiro, R; Barros, I; Chumbinho, B; Filipe, E; Pena, A; Bicho, L; Nobre, A; Carrelha, S; Sobral, M; Lamelas, J; Coelho, JS; Ferreira, A; Pinto Marques, HIntroduction: Pancreas transplantation is currently the only treatment that can re-establish normal endocrine pancreatic function. Despite all efforts, pancreas allograft survival and rejection remain major clinical problems. The purpose of this study was to identify features that could signal patients at risk of pancreas allograft rejection. Methods: We collected 74 features from 79 patients who underwent simultaneous pancreas-kidney transplantation (SPK) and used two widely-applicable classification methods, the Naive Bayesian Classifier and Support Vector Machine, to build predictive models. We used the area under the receiver operating characteristic curve and classification accuracy to evaluate the predictive performance via leave-one-out cross-validation. Results: Rejection events were identified in 13 SPK patients (17.8%). In feature selection approach, it was possible to identify 10 features, namely: previous treatment for diabetes mellitus with long-term Insulin (U/I/day), type of dialysis (peritoneal dialysis, hemodialysis, or pre-emptive), de novo DSA, vPRA_Pre-Transplant (%), donor blood glucose, pancreas donor risk index (pDRI), recipient height, dialysis time (days), warm ischemia (minutes), recipient of intensive care (days). The results showed that the Naive Bayes and Support Vector Machine classifiers prediction performed very well, with an AUROC and classification accuracy of 0.97 and 0.87, respectively, in the first model and 0.96 and 0.94 in the second model. Conclusion: Our results indicated that it is feasible to develop successful classifiers for the prediction of graft rejection. The Naive Bayesian generated nomogram can be used for rejection probability prediction, thus supporting clinical decision making.
- Performance of Prognostic Scores and Staging Systems in Predicting Long-Term Survival Outcomes After Surgery for Intrahepatic CholangiocarcinomaPublication . Buettner, S; Galjart, B; van Vugt, JL; Bagante, F; Alexandrescu, S; Pinto Marques, H; Lamelas, J; Aldrighetti, L; Gamblin, TC; Maithel, SK; Pulitano, C; Margonis, GA; Weiss, M; Bauer, TW; Shen, F; Poultsides, GA; Marsh, JW; IJzermans, JN; Groot Koerkamp, B; Pawlik, TMINTRODUCTION: We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center patient cohort. METHODS: The overall (OS) and disease free survival (DFS) prognostic discriminatory ability of various commonly used models were assessed in a large retrospective cohort. Harrell's concordance index (c-index) was used to determine accuracy of model prediction. RESULTS: Among 1054 ICC patients, median OS was 37.7 months and 1-, 3-, and 5-year survival, were 78.8%, 51.5%, and 39.3%, respectively. Recurrence of disease occurred in 454 (43.0%) patients with a median DFS of 29.6 months. One-, 3- and 5- year DFS were 64.6%, 46.5 % and 44.4%, respectively. The prognostic models associated with the best OS prediction were the Wang nomogram (c-index 0.668) and the Nathan staging system (c-index 0.639). No model was proficient in predicting DFS. Only the Wang nomogram exceeded a c-index of 0.6 for DFS (c-index 0.602). The c-index for the AJCC staging system was 0.637 for OS and 0.582 for DFS. CONCLUSIONS: While the Wang nomogram had the best discriminatory ability relative to OS and DFS, no ICC staging system or nomogram demonstrated excellent prognostic discrimination. The AJCC staging for ICC performed reasonably, although its overall discrimination was only modest-to-good.
- Predicting Function Delay with a Machine Learning Model: Improve the Long-term Survival of Pancreatic GraftsPublication . Vigia, E; Ramalhete, L; Barros, I; Chumbinho, B; Filipe, E; Pena, A; Bicho, L; Nobre, A; Carrelha, S; Corado, S; Sobral, M; Lamelas, J; Santos Coelho, J; Pinto Marques, H; Pico, P; Costa, S; Rodrigues, F; Bigotte Vieira, M; Magriço, R; Cotovio, P; Caeiro, F; Aires, I; Silva, C; Remédio, F; Martins, A; Ferreira, A; Paulino, J; Nolasco, F; Ribeiro, RThe impact of delayed graft function on outcomes following various solid organ transplants is well documented and addressed in the literature. Delayed graft function following various solid organ transplants is associated with both short- and long-term graft survival issues. In a retrospective cohort study including 106 patients we evaluated whether pancreas graft survival differs according to moment of insulin therapy following simultaneous pancreaskidney transplant. As a result, we aimed to identify possible risk factors and build a machine-learning-based model that predicts the likelihood of dysfunction following SPK transplant patients based on day zero data after transplant, allowing to enhance pancreatic graft survival. Feature selection by Relief algorithm yielded donor features, age, cause of death, hemoglobin, gender, ventilation days, days in ICU, length of cardiac respiratory arrest and recipient features, gender, long-term insulin, dialysis type, time of diabetes mellitus, vPRA pre-Tx, number of HLA-A mismatches and PRDI, all contributed to the models' strength.
- Survival after Resection of Multiple Tumor Foci of Intrahepatic CholangiocarcinomaPublication . Buettner, S; Ten Cate, D; Bagante, F; Alexandrescu, S; Pinto Marques, H; Lamelas, J; Aldrighetti, L; Gamblin, T; Maithel, S; Pulitano, C; Margonis, G; Weiss, M; Bauer, T; Shen, F; Poultsides, G; Marsh, J; IJzermans, J; Pawlik, T; Koerkamp, BBackground: Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci. Methods: Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ. Results: One thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2 months, while the median survival of patients with 2 tumors was 21.2 months; the median survival of patients with 3 or more tumors was 15.3 months (p < 0.001). Five-year survival was 43.3%, 28.0%, and 8.6%, respectively. The median survival of patients without OM was 37.8 months versus 14.9 months among patients with OM (p < 0.001); estimated 5-year survival was 39.3% and 10.6%, respectively. In multivariable analysis, the presence of two lesions was not an independent poor prognostic factor for OS (HR 1.19; 95%CI 0.90-1.57; p = 0.229). However, the presence of three or more tumors was an independent poor prognostic factor for OS (HR 1.97; 95%CI 1.48-2.64; p < 0.001). Conclusion: Resection of multiple liver tumors for patients with ICC did not preclude 5-year survival: in particular, estimated 5-year OS for resection of two tumors was 28.0%.
- The Effect of Preoperative Chemotherapy Treatment in Surgically Treated Intrahepatic Cholangiocarcinoma Patients-A Multi-Institutional AnalysisPublication . Buettner, S; Koerkamp, BG; Ejaz, A; Buisman, FE; Kim, Y; Margonis, GA; Alexandrescu, S; Pinto Marques, H; Lamelas, J; Aldrighetti, L; Gamblin, TC; Maithel, SK; Pulitano, C; Bauer, TW; Shen, F; Poultsides, GA; Marsh, JW; IJzermans, JN; Pawlik, TMINTRODUCTION: While preoperative chemotherapy (pCT) is utilized in many intra-abdominal cancers, the use of pCT among patients with intrahepatic cholangiocarcinoma (ICC) remains ill defined. As such, the objective of the current study was to examine the impact of pCT among patients undergoing curative-intent resection for ICC. METHODS: Patients who underwent hepatectomy for ICC were identified from a multi-institutional international cohort. The association between pCT with peri-operative and long-term clinical outcomes was assessed. RESULTS: Of the 1 057 patients who were identified and met the inclusion criteria, 62 patients (5.9%) received pCT. These patients were noticed to have more advanced disease. Median OS (pCT:46.9 months vs no pCT:37.4 months; P = 0.900) and DFS (pCT: 34.1 months vs no pCT: 29.1 months; P = 0.909) were similar between the two groups. In a subgroup analysis of propensity-score matched patients, there was longer OS (pCT:46.9 months vs no pCT:29.4 months) and DFS (pCT:34.1 months vs no pCT:14.0 months); however this did not reach statistical significance (both P > 0.05). CONCLUSION: In conclusion, pCT utilization among patients with ICC was higher among patients with more advanced disease. Short-term post-operative outcomes were not affected by pCT use and receipt of pCT resulted in equivalent OS and DFS following curative-intent resection.
- The Impact of Donor Risk Index, Recipients’ and Operative Characteristics on Post Liver Transplant One-Year Graft Failure: A Cohort AnalysisPublication . Cardoso, FS; Bagulho, L; Coelho, JS; Lamelas, J; Mateus, E; Mendes, M; Glória, H; Ribeiro, V; Mega, R; Pena, A; Pinto Marques, H; Germano, N; Nolasco, F; Perdigoto, R; Martins, ABackground and Aims: The donor risk index (DRI) quantifies donor-related characteristics potentially associated with increased risk of early graft failure. We aimed to assess the impact of the DRI, recipient and perioperative factors on post liver transplant (LT) outcomes. Methods: This was a singlecenter retrospective cohort study including all adult (≥18 years) patients who underwent LT from 01/2019 to 12/2019 at Curry Cabral Hospital, Lisbon, Portugal. Primary endpoint was 1-year graft failure post LT. Associations were studied with logistic regression. Results: A total of 131 cadaveric donor LT procedures were performed in 116 recipients. Recipients’ median (IQR) age was 57 (47–64) years and 101/131 (77.1%) were males. Cirrhosis was the underlying etiology in 95/131 (81.2%) transplants. Based on 8 predefined donors’ characteristics, median (IQR) DRI was 1.96 (1.67–2.16). Following adjustment for MELDNa score pre LT and SOFA score (adjusted odds ratio [aOR], 95% confidence interval [CI] = 0.91 [0.56–1.47]) or lactate (aOR [95% CI] = 2.76 [0.71–10.7]) upon intensive care unit (ICU) admission post LT, DRI was not associated with 1-year graft failure. However, higher SOFA score (aOR [95% CI] = 1.20 [1.05–1.37]) or lactate (aOR [95% CI] = 1.27 [1.10–1.46]) upon ICU admission post LT were independently associated with higher odds of 1-year graft failure. Conclusions: In a recent cohort of patients who underwent LT, DRI, despite being high, was not associated with 1-year graft failure, but SOFA score or lactate upon ICU admission post LT were.
- The Impact of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Among Patients with Intrahepatic CholangiocarcinomaPublication . Buettner, S; Spolverato, G; Kimbrough, CW; Alexandrescu, S; Pinto Marques, H; Lamelas, J; Aldrighetti, L; Gamblin, T; Maithel, SK; Pulitano, C; Weiss, M; Bauer, TW; Shen, F; Poultsides, GA; Marsh, JW; IJzermans, JN; Koerkamp, BG; Pawlik, TMBACKGROUND: Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma. METHODS: Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index). RESULTS: A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio were 2.7 (interquartile range [IQR]: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (≥5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (≥190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio <5 had a median survival of 47.1 months (95% CI: 37.9-53.3) compared with a median survival of 21.9 months (95% CI: 4.8-39.1) among patients with an neutrophil-to-lymphocyte ratio ≥5 (P = .001). In contrast, patients who had a platelets-to-lymphocyte ratio <190 vs platelets-to-lymphocyte ratio ≥190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival (hazard ratio: 1.04, 95% CI: 1.01-1.07; P = .002). Patients could be stratified into low- versus high-risk groups based on standard tumor-specific factors such as lymph node status, tumor size, number, and vascular invasion (C index 0.62). When neutrophil-to-lymphocyte ratio was added to the prognostic model, the discriminatory ability of the model improved (C index 0.71). CONCLUSION: Elevated neutrophil-to-lymphocyte ratio was independently associated with worse overall survival and improved the prognostic estimation of long-term survival among patients with intrahepatic cholangiocarcinoma undergoing resection.