ORCID Profile
0000-0003-3540-0488
Current Organisation
Universidade Nova de Lisboa
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
DOI: 10.1016/J.JAMCOLLSURG.2017.12.011
Abstract: Accurate prediction of prognosis for patients with intrahepatic cholangiocarcinoma (ICC) remains a challenge. We sought to define a preoperative risk tool to predict long-term survival after resection of ICC. Patients who underwent hepatectomy for ICC at 1 of 16 major hepatobiliary centers between 1990 and 2015 were identified. Clinicopathologic data were analyzed and a prognostic model was developed based on the regression β-coefficients on data in training set. The model was subsequently assessed using a validation set. Among 538 patients, most patients had a solitary tumor (median tumor number 1 interquartile range 1 to 2) and median tumor size was 5.7 cm (interquartile range 4.0 to 8.0 cm). Median and 5-year overall survival was 39.0 months and 39.0%, respectively. On multivariable analyses, preoperative factors associated with long-term survival included tumor size (hazard ratio [HR] 1.12 95% CI 1.06 to 1.18), natural logarithm carbohydrate antigen 19-9 level (HR 1.33 95% CI 1.22 to 1.45), albumin level (HR 0.76 95% CI 0.55 to 0.99), and neutrophil to lymphocyte ratio (HR 1.05 95% CI 1.02 to 1.09). A weighted composite prognostic score was constructed based on these factors: [9 + (1.12 × tumor size) + (2.81 × natural logarithm carbohydrate antigen 19-9) + (0.50 × neutrophil to lymphocyte ratio) + (-2.79 × albumin)]. The model demonstrated good performance in the testing (area under the curve 0.696) and validation (0.691) datasets. The model performed better than both the T categories (area under the curve 0.532) and the cumulative stage classifications in the American Joint Committee on Cancer staging manual, 8th edition (area under the curve 0.559). When assessing risk of death within 1 year of operation, a risk score ≥25 had a positive predictive value of 59.8% compared with a positive predictive value of 35.3% for American Joint Committee on Cancer staging manual, 8th edition T4 disease and 31.8% for stage IIIB disease. Postsurgical long-term outcomes could be predicted using a composite weighted scoring system based on preoperative clinical parameters. The preoperative risk model can be used to inform patient to provider conversations and expectations before operation.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2019
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-08-2011
Abstract: To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival. From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20 P .001), multiple lesions (HR, 1.80 P = .001), and vascular invasion (HR, 1.59 P = .015). Tumor size was not a prognostic factor (HR, 1.03 P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P .001). Lymphadenectomy was performed in 248 patients (55%) 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0 P .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34). Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.HPB.2021.02.009
Abstract: To improve the prognostic accuracy of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC) with establishment and validation of a modified TNM (mTNM) staging system. Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide (n = 643). An external validation dataset was obtained from the SEER registry (n = 797). The mTNM staging system was proposed by redefining T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1-2 LNM) and N2 (≥3 LNM). The 8th AJCC TNM staging system failed to stratify overall survival (OS) of stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV among all patients from the two databases, as well as stage I versus II, and stage III versus III among patients who had ≥6 LNs examined. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (Median OS, stage I 69.8 vs. II 37.1 vs. III 18.9 vs. IV 16.4 months, all p < 0.05), and SEER (Median OS, stage I 87.0 vs. II 29.3 vs. III 17.7 vs. IV 14.2 months, all p < 0.05) datasets, which was also verified among patients who had ≥6 lymph node harvested from both databases. The modified TNM staging system for ICC using the new T and N definitions provided an improved means to stratify patients relative to long-term OS versus the 8th AJCC staging.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.HPB.2017.06.008
Abstract: The benefit of adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma (ICC) is unclear. The aim of the current study was to investigate the impact of adjuvant chemotherapy on survival among patients undergoing resection of ICC using a multi-institutional database. 1154 ICC patients undergoing curative-intent hepatectomy between 1990 and 2015 were identified from 14 institutions. Cox proportional hazard modeling was used to determine the impact of adjuvant chemotherapy on overall survival (OS). Following resection, 347 (30%) patients received adjuvant chemotherapy, most commonly a gemcitabine-based regimen (n = 184, 52%). Patients with T2/T3/T4 disease were more likely to receive adjuvant therapy compared with patients with T1a/T1b disease (OR 2.5, 95%CI 1.89-3.23 P < 0.001). Among patients who did and did not receive adjuvant therapy, patients with T2/T3/T4 tumors had a 5-year OS of 37% (95%CI 28.9-44.4) versus 30% (95%CI 23.8-35.6), respectively (p = 0.006). Similarly patients with N1 disease who received adjuvant chemotherapy tended to have improved 5-year OS (18.3%, 95%CI 9.0-30.1 vs. no adjuvant therapy 12%, 95%CI 3.9-24.4 P = 0.050). While adjuvant chemotherapy did not influence the prognosis of all ICC patients following surgical resection, it was associated with a potential survival benefit in subgroups of patients at increased risk for recurrence, such as those with advanced tumors.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
Publisher: Springer Science and Business Media LLC
Date: 12-03-2015
DOI: 10.1245/S10434-015-4472-9
Abstract: The influence of margin status on long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to study the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ICC. From a multi-institutional database, 583 patients who underwent hepatic resection for ICC were identified. Demographics data, operative details, pathologic margin status, and long-term outcomes were collected and analyzed. Margin status was positive (R1) in 95 (17.8 %) patients among patients who underwent an R0 resection (80.9 %), margin width was negative by 1-4 mm in 166 (31.0 %) patients, 5-9 mm in 100 (18.7 %) patients, and ≥1 cm in 174 (32.5 %) patients. Overall, 379 (65.0 %) patients had a recurrence: 61.5 % intrahepatic, 13.5 % extrahepatic, and 25.0 % both intra- and extrahepatic. Median and 5-year RFS and OS was 10.0 months and 9.2 %, and 26.4 months and 23.0 %, respectively. Patients who had an R1 resection had a higher risk of recurrence (hazard ratio [HR] 1.61, 95 % CI 1.15-2.27 p = 0.01) and shorter OS (HR 1.54, 95 % CI 1.12-2.11). Among patients with an R0 resection, margin width was also associated with RFS (1-4 mm: HR 1.32, 95 % CI 0.98-1.78 vs. 5-9 mm: HR 1.21, 95 % CI 0.89-1.66) and OS (1-4 mm: HR 1.95, 95 % CI 0.45-2.63 vs. 5-9 mm: HR 1.21, 95 % CI 0.88-1.68) (referent ≥1 cm both p ≤ 0.002). Margin status and width remain independently associated with RFS and OS on multivariable analyses. For patients undergoing resection of ICC, R1 margin status was associated with an inferior long-term outcome. Moreover, there was an incremental worsening RFS and OS as margin width decreased.
Publisher: Oxford University Press (OUP)
Date: 28-11-2017
DOI: 10.1002/BJS.10676
Abstract: 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. 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. 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). 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.
Publisher: Wiley
Date: 20-01-2017
DOI: 10.1002/JSO.24524
Abstract: 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. 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. 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). 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.
Publisher: Radiological Society of North America (RSNA)
Date: 06-2021
Publisher: Wiley
Date: 14-02-2017
DOI: 10.1002/JSO.24569
Abstract: We sought to evaluate and validate the 8th edition of the AJCC classification using a multi-institutional cohort of patients with intrahepatic cholangiocarcinoma (ICC). 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. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2014
Publisher: Wiley
Date: 13-07-2017
DOI: 10.1002/JSO.24759
Abstract: We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center patient cohort. 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. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 25-01-2013
Publisher: Springer Science and Business Media LLC
Date: 19-04-2017
DOI: 10.1007/S11605-017-3426-X
Abstract: 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. Patients undergoing hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary centers were identified. 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). 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.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.HPB.2018.05.017
Abstract: Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC. The clinico-pathological characteristics and long-term outcomes of 1206 patients undergoing liver resection for ICC were compared based on the ICC morphological classification. Compared with MF patients, IG patients had a higher incidence of poor/un-differentiated tumor, lympho-vascular, and perineural invasion (poor/un-differentiated: MF, 18% vs. IG, 24% lympho-vascular invasion: MF, 30% vs. IG, 35% perineural invasion: MF, 17% vs. IG, 33% all p > 0.05). The pattern of recurrence was different among MF patients (intrahepatic only: 63% extrahepatic only: 22% both intra- and extrahepatic: 16%) versus IG patients (intrahepatic only: 46% extrahepatic: 25% both intra- and extrahepatic: 29%) (p < 0.001). Moreover, while 78% of patients with MF had an early recurrence (<18 months from surgery), 59% of IG patients had and early recurrence (p = 0.039). On multivariable analysis, after controlling for competing risk factors, IG patients had a similar prognosis as MF patients (HR 0.90, p = 0.69). While IG patients more frequently presented with more adverse pathological characteristics, the prognosis of IG patients was comparable with MF patients after controlling for all these adverse factors.
Publisher: Oxford University Press (OUP)
Date: 14-04-2018
DOI: 10.1002/BJS.10827
Abstract: The role of routine lymph node dissection (LND) in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The objective of this study was to investigate the trends of LND use in the surgical treatment of ICC. Patients undergoing curative intent resection for ICC in 2000–2015 were identified from an international multi-institutional database. Use of lymphadenectomy was evaluated over time and by geographical region (West versus East) LND use and final nodal status were analysed relative to AJCC T categories. Among the 1084 patients identified, half (535, 49·4 per cent) underwent concomitant hepatic resection and LND. Between 2000 and 2015, the proportion of patients undergoing LND for ICC nearly doubled: 44·4 per cent in 2000 versus 81·5 per cent in 2015 (P & 0·001). Use of LND increased over time among both Eastern and Western centres. The odds of LND was associated with the time period of surgery and the extent of the tumour/T status (referent T1a: OR 2·43 for T2, P = 0·001 OR 2·13 for T3, P = 0·016). Among the 535 patients who had LND, lymph node metastasis (LNM) was noted in 209 (39·1 per cent). Specifically, the incidence of LNM was 24 per cent in T1a disease, 22 per cent in T1b, 42·9 per cent in T2, 48 per cent in T3 and 66 per cent in T4 (P & 0·001). AJCC T3 and T4 categories, harvesting of six or more lymph nodes, and presence of satellite lesions were independently associated with LNM. The rate of LNM was high across all T categories, with one in five patients with T1 disease having nodal metastasis. The trend in increased use of LND suggests a growing adoption of AJCC recommendations in the treatment of ICC.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.SURG.2018.05.002
Abstract: 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. 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). 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 .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). 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.
Publisher: American Medical Association (AMA)
Date: 05-2014
DOI: 10.1001/JAMASURG.2013.5168
Abstract: Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the liver that is increasing in incidence, and the prognostic factors associated with outcome after surgery remain poorly defined. To combine clinicopathologic variables associated with overall survival after resection of ICC into a prediction nomogram. We performed an international multicenter study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from May 1, 1990, through December 31, 2011. Multivariate Cox proportional hazards regression modeling with backward selection using the Akaike information criteria was used to select variables for construction of the nomogram. Discrimination and calibration were performed using Kaplan-Meier curves and calibration plots. Surgical resection of ICC at a participating hospital. Long-term survival, effect of potential prognostic factors, and performance of proposed nomogram. Median patient age was 59.2 years, and 53.1% of the patients were male. Most patients (74.7%) had a solitary tumor, and median tumor size was 6.0 cm. Patients were treated with an extended hepatectomy (202 [39.3%]), a hemihepatectomy (180 [35.0%]), or a minor liver resection (<3 segments) (132 [25.7%]). Most patients underwent R0 resection (87.9%), and 35.7% of patients had N1 disease. Using the backward selection of clinically relevant variables, we found that age at diagnosis (hazard ratio [HR], 1.31 P < .001), tumor size (HR, 1.50 P < .001), multiple tumors (HR, 1.58 P < .001), cirrhosis (HR, 1.51 P = .08), lymph node metastasis (HR, 1.78 P = .01), and macrovascular invasion (HR, 2.10 P < .001) were selected as factors predictive of survival. On the basis of these factors, a nomogram was created to predict survival of ICC after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.692). On the basis of an Eastern and Western experience, a nomogram was developed to predict overall survival after resection for ICC. Validation revealed good discrimination and calibration, suggesting clinical utility to improve in idualized predictions of survival for patients undergoing resection of ICC.
Publisher: Springer Science and Business Media LLC
Date: 31-05-2019
DOI: 10.1245/S10434-019-07483-9
Abstract: Although lymph node metastasis (LNM) is an important prognostic indicator for patients with intrahepatic cholangiocarcinoma (ICC), the benefit and indication for lymphadenectomy remain unclear. Patients diagnosed with ICC between 1990 and 2016 were identified in the international multi-institutional dataset. To determine the survival benefit from lymphadenectomy, the therapeutic index was calculated by multiplying the frequency of LNM in a particular group of patients by the 3-year cancer-specific survival (CSS) rate of patients with LNM in that subgroup. Among 471 patients who met the inclusion criteria, approximately half had LNM (n = 205, 43.5%). The median number of resected and metastatic LNs were 4 [interquartile range (IQR) 2-8] and 0 (IQR 0-1), respectively. Three-year CSS in the entire cohort was 29.9%, reflecting a therapeutic index value of 13.0. The therapeutic index was lower among patients with major vascular invasion (5.4), preoperative carcinoembryonic antigen (CEA) > 5.0 (8.2), and LNM in areas other than the hepatoduodenal ligament (5.2). Of note, a therapeutic index difference of more than 10 points was noted only when examining the number of LNs harvested [1-2 (4.1) vs. 3-6 (16.1) vs. ≥ 7 (17.8)]. The survival benefit derived from lymphadenectomy was poor among patients with major vascular invasion, CEA > 5.0, and LNM in areas other than the hepatoduodenal ligament. Resection of three or more LNs was associated with the highest therapeutic value among patients with LNM.
Publisher: Springer Science and Business Media LLC
Date: 10-12-2019
DOI: 10.1007/S11605-019-04472-X
Abstract: To assess conditional survival (CS) according to recurrence status, as well as conditional disease-free survival (cDFS) among patients with intrahepatic cholangiocarcinoma (ICC). 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. 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. CS and cDFS changed over time according to the presence of disease-specific risk factors, as well as the presence of recurrence.
Publisher: Springer Science and Business Media LLC
Date: 20-05-2014
DOI: 10.1007/S11605-014-2533-1
Abstract: The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection is controversial. We sought to define the incidence of major and microscopic vascular invasion relative to ICC tumor size, and identify predictors of microscopic vascular invasion in patients with ICC ≥5 cm. A total of 443 patients undergoing surgical resection for ICC between 1973 and 2011 at one of 11 participating institutions were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. As tumor sized increased, the incidence of microscopic vascular invasion increased: <3 cm, 3.6 % 3-5 cm, 24.7 % 5-7 cm, 38.3 % 7-15 cm, 32.9 %, ≥15 cm, 55.6 % (p < 0.001). Increasing tumor size was also found to be associated with worsening tumor grade. The incidence of poorly differentiated tumors increased with increasing ICC tumor size: 15 cm, 31.6 % (p = 0.04). The presence of perineural invasion (odds ratio [OR] = 2.98) and regional lymph node metastasis (OR = 4.43) were independently associated with an increased risk of microscopic vascular invasion in tumors ≥5 cm (both p < 0.05). Risk of microscopic vascular invasion and worse tumor grade increased with tumor size. Large tumors likely harbor worse pathologic features this information should be considered when determining therapy and prognosis of patients with large ICC.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2018
DOI: 10.1007/S11605-018-3682-4
Abstract: The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence. Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence. Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13 p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03 p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11 p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89 p 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered "favorable." A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.
Publisher: Wiley
Date: 15-04-2017
DOI: 10.1002/JSO.24633
Abstract: Major vascular involvement (IVC or portal vein) for intrahepatic cholangiocarcinoma (ICC) has traditionally been considered a contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing hepatectomy with major vascular resection in a large international multi-institutional database. A total of 1087 ICC patients who underwent curative-intent hepatectomy between 1990 and 2016 were identified from 13 institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative and survival outcomes. Of 1087 patients who underwent resection, 128 (11.8%) also underwent major vascular resection (21 [16.4%] IVC resections, 98 [76.6%] PV resections, 9 [7.0%] combined resections). Despite more advanced disease, major vascular resection was not associated with the risk of any complication (OR = 0.68, 95%CI 0.32-1.45) or major complications (OR = 0.95, 95%CI 0.49-2.00). Post-operative mortality was also comparable between groups (OR = 1.05, 95%CI 0.32-3.47). In addition, median recurrence-free (14.0 vs 14.7 months, HR = 0.737, 95%CI 0.49-1.10) and overall (33.4 vs 40.2 months, HR = 0.71, 95%CI 0.359-1.40) survival were similar among patients who did and did not undergo major vascular resection (both P > 0.05). Among patients with ICC, major vascular resection was not associated with worse perioperative or oncologic outcomes. Concurrent major vascular resection should be considered in appropriately selected patients with ICC undergoing hepatectomy.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2015
DOI: 10.1007/S11605-015-2826-Z
Abstract: The objective of the current study was to define the incidence of 30-day readmission after hepatic resection for intrahepatic cholangiocarcinoma (ICC). In particular, we sought to identify risk factors associated with a higher risk of readmission among patients undergoing resection for ICC. Patients who underwent hepatic resection for ICC at 12 major hepatobiliary centers in the USA, Europe, Australia, and Asia between 1990 and 2013 were identified. Thirty-day readmission and clinicopathologic characteristics associated with higher risk of readmission were examined. Among 602 patients, 401 (68.3%) patients underwent a major hepatectomy and 256 (43.3%) experienced at least one post-operative complication. Overall 30-day readmission was 7.8% (n = 47). Risk factors associated with readmission included pre-operative jaundice (odds ratio (OR) 2.45) and the presence of a major complication (OR 3.38). In fact, 95.7% of readmitted patients had experienced a post-operative complication versus only 38.8% of non-readmitted patients (P < 0.001). Among patients who were readmitted, repeat hospitalization was associated with a median LOS of 6.5 days (interquartile range (IQR) 4.0-11.5) and one patient died during readmission. Readmission after hepatic resection for ICC occurred in 1 in 13 patients. Patients with pre-operative jaundice and those who experienced a complication had over a threefold higher risk of being readmitted.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2017
DOI: 10.1007/S11605-017-3550-7
Abstract: 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. 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). 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 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. 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2015
DOI: 10.1016/J.JAMCOLLSURG.2015.09.012
Abstract: The role of routine lymphadenectomy (LD) among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) remains poorly defined. This study aimed to evaluate the role of routine LD as well as to quantify the impact of not assessing nodal station on disease-specific survival (DSS) among patients undergoing liver surgery for ICC. Using data from 12 major hepatobiliary centers, 561 patients undergoing liver surgery for ICC between 1990 and 2012 were identified. The association between nodal status and DSS was assessed using Cox proportional and Aalen's linear hazards models. Among the 272 (48.5%) patients who underwent LD, 123 (45.2%) had lymph node metastasis (N1). Although differences in DSS were noted between N0 and Nx patients within the first 18 months after surgery (DSS at 18 months: N0 vs Nx, 70.2% vs 60.6%, respectively, p = 0.019) among patients who had survived to 18 months, the DSS at 60 months of Nx patients was comparable to that of N0 patients (p = 0.48). Conversely, although the DSS of N1 and Nx patients was comparable in the short-term (DSS at 18 months: p = 0.13), among patients who had survived to 18 months, N1 patients had a lower DSS compared with Nx patients (DSS at 60 months among patients who had survived to 18 months: N1 vs Nx, 15.2% vs 45.8%, respectively, p < 0.001 all p values were based on the log-rank test comparing 2 survival curves). Although Nx patients and N1 patients had comparable DSS in the short-term, Nx patients who survived past 18 months had a survival comparable to that of N0 patients. Lack of nodal staging may lead to heterogeneous and potentially incorrect prognostic classification of patients with ICC.
Publisher: Springer Science and Business Media LLC
Date: 02-05-2017
DOI: 10.1245/S10434-017-5870-Y
Abstract: The influence of morphological status on the long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) is poorly defined. We sought to study the impact of morphological status on overall survival (OS) of patients undergoing curative-intent resection for ICC. A total of 1083 patients who underwent liver resection for ICC between 1990 and 2015 were identified. Data on clinicopathological characteristics, operative details, and morphological status were recorded and analyzed. A propensity score-matched analysis was performed to reduce confounding biases. Among 1083 patients, 941(86.9%) had a mass-forming (MF) or intraductal-growth (IG) type, while 142 (13.1%) had a periductal-infiltrating (PI) or MF with PI components (MF + PI) ICC. Patients with an MF/IG ICC had a 5-year OS of 41.8% (95% confidence interval [CI] 37.7-45.9) compared with 25.5% (95% CI 17.3-34.4) for patients with a PI/MF + PI (p < 0.001). Morphological type was found to be an independent predictor of OS as patients with a PI/MF + PI ICC had a higher hazard of death (hazard ratio [HR] 1.42, 95% CI 1.11-1.82 p = 0.006) compared with patients who had an MF/IG ICC. Compared with T1a-T1b-T2 MF/IG tumors, T1a-T1b-T2 PI/MF + PI and T3-T4 PI/MF + PI tumors were associated with an increased risk of death (HR 1.47 vs. 3.59). Conversely, patients with T3-T4 MF/IG tumors had a similar risk of death compared with T1a-T1b-T2 MF/IG patients (p = 0.95). Among patients undergoing curative-intent resection of ICC, morphological status was a predictor of long-term outcome. Patients with PI or MF + PI ICC had an approximately 45% increased risk of death long-term compared with patients who had an MF or IG ICC.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2020
Publisher: Springer Science and Business Media LLC
Date: 14-11-2019
DOI: 10.1245/S10434-019-08067-3
Abstract: Accurate risk stratification and patient selection is necessary to identify patients who will benefit the most from surgery or be better treated with other non-surgical treatment strategies. We sought to identify which patients in the preoperative setting would likely derive the most or least benefit from resection of intrahepatic cholangiocarcinoma (ICC). Patients who underwent curative-intent resection for ICC between 1990 and 2017 were identified from an international multi-institutional database. A machine-based classification and regression tree (CART) was used to generate homogeneous groups of patients relative to overall survival (OS) based on preoperative factors. Among 1146 patients, CART analysis revealed tumor number and size, albumin-bilirubin (ALBI) grade and preoperative lymph node (LN) status as the strongest prognostic factors associated with OS among patients undergoing resection for ICC. In turn, four groups of patients with distinct outcomes were generated through machine learning: Group 1 (n = 228): single ICC, size ≤ 5 cm, ALBI grade I, negative preoperative LN status Group 2 (n = 708): (1) single tumor > 5 cm, (2) single tumor ≤ 5 cm, ALBI grade 2/3, and (3) single tumor ≤ 5 cm, ALBI grade 1, metastatic/suspicious LNs Group 3 (n = 150): 2-3 tumors Group 4 (n = 60): ≥ 4 tumors. 5-year OS among Group 1, 2, 3, and 4 patients was 60.5%, 35.8%, 27.5%, and 3.8%, respectively (p < 0.001). Similarly, 5-year disease-free survival (DFS) among Group 1, 2, 3, and 4 patients was 47%, 27.2%, 6.8%, and 0%, respectively (p < 0.001). The machine-based CART model identified distinct prognostic groups of patients with distinct outcomes based on preoperative factors. Survival decision trees may be useful as guides in preoperative patient selection and risk stratification.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2013
Publisher: American Medical Association (AMA)
Date: 06-2015
DOI: 10.1001/JAMASURG.2015.0219
Abstract: Whereas conventional actuarial overall survival (OS) estimates rely exclusively on static factors determined around the time of surgery, conditional survival (CS) estimates take into account the years that a patient has already survived. To define the CS of patients following liver resection for intrahepatic cholangiocarcinoma (ICC). Between January 1, 1990, and December 31, 2013, a total of 535 patients who underwent resection of ICC were identified from an international multi-institutional database. In this retrospective international study conducted from January to June 2014, clinicopathological characteristics, operative details, and long-term survival data were analyzed. Conditional survival estimates were calculated as the probability of survival for an additional 3 years. Resection of ICC. Overall survival and CS. While actuarial OS decreased over time from 39% at 3 years to 16% at 8 years (P = .002), the 3-year CS (CS₃) increased over time among those patients who survived. The CS₃ at 5 years-the probability of surviving to postoperative year 8 after having already survived to postoperative year 5-was 65% compared with 8-year OS of 16% (P = .002). Factors that were associated with worse OS included larger tumor size (hazard ratio [HR], 1.02 95% CI, 1.00-1.05 P = .05), multifocal disease (HR, 1.49 95% CI, 1.19-1.86 P = .01), lymph node metastasis (HR, 2.21 95% CI, 1.67-2.93 P < .01), and vascular invasion (HR, 1.39 95% CI, 1.10-1.75 P = .006). The calculated CS₃ exceeded the actuarial survival for all high-risk subgroups. For ex le, patients with lymph node metastasis had an actuarial OS of 11% at 6 years vs a CS₃ of 49% at 3 years (Δ38%). Similarly, patients with vascular invasion had an actuarial OS of 15% at 6 years compared with a CS₃ of 50% at 3 years (Δ35%). Conditional survival estimates may provide critical quantitative information about the changing probability of survival over time among patients undergoing liver resection for ICC. Therefore, such estimates can be of significant value to patients and health care professionals.
Publisher: American Medical Association (AMA)
Date: 19-06-2019
Publisher: Springer Science and Business Media LLC
Date: 03-01-2018
DOI: 10.1007/S00268-017-4453-1
Abstract: The consequences of lymphadenectomy (LND) on cirrhotic patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) have not been investigated. We sought to analyze the impact of LND on morbidity among patients undergoing resection for ICC. A total of 1005 patients who underwent hepatectomy for ICC at one of the 14 participating institutions between 1990 and 2015 were identified. A propensity score match analysis was performed to reduce confounding biases between cirrhosis and non-cirrhosis groups. Cirrhosis was diagnosed in 118 (11.7%) patients. Among non-cirrhotic patients, 63% underwent major liver resection versus only 20% among patients with cirrhosis (p < 0.001). LND was also less common among cirrhotic versus non-cirrhotic patients (19 vs. 50%, p < 0.001). The incidence of complications was 41 and 30% among patients who did not and did have cirrhosis, respectively (p = 0.022). The propensity-matched cohort included 150 patients. The incidence of complications was 71% among patients who underwent lymphadenectomy versus 23% among patients who did not undergo lymphadenectomy (OR 8.39) (p < 0.001). In the propensity-matched analysis, the median HLN was comparable among patients independent of cirrhosis status (median HLN: non-cirrhosis, 2.5 vs. cirrhosis, 2) (p = 0.95). While lymphadenectomy was associated with a higher risk of infections (non-cirrhosis, 0% vs. cirrhosis, 21%, p < 0.001) among patients with cirrhosis, infections were not associated with lymphadenectomy among non-cirrhotic patients (p = 0.19). Lymphadenectomy was associated with an increased risk of complications among patients with cirrhosis undergoing surgery for ICC. The benefit of lymphadenectomy in cirrhotic patients should be considered in light of the higher risk of postoperative complications compared with non-cirrhotic patients.
Publisher: Elsevier BV
Date: 06-0012
DOI: 10.1016/J.EJSO.2019.03.004
Abstract: The association between body mass index (BMI) and long-term outcomes of patients with ICC has not been well defined. We sought to define the presentation and oncologic outcomes of patients with ICC undergoing curative-intent resection, according to their BMI category. Patients who underwent resection of ICC were identified in a multi-institutional database. Patients were categorized as normal weight (BMI 18.5-24.9 kg/m Among a total of 790 patients undergoing curative-intent resection of ICC in the analytic cohort, 399 (50.5%) had normal weight, 274 (34.7%) were overweight and 117 (14.8%) were obese. Caucasian patients were more likely to be obese (66.7%, n = 78) and overweight (47.1%, n = 129) compared with Asian (obese: 18.8%, n = 22 overweight: 46%, n = 126) and other races (obese: 14.5%, n = 17 overweight: 6.9%, n = 19)(p 0.05). On multivariable analysis, increased BMI was an independent risk factor for tumor recurrence (OR 1.16, 95% CI 1.02-1.32, for every 5 unit increase). Increasing BMI was associated with incremental increases in the risk of recurrence following curative-intent resection of ICC. Future studies should aim to achieve a better understanding of BMI-related factors relative to prognosis of patients with ICC.
Publisher: Springer Science and Business Media LLC
Date: 15-08-2008
DOI: 10.1007/S11605-008-0652-2
Abstract: The surgical management of hepatocellular carcinoma in patients with well-compensated cirrhosis is controversial. The purpose of the current study was to compare the outcome of patients with well-compensated cirrhosis and early stage hepatocellular carcinoma treated with initial hepatic resection versus transplantation. Between 1985 and 2008, 245 patients underwent hepatic resection, and 134 patients underwent liver transplantation for early stage hepatocellular carcinoma. All patients had well-compensated cirrhosis. Prognostic factors were evaluated using univariate and multivariate analyses survival was calculated using the Kaplan-Meier method. Compared with transplantation, patients undergoing resection had larger tumors and a higher incidence of microscopic vascular invasion. Transplantation was associated with better 5-year disease-free and overall survival compared with resection. Hepatitis status, presence of microscopic vascular invasion, and tumor size were predictors for recurrence, while the presence of microscopic vascular invasion and tumor size conferred an increased risk of death. The disease-free survival advantage with transplantation was more pronounced in hepatitis C patients compared with non-hepatitis and hepatitis B patients. The overall survival advantage with transplantation persisted in cases of solitary lesions < or = 3 cm, but was attenuated in patients with a MELD score < or = 8. In well-compensated cirrhotic patients with early stage hepatocellular carcinoma, transplantation was associated with longer disease-free and overall survival. Patients undergoing resection did, however, have tumors with more advanced pathologic features. Patients best suited for initial resection as the treatment of hepatocellular carcinoma were those with a MELD score </= 8 without evidence of hepatitis.
Publisher: Springer Science and Business Media LLC
Date: 10-06-2015
DOI: 10.1245/S10434-015-4642-9
Abstract: 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. 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. 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). 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.
Publisher: Springer Science and Business Media LLC
Date: 29-03-2019
DOI: 10.1245/S10434-019-07336-5
Abstract: We sought to evaluate the utilization of lymphadenectomy (LND) and the incidence of lymph node metastasis (LNM) among different morphologic types of intrahepatic cholangiocarcinoma (ICC). Clinical data of patients undergoing curative-intent resection for ICC between 1990 and 2017 were collected and analyzed. The preoperative nodal status was evaluated by imaging studies, and the morphologic and lymph node (LN) status was collected on final pathology report. Overall, 1032 patients had a mass-forming (MF) or intraductal growth (IG) ICC subtype, whereas 150 patients had a periductal infiltrating (PI) or MF + PI subtype. Among the 924 patients with MF/IG ICC subtype who had nodal assessment on preoperative imaging, 747 (80.8%) were node-negative, whereas 177 (19.2%) patients were suspicious for metastatic nodal disease. On final pathological analysis, 71 of 282 (25.2%) patients who had preoperative node-negative disease ultimately had LNM. In contrast, 79 of 135 (58.5%) patients with preoperative suspicious/metastatic LNs had pathologically confirmed LNM (odds ratio [OR] 4.2, p < 0.001). Among the 129 patients with PI/MF + PI ICC subtype and preoperative nodal information, 72 (55.8%) were node-negative on preoperative imaging. In contrast, 57 (44.2%) patients had suspicious/metastatic LNs. On final pathologic examination, 45.3% (n = 24) of patients believed to be node-negative on preoperative imaging had LNM 68.0% (n = 34) of patients who had suspicious ositive nodal disease on imaging ultimately had LNM (OR 2.6, p = 0.009). Given the low accuracy of preoperative imaging evaluation of nodal status, routine LND should be performed at the time of resection for both MF/IG and PI/MF + PI ICC subtypes.
Publisher: Elsevier BV
Date: 08-2009
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.SURG.2018.01.001
Abstract: Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short- and long-term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma. A total of 912 patients with mass-forming peripheral intrahepatic cholangiocarcinoma, 101 patients with hilar type intrahepatic cholangiocarcinoma, and 159 patients with hilar cholangiocarcinoma undergoing curative resection from 2000 to 2015 were included from two multi-institutional databases. Clinicopathologic characteristics and short- and long-term outcomes were compared among the 3 groups. Patients with hilar type intrahepatic cholangiocarcinoma had more aggressive tumor characteristics (eg, higher frequency of vascular invasion and lymph nodes metastasis) and experienced more extensive resections in comparison with either peripheral intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma patients. The odds of lymphadenectomy and R0 resection rate among patients with hilar type intrahepatic cholangiocarcinoma were comparable with hilar cholangiocarcinoma patients, but higher than peripheral intrahepatic cholangiocarcinoma patients (lymphadenectomy incidence, 85.1% vs 42.5%, P < .001 R0 rate, 75.2% vs 88.8%, P < .001). After curative surgery, patients with hilar type intrahepatic cholangiocarcinoma experienced a higher rate of technical-related complications compared with peripheral intrahepatic cholangiocarcinoma patients. Of note, hilar type intrahepatic cholangiocarcinoma was associated with worse disease-specific survival and recurrence-free survival after curative resection versus peripheral intrahepatic cholangiocarcinoma (median disease-specific survival, 26.0 vs 54.0 months, P < .001 median recurrence-free survival, 13.0 vs 18.0 months, P = .021) and hilar cholangiocarcinoma (median disease-specific survival, 26.0 vs 49.0 months, P = .003 median recurrence-free survival, 13.0 vs 33.4 months, P < .001). Mass-forming intrahepatic cholangiocarcinoma with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma, which showed distinct clinicopathologic characteristics, worse long-term outcomes after curative resection, in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.SURG.2019.06.005
Abstract: Tumor burden is an important factor in defining prognosis among patients with primary and secondary liver cancers. Although the eighth edition of the American Joint Committee on Cancer staging system has changed the criteria for staging patients with intrahepatic cholangiocarcinoma to better define the effect of tumor burden on prognosis, the impact of intrahepatic cholangiocarcinoma tumor burden on overall survival has not been examined using a machine-learning tool. Patients who underwent resection of intrahepatic cholangiocarcinoma at 1 of 14 participating international hospitals between 1990 and 2015 were identified. Classical survival models and the Classification and Regression Tree model were used to identify groups of patients with a homogeneous risk of death and investigate the hierarchical association between variables and overall survival. Among 1,116 patients included in the analysis, tumor size was ≤5 cm in 447 (40.1%) patients and >5 cm in 669 (59.9%) patients. Although 82.9% (n = 926) of patients had a single intrahepatic cholangiocarcinoma, 9.9% (n = 110) and 7.2% (n = 80) of patients had 2 and ≥3 tumors, respectively. Patients with intrahepatic cholangiocarcinoma tumors ≤5 cm and >5 cm had a 5-year overall survival of 51.7% and 32.6%, respectively (P < 0.001). Five-year overall survival decreased from 44.6% among patients with a single intrahepatic cholangiocarcinoma to 28.1% and 14.2% among patients with 2 and ≥3 intrahepatic cholangiocarcinomas, respectively (P < 0.001). Among the combinations of tumor size and intrahepatic cholangiocarcinoma tumor number used to estimate tumor burden, logarithmic transformation of tumor size (log tumor size) and intrahepatic cholangiocarcinoma tumor number had the highest concordance index. The Classification and Regression Tree model identified 8 classes of patients with a homogeneous risk of death, illustrating the hierarchical relationship between tumor burden (log tumor size and number of intrahepatic cholangiocarcinomas) and other factors associated with prognosis. Intrahepatic cholangiocarcinoma tumor size and number demonstrated a strong nonlinear association with survival after resection of intrahepatic cholangiocarcinoma. A log-model Classification and Regression Tree-derived tumor burden score may be a better tool to estimate prognosis of patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2019
DOI: 10.1245/S10434-019-07353-4
Abstract: Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common. The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC. Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed. A total of 920 patients were included. With a median follow-up of 38 months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0 m) and extrahepatic-only recurrence (median 8.0 m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0 m p < 0.05). On multivariate analysis, surgical margin < 10 mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60 p = 0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22 p < 0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25 p = 0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7 months) versus other treatments (9.7 months) [p < 0.001]. Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.
Publisher: Elsevier BV
Date: 08-2012
Publisher: Springer Science and Business Media LLC
Date: 17-03-2022
DOI: 10.1245/S10434-022-11462-Y
Abstract: The prognostic impact of tumor necrosis among patients undergoing resection for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. Patients who underwent curative-intent resection for ICC between 2000 and 2017 were identified using a multi-institutional database. The association of pathologic tumor necrosis with overall survival (OS) and recurrence-free survival (RFS) was examined. Among 757 patients who underwent resection for ICC, tumor necrosis was present in 384 (50.7%) patients (no necrosis: n = 373, 49.3% <50% necrosis: n = 291, 38.4% ≥50% necrosis: n = 93, 12.3%). Tumor necrosis was associated with worse OS (5-year OS: no necrosis 39.3% vs. <50% necrosis 34.7% and ≥50% necrosis 24.0% p = 0.03) and RFS (5-year RFS: no necrosis 25.7% vs. <50% necrosis 13.9% and ≥50% necrosis 18.8% p < 0.001). After stratifying by T stage, tumor necrosis was able to further stratify prognosis among patients with T1a ICC (5-year RFS: T1a and no necrosis 46.7% vs. T1a and necrosis 36.1% p = 0.02), and T1b ICC (5-year RFS: T1b and no necrosis 31.1% vs. T1b and necrosis 11.2% p = 0.006), but was not associated with outcomes among patients with more advanced T2-T3 disease. Patients with T1a ICC and tumor necrosis had similar 5-year RFS as in iduals with T1b ICC and no tumor necrosis (36.1% vs. 31.1% p = 0.66). Tumor necrosis was associated with worse prognosis among patients with T1 ICC. Tumor necrosis for T1 ICC should be considered as an important factor to further stratify outcomes of patients with early T-stage ICC.
Publisher: Wiley
Date: 22-04-2015
DOI: 10.1002/CNCR.29419
Abstract: The impact of postoperative complications on the long-term outcomes of patients undergoing surgery for cancer is unclear. The objective of the current study was to define the incidence of complications among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) and identify the association between morbidity and long-term outcomes. A total of 583 patients undergoing surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. The association between the occurrence and severity of postoperative complications on long-term survival was analyzed. The median age of the patients was 59.9 years and the majority of patients were male (52.3%). A total of 91 patients (15.6%) and 153 patients (26.2%) developed a major and minor postoperative complication, respectively 18 patients (3.5%) died within 90 days of surgery. Median, 1-year, 3-year, and 5-year recurrence-free survival were 10.0 months, 43.3%, 16.7%, and 11.1%, respectively. Postoperative complications (hazard ratio [HR], 1.37, 95% confidence interval [95% CI], 1.08-1.73 [P = .01]) and severity of complications (major vs none: HR, 1.55 95% CI, 1.14-2.11 [P = .01] minor vs none: HR, 1.30 95% CI, 0.99-1.70 [P = .06]) independently predicted shorter recurrence-free survival. Median, 1-year, 3-year, and 5-year overall survival was 27.8 months, 76.8%, 39.0%, and 23.4%, respectively. Postoperative complications (HR, 1.64 95% CI, 1.30-2.08 [P<.001]) and severity of complications (major vs none: HR, 1.79 95% CI, 1.31-2.44 [P<.001] minor vs none: HR, 1.50 95% CI, 1.15-1.95 [P<.01]) independently predicted shorter overall survival. Postoperative complications were found to be independent predictors of worse long-term outcomes. The prevention and management of postoperative complications is crucial to increase both short-term and long-term survival.
Publisher: Elsevier BV
Date: 06-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-01-2020
Publisher: Springer Science and Business Media LLC
Date: 25-07-2017
DOI: 10.1007/S11605-017-3499-6
Abstract: The objective of the current study was to investigate both short- and long-term outcomes of patients undergoing curative-intent resection for intrahepatic cholangiocarcinoma (ICC) stratified by extent of hepatic resection relative to overall final pathological margin status. One thousand twenty-three patients with ICC who underwent curative-intent resection were identified from a multi-institutional database. Demographic, clinicopathological, and operative data, as well as overall (OS) and recurrence-free survival (RFS) were compared among patients undergoing major and minor resection before and after propensity score matching. Overall, 608 (59.4%) patients underwent major hepatectomy, while 415 (40.6%) had a minor resection. Major hepatectomy was more frequently performed among patients who had large, multiple, and bilobar tumors. Roughly half of patients (n = 294, 48.4%) developed a postoperative complication following major hepatectomy versus only one fourth of patients (n = 113, 27.2%) after minor resection (p < 0.001). In the propensity model, patients who underwent major hepatectomy had an equivalent OS and RFS versus patients who had a minor hepatectomy (median OS, 38 vs. 37 months, p = 0.556 and median RFS, 20 vs. 18 months, p = 0.635). Patients undergoing major resection had comparable OS and RFS with wide surgical margin (≥10 and 5-9 mm), but improved RFS when surgical margin was narrow (1-4 mm) versus minor resection in the propensity model. In the Cox regression model, tumor characteristics and surgical margin were independently associated with long-term outcome. Major hepatectomy for ICC was not associated with an overall survival benefit, yet was associated with increased perioperative morbidity. Margin width, rather than the extent of resection, affected long-term outcomes. Radical parenchymal-sparing resection should be advocated if a margin clearance of ≥5 mm can be achieved.
Publisher: Springer Science and Business Media LLC
Date: 06-09-2017
DOI: 10.1007/S00268-017-4199-9
Abstract: We sought to investigate the prognosis of patients following curative-intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV-ICC), hepatolithiasis (Stone-ICC), and no identifiable cause (conventional ICC) etiologic subtype. 986 patients with HBV-ICC (n = 201), stone-ICC (n = 103), and conventional ICC (n = 682) who underwent curative-intent resection were identified from a multi-institutional database. Propensity score matching (PSM) was used to mitigate residual bias. HBV-ICC patients more often had cirrhosis, earlier stage tumors, a mass-forming lesion, well-to-moderate tumor differentiation, and an R0 resection versus stone-ICC or conventional ICC patients. Five-year recurrence-free survival among HBV-ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence-free of only 8.3% among patients with stone-ICC. Similarly, 5-year overall survival among patients with stone-ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV-ICC and conventional ICC, respectively. On PSM, patients with stone-ICC group had equivalent long-term outcomes as HBV-ICC patients. In contrast, on PSM, stone-ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic-only recurrence among patients who had stone-ICC (6.0 months) was worse than OS among HBV-ICC (13.0 months) or conventional ICC (12.0 months) (p = 0.006 and p = 0.082, respectively). While HBV-ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage-for-stage differences in outcomes compared with stone-ICC or conventional ICC. In contrast, patients with stone-ICC had worse long-term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2020
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.HPB.2018.04.005
Abstract: While several prognostic models have been developed to predict long-term outcomes in resectable intrahepatic cholangiocarcinoma (ICC), their prognostic discrimination remains limited. The addition of tumor markers might improve the prognostic power of the classification schemas proposed by the AJCC 8th edition and the Liver Cancer Study Group of Japan (LCSGJ). The prognostic discrimination of the AJCC and the LCSGJ were compared before and after the addition of CA 19-9 and CEA, using Harrell's C-index, net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) in an international, multi-institutional cohort. Eight hundred and five surgically treated patients with ICC that met the inclusion criteria were identified. On multivariable analysis, CEA5 ng/mL, 100IU/mL CA 19-9< 500IU/mL and CA 19-9500 IU/mL were associated with worse overall survival. The C-index of the AJCC and the LCSGJ improved from 0.540 to 0.626 and 0.553 to 0.626, respectively following incorporation of CA 19-9 and CEA. The NRI and IDI metrics confirmed the superiority of the modified AJCC and LCSGJ, compared to the original versions. The inclusion of preoperative CA 19-9 and CEA in the AJCC and LCSGJ staging schemas may improve prognostic discrimination among surgically treated patients with ICC.
Publisher: Wiley
Date: 22-11-2018
DOI: 10.1002/JSO.25305
Abstract: Microvascular invasion (MiVI) is a histological feature of intrahepatic cholangiocarcinoma (ICC) that may be associated with biological behavior. We sought to investigate the impact of MiVI on long-term survival of patients undergoing curative-intent resection for ICC. A total of 1089 patients undergoing curative-intent resection for ICC were identified. Data on clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared among patients with no vascular invasion (NoVI), MiVI, and macrovascular invasion (MaVI). A total of 249 (22.9%) patients had MiVI, while 149 (13.7%) patients had MaVI (±MiVI). MiVI was associated with higher incidence of perineural, biliary and adjacent organ invasion, and satellite lesions (all P < 0.01). On multivariable analysis, MiVI was an independent risk factor of DFS (hazard ratios [HR] 1.5 95%confidence intervals [CI], 1.3-1.9 P 18 months) prognosis. Roughly 1 out of 5 patients with resected ICC had MiVI. MiVI was associated with advanced tumor characteristics and a higher risk of tumor recurrence.
Publisher: Springer Science and Business Media LLC
Date: 10-09-2013
No related grants have been discovered for Hugo Pinto Marques.