ORCID Profile
0000-0001-7729-2468
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IRCCS Ospedale San Raffaele
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Università Vita Salute San Raffaele
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Publisher: Elsevier BV
Date: 12-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2008
DOI: 10.1002/HEP.22144
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: Oxford University Press (OUP)
Date: 23-03-2007
DOI: 10.1002/BJS.5731
Abstract: It would be desirable to predict which patients are most likely to benefit from preoperative autologous blood donation. This aim of this study was to develop a point scoring system for predicting the need for blood transfusion in liver surgery. The medical records of 480 consecutive patients who underwent hepatic resection were analysed. The data set was split randomly into a derivation set of two-thirds and a validation set of one-third. Univariable analysis was carried out to determine the association between clinicopathological factors and blood transfusion. Significant variables were entered into a multiple logistic regression model, and a transfusion risk score (TRS) was developed. The accuracy of the system was validated by calculating the area under the receiver–operator characteristic (ROC) curve. Factors associated with blood transfusion in multivariable analysis included preoperative haemoglobin concentration below 12·5 g/dl, largest tumour more than 4 cm, need for exposure of the vena cava, need for an associated procedure, and cirrhosis. Each variable was assigned one point, and the total score was compared with the transfusion status of each patient in the validation set. The TRS accurately predicted the likelihood of blood transfusion. In the validation set the area under the ROC curve was 0·89. Use of the TRS could lead to substantial saving by improving the cost-effectiveness of the autologous blood donation programme.
Publisher: Springer Science and Business Media LLC
Date: 26-01-2012
DOI: 10.1007/S00464-012-2147-1
Abstract: Laparoscopy is considered the "gold standard" to perform left-lateral sectionectomy with results identical to those of open surgery, yielding decreased postoperative pain and disability, reduced hospital stay, and shortened patient recovery time. As the emphasis on minimizing the invasiveness of surgical techniques continues, laparoendoscopic single site (LESS) surgery is quickly evolving. The purpose of this study was to compare the results of laparoscopic left-lateral sectionectomy performed using the traditional approach or LESS approach with a case-matched analysis for tumor size, type of resection, and surgical indications. Thirteen patients who underwent LESS left-lateral sectionectomy are considered the study group (LESS group) and compared with 13 patients who underwent left-lateral sectionectomy with traditional laparoscopic approach (conventional group). There were no significant differences between groups for length of surgery (165 min in conventional group vs. 195 min in LESS group), blood loss (150 mL in conventional group vs. 175 mL in LESS group), conversion to open surgery, histological tumor exposure, and requirements of postoperative analgesics. One patient in the LESS group died of cardiac failure due to an unknown severe aortic valve stenosis. No differences were recorded for postoperative complications (23.1% in both groups) and median length of postoperative stay (4 days in both groups). For left-lateral hepatic sectionectomy, LESS surgery is technically feasible and as safe as traditional laparoscopic surgery in terms of intraoperative and postoperative results, even though requiring both hepatobiliary and laparoscopic technique experience.
Publisher: Bentham Science Publishers Ltd.
Date: 02-2008
DOI: 10.2174/138161208783597353
Abstract: Liver ischemia-reperfusion injury occurs in a number of clinical settings, including liver surgery, transplantation, and circulatory shock, leading to significant morbidity and mortality. There is a substantial evidence that hepatic ischemia-reperfusion injury results from an intense inflammatory response initiated by oxidative stress in the liver parenchyma during reperfusion. The anti-inflammatory effects of glucocorticosteroids (GCs) have been known for decades and have found extensive therapeutic use in a wide range of clinical situations associated with organ ischemia. Based on their biological effects, routine perioperative GCs administration has been advocated to reduce hepatic ischemic injury. However, the use of GCs in hepatic surgery remains controversial and clinical benefits are still uncertain. The aim of this review is to present the experimental and clinical evidence about the role of GCs in modulating hepatic ischemia-reperfusion injury.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2007
DOI: 10.1097/SHK.0B013E318063ED11
Abstract: Alterations in hemostatic parameters are a common finding after major hepatic resection. There is growing evidence that inflammation has a significant role in inducing coagulation disarrangement that follows major surgery. To determine whether preoperative methylprednisolone administration has a protective effect against the development of coagulation disorders, we evaluated the effect of preoperative steroids administration on changes in hemostatic parameters and plasma levels of inflammatory cytokines in patients undergoing liver surgery. Seventy-three patients undergoing liver resection were randomized to a steroid group or to a control group. Patients in the steroid group received 500 mg of methylprednisolone preoperatively. Serum levels of coagulation parameters (prothrombin time, platelets, fibrinogen, plasma fibrin degradation products [D-dimer], antithrombin III) and inflammatory mediators (IL-6 and TNF-alpha) were measured before and immediately after the operation and on postoperative days 1, 2, and 5. Multivariate analysis was performed to identify factors related to the characteristics of the patients and surgery affecting coagulation parameters between the two groups. Decreases in antithrombin III, platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products were significantly suppressed by the administration of methylprednisolone. Cytokines production was also significantly suppressed by the administration of methylprednisolone, and there was significant correlation between plasma levels of cytokines and coagulation alterations. These findings suggest that preoperative methylprednisolone administration inhibits the development of coagulation disarrangements in patients undergoing liver resection, possibly through suppressing the production of inflammatory cytokines.
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: 12-2020
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: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2010
DOI: 10.1016/J.JAMCOLLSURG.2009.12.041
Abstract: Traditionally, survival estimates have been reported solely as survival from the time of surgery, but future survival probability likely changes based on the survival time already accumulated after therapy-otherwise known as conditional survival (CS). We sought to assess the comparative performance of various colorectal liver metastasis prognostic scoring systems, as well as to investigate the CS of patients who underwent resection of colorectal liver metastasis. Between 1982 and 2008, 949 patients who underwent colorectal liver metastasis resection were identified from an international multi-institutional database. Various prognostic scoring systems were evaluated using Cox proportional hazards models and calculated concordance index (c). CS estimates were calculated as CS = S((x+5))/S((x)). Overall survival after liver resection was 65% at 3 years and 45% at 5 years, with a median survival of 52 months. All of the prognostic scoring systems had poor-to-moderate prognostic discriminatory ability (Fong c = 0.57, Nordlinger c = 0.56, Memorial Sloan-Kettering Cancer Center nomogram c = 0.58). Using CS, the probability of surviving an additional 5 years, given that the patient had already survived 1, 3, or 5 years, was 41%, 40%, or 50%, respectively. The inadequate performance of the prognostic scoring systems was explained by the fact that as survival from liver resection increased from 0 to 5 years, the 5-year observed CS improved substantially for patients who were initially predicted to have poor survival at the time of surgery. Colorectal liver metastasis prognostic scoring systems have fair-to-moderate performance. CS can provide more accurate prognostic information for patients and physicians after colorectal liver metastasis resection and should be incorporated into the quantification of survival.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
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: 10-03-2009
DOI: 10.1245/S10434-009-0383-Y
Abstract: Hepatocellular carcinoma (HCC) tends to invade the intrahepatic vasculature, especially the portal vein. The presence of portal vein tumor thrombus (PVTT) in patients with HCC is one of the most significant factors for a poor prognosis. The presence of macroscopic PVTT in patients with HCC is also a significant factor for poor prognosis, with a median survival of <3 months without treatment. In surgically resected series, in patients with gross PVTT (PVTT in the portal trunk, its first-order branch, or its second-order branch), the 3-year and 5-year survival rates are reportedly 15% to 28% and 0% to 17%, respectively. The patient was a 77-year-old woman with well-compensated hepatitis C virus-related cirrhosis (stage A6 according to Child-Pugh classification) who sought care at our department for vague abdominal discomfort. Triphasic spiral computed tomographic scan confirmed HCC 6 cm in diameter in the left lobe of the liver. In addition, portal vein tumor thrombosis of the left branch that extended to the right portal vein was present. The procedure included left hepatectomy and en-bloc portal vein thrombectomy with cl ing of both the common portal vein trunk and the right portal vein. The portal vein was incised at the bifurcation of the right and left portal veins, and the thrombus was extracted from the incision in the portal vein. With this procedure, we were able to examine under direct vision the exact extent of the portal vein thrombus, and we identified whether the tumor thrombus was adherent to the venous wall or was freely floating in the venous lumen. Portal cl ing and length of operation were 16 and 330 minutes, respectively. Intraoperative blood loss was 550 mL. The patient was discharged on postoperative day 6, and she was free of disease at 15 months after surgery. Liver resection should be considered a valid therapeutic option for HCC with PVTT.
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: Oxford University Press (OUP)
Date: 16-05-2033
DOI: 10.1002/BJS.6093
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: Elsevier BV
Date: 03-2008
Publisher: Elsevier BV
Date: 07-2023
Publisher: American Medical Association (AMA)
Date: 19-06-2019
Publisher: Elsevier BV
Date: 05-2010
Publisher: Springer Science and Business Media LLC
Date: 14-07-2020
Publisher: Springer Science and Business Media LLC
Date: 07-12-2010
DOI: 10.1245/S10434-010-1459-4
Abstract: Hepatic resection for colorectal liver metastasis (CLM) with concomitant extrahepatic disease (EHD) is a controversial topic. We sought to evaluate the long-term outcome of patients undergoing liver resection for CLM in presence of EHD and identify factors associated with prognosis. From 1996 to 2007, a total of 1629 patients who underwent resection of CLM were identified from an international multi-institutional database. One hundred seventy-one patients (10.4%) underwent resection of EHD. Clinicopathologic and outcome data were collected and analyzed by univariate and multivariate analyses. Median number of treated CLM was 2 (range, 1-18) most patients had solitary EHD (n = 114 66.6%) a single anatomic site of EHD (n = 153 89.4%). The 5-year survival for patients with EHD was 26% compared with 58% for those without EHD (P < 0.001). Recurrence was common (84%). Among patients with EHD, R1 margin status, multiple EHD sites, and location of EHD were associated with worse survival (all P < 0.05). Patients with multiple EHD sites or aortocaval lymph node metastasis had a 5-year survival of 14% and 7%, respectively. When survival was stratified by the total number of metastases treated, the presence of EHD still had a prognostic impact, but the relative impact of EHD diminished as the total number of metastases treated increased. Concurrent resection of hepatic and EHD in well-selected patients may provide the possibility of long-term survival. The risk of recurrence, however, remains high, and a worse outcome is associated with both number of metastases and location of EHD.
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: 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: 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: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2006
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: Wiley
Date: 2008
DOI: 10.1002/JSO.20979
Abstract: Wedge resection (WR) for colorectal liver metastases (CLM) has become more common in an attempt to preserve liver parenchyma. However, some investigator have reported that WR is associated with a higher incidence of positive margin and an inferior survival compared with anatomic resection (AR) 1. This study evaluated survival, margin status, and pattern of recurrence of patients with CLM treated with WR or AR. We identified 208 consecutive patients, in a single institutional database from 1995 to 2004, who underwent either WR or AR. WR was defined as a nonanatomic resection and AR was defined as single resection of one or two liver segments. Patients with combined WR-AR and patients requiring resection of more than two segments or radiofrequency ablation were excluded from the analysis. One hundred six patients underwent WR and 102 patients had AR. There were no differences in the rate of positive surgical margin (P = 0.146), overall recurrence rates (P = 0.211), and patterns of recurrence between the two groups (P = 0.468). The median survival was 32 months for WR and 42 for AR, with 5-year survival rates of 29% and 27% respectively, with no significant difference (P = 0.308). Morbidity was similar between the two groups. WR is a safe procedure and does not disadvantage the patients in terms of tumor recurrence and overall survival.
Publisher: Springer Science and Business Media LLC
Date: 10-2009
DOI: 10.1007/S11605-009-1050-0
Abstract: Although 5-year survival approaches 55% following resection of colorectal liver metastasis, most patients develop recurrent disease that is often isolated to the liver. Although repeat curative intent surgery (CIS) is increasingly performed for recurrent colorectal liver metastasis, only small series have been reported. We sought to determine safety and efficacy of repeat CIS for recurrent colorectal liver metastasis as well as determine factors predictive of survival in a large multicenter cohort of patients. Between 1982 and 2008, 1,706 patients who underwent CIS--defined as curative intent hepatic resection/radiofrequency ablation (RFA)--for colorectal liver metastasis were identified from an international multi-institutional database. Two hundred forty-six (14.4%) patients underwent 301 repeat CIS. Data on clinico-pathologic factors, morbidity, and mortality were collected and analyzed. Following initial CIS, 645 (37.8%) patients had recurrence within the liver. Of these, 246 patients underwent repeat CIS for recurrent disease. The majority had hepatic resection alone as initial therapy (n = 219 89.0%). A subset of patients underwent third (n = 46) or fourth (n = 9) repeat CIS. Mean interval between surgeries was similar (first --> second, 19.1 months second --> third, 21.5 months third --> fourth, 11.3 months P = 0.20). Extent of hepatic resection decreased with subsequent CIS (>or=hemihepatectomy: first CIS, 30.9% versus second CIS, 21.1% versus third/fourth CIS, 16.4% P = 0.004). RFA was utilized in one quarter of patients undergoing repeat CIS (second CIS, 21.1% versus third/fourth CIS, 25.5%). Mortality and morbidity were similar following second, third, and fourth CIS, respectively (all P > 0.05). Five-year survival was 47.1%, 32.6%, and 23.8% following the first, second, and third CIS, respectively. Presence of extra-hepatic disease was predictive of worse survival (HR = 2.26, P = 0.01). Repeat CIS for recurrent colorectal liver metastasis can be performed with low morbidity and near-zero mortality. Patients with no extra-hepatic disease are best candidates for repeat CIS. In these patients, repeat CIS can offer the chance of long-term survival.
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: Springer Science and Business Media LLC
Date: 12-07-2008
DOI: 10.1007/S00464-008-0022-X
Abstract: Previous comparative studies have demonstrated that laparoscopic liver resection is associated with more frequent use and longer duration of portal c ing than open liver resection, a fact that may partially explain the improvement in operative blood loss reported by most series of laparoscopic liver resection. The aim of this prospective study was to evaluate the real need for portal cl ing in laparoscopic liver surgery. Surgical outcomes of 40 consecutive patients who underwent laparoscopic liver resection for benign and malignant lesions from September 2005 to August 2007 were evaluate. Portal cl ing was not systematically used. No patient required blood transfusion and median blood loss was 160 ml (range 100-340 ml). Mean operating time was 267 min (range 220-370 min) and portal cl ing was necessary in only one patient. Surgical complications included two grade I complication, three grade II, and one case of postoperative hemorrhage (grade III). Laparoscopic liver surgery without cl ing can be performed safely with low blood loss.
Publisher: American Medical Association (AMA)
Date: 2012
DOI: 10.1001/ARCHSURG.2011.771
Abstract: To evaluate improvements in operative and long-term results following surgery for hilar cholangiocarcinoma. Retrospective multicenter study including 17 Italian hepatobiliary surgery units. A total of 440 patients who underwent resection for hilar cholangiocarcinoma from January 1, 1992, through December 31, 2007. Postoperative mortality, morbidity, overall survival, and disease-free survival. Postoperative mortality and morbidity after liver resection were 10.1% and 47.6%, respectively. At multivariate logistic regression, extent of resection (right or right extended hepatectomy) and intraoperative blood transfusion were independent predictors of postoperative mortality (P = .03 and P = .006, respectively) in patients with jaundice, mortality was also higher without preoperative biliary drainage than with biliary drainage (14.3% vs 10.7%). During the study period, there was an increasingly aggressive approach, with more frequent caudate lobectomies, vascular resections, and resections for advanced tumors (T stage of 3 or greater and tumors with poor differentiation). Despite the aggressive approach, the blood transfusion rate decreased from 81.0% to 53.2%, and mortality slightly decreased from 13.6% to 10.8%. Median overall survival significantly increased from 16 to 30 months (P = .05). At multivariate analysis, R1 resection, lymph node metastases, and T stage of 3 or greater independently predicted overall and disease-free survival. Surgery for hilar cholangiocarcinoma has improved with decreased operative risk despite a more aggressive surgical policy. Long-term survival after liver resection has also increased, despite the inclusion of cases with more advanced hilar cholangiocarcinoma. Preoperative biliary drainage was a safe strategy before right or right extended hepatectomy in patients with jaundice. Pathologic factors independently predicted overall and disease-free survival at multivariate analysis.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2007
DOI: 10.1007/S11605-007-0244-6
Abstract: Left lateral sectionectomy is one of the most commonly performed laparoscopic liver resections, but limited clinical data are actually available to support the advantage of laparoscopic versus open-liver surgery. The present study compared the short-term outcomes of laparoscopic versus open surgery in a case-matched analysis. Surgical outcome of 20 patients who underwent left lateral sectionectomy by laparoscopic approach (LHR group) from September 2005 to January 2007 were compared in a case-control analysis with those of 20 patients who underwent open left lateral sectionectomy (OHR group). Both groups were similar for: tumor size, preoperative laboratory data, presence of cirrhosis, and histology of the lesion. Surgical procedures were performed in both groups combining the ultrasonic dissector and the ultrasonic coagulating cutter without portal cl ing. Compared with OHR, the LHR group had a decreased blood loss (165 mL versus 214 mL, P=0.001), and earlier postoperative recovery (4.5 versus 5.8 days, P=0.003). There were no significant differences in terms of surgical margin and operative time. Morbidity was comparable between the two groups, but two cases of postoperative ascites were recorded in two cirrhotic patients in the OHR. Major complications were not observed in either groups. Laparoscopic resection results in reduced operative blood loss and earlier recovery with oncologic clearance and operative time comparable with open surgery. Laparoscopic liver surgery may be considered the approach of choice for tumors located in the left hepatic lobe.
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: Ovid Technologies (Wolters Kluwer Health)
Date: 14-01-2020
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: Elsevier BV
Date: 06-2007
Publisher: Springer Science and Business Media LLC
Date: 17-06-2011
DOI: 10.1245/S10434-011-1832-Y
Abstract: Management of patients with neuroendocrine liver metastasis (NELM) remains controversial. We sought to examine the relative efficacy of surgical management versus intra-arterial therapy (IAT) for NELM and determine factors predictive of survival. A total of 753 patients who had surgery (n = 339) or IAT (n = 414) for NELM from 1985 to 2010 were identified from nine hepatobiliary centers. Clinicopathologic data were assessed with regression modeling and propensity score matching. Most patients had a pancreatic (32%) or a small bowel (27%) primary tumor 47% had a hormonally active tumor. There were statistically significant differences in characteristics between surgery versus IAT groups (hormonally active tumors: 28 vs. 48% hepatic tumor burden >25%: 52% vs. 76%) (all P < 0.001). Among surgical patients, most underwent hepatic resection alone without ablation (78%). The median number of IAT treatments was 1 (range, 1-4). Median and 5-year survival of patients treated with surgery was 123 months and 74% vs. 34 months and 30% for IAT (P 25% hepatic tumor involvement, there was no difference in long-term outcome after surgery versus IAT among asymptomatic patients (P = 0.78). Asymptomatic patients with a large (>25%) burden of liver disease benefited least from surgical management and IAT may be a more appropriate treatment strategy. Surgical management of NELM should be reserved for patients with low-volume disease or for those patients with symptomatic high-volume disease.
Publisher: Wiley
Date: 04-2010
DOI: 10.1002/JSO.21541
Abstract: Laparoscopy is gaining acceptance as a safe procedure for resection of liver neoplasms. The aim of this study is to evaluate surgical results and mid-term survival of minor hepatic resection performed for HCC. Data of 16 patients with HCC, undergoing laparoscopic hepatectomy from September 2005 to January 2009, were compared to a control group of 16 patients who underwent open resection (OR) during the same period. The two groups were matched in terms of type of resection, tumor size, and severity of cirrhosis. One patient underwent conversion to an open approach. Laparoscopic approach resulted in shorter operating time (150 min, P:0.044) and lower blood loss (258 ml, P:0.008). There was no difference in perioperative morbidity and mortality rate laparoscopic approach was associated with a shorter hospital stay (6.3 days, P:0.039). After a mean follow up of 32 months, disease free survival and overall survival were 40.2 and 23.3 months for laparoscopic group, and 47.7 and 31.4 months for OR group (P NS). Laparoscopic resection of HCC is feasible and safe in selected patients and can result in good surgical results, with similar outcomes in terms of overall and disease-free survival.
Publisher: Springer Science and Business Media LLC
Date: 10-09-2013
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: 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: Springer Science and Business Media LLC
Date: 20-11-2007
DOI: 10.1007/S00268-007-9285-Y
Abstract: The aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases. The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal cl ing use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). The univariate analysis revealed a significant difference (p 5 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 months, MSKCC-CRS >2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA >5 ng/ml, and high MSKCC-CRS. No single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3-G4 differentiation, preoperative CEA >5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery.
Publisher: Springer Science and Business Media LLC
Date: 29-03-2008
DOI: 10.1245/S10434-008-9882-5
Abstract: Although hepatic artery infusion chemotherapy (HAIC) of floxuridine (FUDR) for colorectal liver metastases (CLM) can produce high response rates, data concerning preoperative HAIC are scarce. The aim of this study was to assess the feasibility and results of liver resection after preoperative HAIC with FUDR. Between 1995 and 2004, 239 patients with isolated CLM received HAIC in our institution. Fifty of these patients underwent subsequent curative liver resection (HAIC group). Short- and long-term results of the HAIC group were compared with the outcomes of 50 patients who underwent liver resection for CLM without preoperative chemotherapy. Postoperative morbidity rate were comparable between the two groups. Overall disease-free survival at 1 and 3 years after hepatectomy were 77.5% and 57.5% in the HAIC group and 62.9% and 37% in the control group (P = .036). Overall survival from diagnosis of CLM at 1, 3, and 5 years were 97%, 59%, and 49% in the HAIC group versus 94%, 48%, and 35% in the control group (P = .097). When patients were stratified according to clinical-risk scoring (CRS) system, patients with more advanced disease at the time of liver resection (CRS > or = 3) had a median survival of 41 months in the HAIC group (n = 37) and 35 months in the control group (n = 34) (P = .031). HAIC of FUDR does not negatively affect the outcome of subsequent liver resection. Preoperative HAIC of FUDR may reduce liver recurrence rate and improve long-term survival in patients with more advanced liver disease.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.AMJSURG.2007.02.022
Abstract: Parenchymal liver transection represents a fundamental phase of liver surgery. Several devices have been described for safe and careful dissection of the liver parenchyma during laparoscopic liver surgery, but the ideal technique has not yet been defined. This report describes the combined use of ultrasonic dissector and the ultrasonic coagulating cutter for laparoscopic liver resection. The ultrasonic dissector is used to fracture the parenchyma along the line of proposed ision, and the uncovered bridging structures are sealed using the ultrasonic coagulating cutter. The combined use of ultrasonic dissector and harmonic scalpel allows liver resection to be safely performed, with the advantage of minimal surgical complication and low blood losses.
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: 24-06-2014
DOI: 10.1002/JSO.23671
Abstract: An inadequate volume of future liver remnant (FLR) remains an absolute contraindication to liver resection. FLR measurement correlates with surgical outcome and is fundamental to identify those patients that may benefit from portal vein embolization (PVE) and to assess the liver volume change following embolization. In order to minimize the risk of postoperative liver failure, preoperative analysis of FLR must be included in the surgical planning of every major liver resection. The aims of this review are to describe the use of preoperative volumetric analysis in modern liver surgery and indications for PVE.
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: 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: Ovid Technologies (Wolters Kluwer Health)
Date: 2006
DOI: 10.1002/LT.20745
Abstract: Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response.
Publisher: Wiley
Date: 02-10-2015
DOI: 10.1111/HEPR.12585
Abstract: Besides the residual liver volume, damage of the microcirculation secondary to increased portal blood flow is a main determinant of postoperative liver failure (PLF). Endothelin-1 (ET-1), produced by sinusoidal endothelial cells, plays a key role in the regulation of hepatic microcirculation. The aim of this study was to determine whether ET-1 levels has any prognostic utility in predicting PLF. Patients undergoing liver resection for primary or secondary liver tumors at San Raffaele Hospital, Milan, were prospectively enrolled in the study. Serial postoperative serum ET-1 levels in patients undergoing liver resections were correlated with indices of inflammatory response, liver failure and death. A total of 144 patients were included. ET-1 levels in patients who underwent major or extended liver resection were significantly higher than in patients who had a minor resection on postoperative day (POD) 1 (P = 0.003), POD 2 (P = 0.0001) and POD 5 (P = 0.0001). Eight patients developed PLF and ET-1 was significantly higher compared with patients without PLF on POD 2 (P = 0.002) and POD5 (P = 0.006). Serum ET-1 concentration on POD 2 was an independent predictor of PLF in multivariate analysis. ET-1 is as an early index of PLF and provides a rationale for therapeutic manipulation, with many potential clinical implications to prevent PLF onset and reduce its severity.
Publisher: Springer Science and Business Media LLC
Date: 09-07-2011
DOI: 10.1245/S10434-011-1902-1
Abstract: For patients with colorectal liver metastasis (CLM), the presence of concomitant perihepatic ara-aortic lymph node metastasis (LNM) is considered a contraindication to liver resection. We sought to determine the benefits of liver resection among patients with CLM + LNM by examining long-term outcomes among a large cohort of patients. Between October 1996 and December 2007, 61 patients with CLM and pathologically proven LNM were identified from an international multi-institutional database of 1629 patients. The effect of LNM, as well as other prognostic factors, on recurrence-free and overall survival was analyzed. Median overall survival was 32 months, and 1-, 3-, and 5-year overall survival were 86, 35, and 18%, respectively. Five patients were alive and disease-free at last follow-up. Survival was associated with location of LNM. Specifically, 5-year overall survival was 30% among patients with LNM along the hepatoduodenal ligament/retropancreatic area (area 1), 14% among patients with LNM along the common hepatic artery/celiac axis (area 2), and there was only one long-term survivor who experienced recurrent disease among patients who had CLM + para-aortic LNM (area 3) (P = 0.004). On multivariate analyses, overall margin status (hazard ratio [HR] = 2.0), treated number of metastases >6 (HR = 2.3) and para-aortic lymph node involvement (HR = 2.6) each remained significantly associated with increased risk of death (all P < 0.05). Although overall survival in the setting of LNM is only 18%, certain subsets of patients with LNM can benefit from surgical resection. Specifically, patients with CLM + LNM isolated to area 1 had a 5-year survival of approximately 30%, while long-term survival among patients with para-aortic LNM was rare.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2020
Publisher: Elsevier BV
Date: 08-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2010
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.GASSUR.2006.02.002
Abstract: We evaluated the feasibility and effectiveness of combining two different electronic devices, the ultrasonic dissector (UD) and the harmonic scalpel (HS), during hepatic resection. One hundred consecutive patients underwent liver resection using UD plus HS between January and December 2004 (UD + HS group). The ultrasonic dissector was used to fracture liver parenchyma and the uncovered vessel was sealed using the HS. Surgical outcomes were compared with 100 consecutive patients who underwent liver resection using the cl crushing method. Operative variables, postoperative liver function, hospital stay, and type and number of complications were compared. The two groups were equivalent in term of demographic and pathologic variables. The UD + HS group had a decreased blood loss (500 ml versus 700 ml, P = 0.005), number of patients transfused (22 versus 39, P = 0.009), tumor exposure at the transection surface (4 versus 12, P = 00.012), and hospital stay (7 versus 8.5 days, P = 0.020). Postoperative major complications, in particular, fluid collection and biliary fistula, were significantly less frequent in the UD + HS group (2 versus 9, P = 0.030). A longer operative time was recorded in the UD + HS group (385 versus 330 minutes, P = 0.001). The combined use of UD with HS allows liver resection to be safely performed, with the advantage of reducing blood losses and surgery-related complications. The only major disadvantage may be a longer transection time.
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: Wiley
Date: 05-09-2012
DOI: 10.1002/JSO.23260
Abstract: The presence of extra-hepatic disease (EHD) is no longer an absolute contraindication to surgery in patients with colorectal liver metastases (CRLM). Recently, a novel prognostic model predicting overall survival in such patients was proposed using five risk factors (EHD other than isolated lung metastases, CEA ≥10 ng/ml, >5 liver metastases, right colon as the primary CRC location, and diagnosis of EHD concomitant to CRLM recurrence). A bi-institutional database was used to perform an external validation of this model. Ninety-seven patients operated for CRLM and EHD between 1982 and 2011 in two institutions was analyzed. The proposed prognostic model was validated in this cohort using Cox proportional hazards models and the concordance index (c). Of the five proposed risk factors, only EHD other than isolated lung metastases was found to independently predict overall survival [Hazards Ratio (HR) = 2.10 (95% CI: 1.01-4.40)]. Although, the number of risk factors was marginally associated with overall survival in univariate analysis (P = 0.049), the performance of the proposed prognostic model was poor when applied to our cohort (c = 0.64). The examined prognostic model of survival in patients with CRLM and EHD had poor performance. Further research is warranted to delineate the subset of patients who will benefit from surgery.
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: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2012
DOI: 10.1016/J.JAMCOLLSURG.2012.04.013
Abstract: The best treatment for patients with small hepatocellular carcinoma (S-HCC) is still controversial. The aim of this study was to evaluate operative and long-term results after liver resection (LR) for S-HCC, defined as tumor ≤3 cm. Retrospective multicenter study of 588 LRs for S-HCC from 8 Italian hepatobiliary surgery units (years 1992 to 2008). Primary outcomes included operative risk. Logistic regression analysis was used to evaluate risk factors for postoperative mortality. Secondary outcomes were overall survival (OS) and disease-free survival (DFS), estimated by the Kaplan-Meier method. Postoperative mortality was 1.9%, morbidity was 35.7% (major morbidity 7.3%), and blood transfusion rate was 13.8%. Child-Pugh class B and blood transfusions were associated with higher postoperative mortality. Rates of microvascular invasion and microsatellite nodules were 37.0% and 23.1%. After a median follow-up of 38.4 months, 5- and 10-year OS rates were 52.8% and 20.3%, with DFS of 32.4% and 21.7%. Local recurrence rate was 1.4%. Between the years 2000 and 2008, 5-year OS was significantly higher than that between the years 1992 and 1999 (61.9% vs 42.6% p < 0.001). In multivariable analysis, Child-Pugh class B, portal hypertension, and microsatellite lesions were independently associated with poor OS. Microsatellite lesion was the only variable independently associated with poor DFS. Liver resection for S-HCC has improved over the years, with decreased operative risk. Long-term survival after LR has increased. Despite small tumor size, rates of microsatellite nodules and microvascular invasion are not negligible. Presence of microsatellite lesions was the only variable identified as being associated with poor both OS and DFS.
Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/JCS.248849
Abstract: A mother's ability to produce a nutritionally-complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by mammary epithelial cells is adaptive, its release is exquisitely-timed and its own glandular stagnation with the permanent cessation of suckling triggers the cell death and tissue remodeling that enables female mammals to nurse successive progeny. Both chemical and mechanical signals play a role in this process. Despite this duality of input, however, much remains unknown about the nature and function of mechanical forces in this organ. Here, we characterize the force landscape in the functionally-mature gland and the capacity of luminal and basal cells to experience and exert force. We explore molecular instruments for force-sensing, in particular channel-mediated mechanotransduction, revealing increased expression of Piezo1 in mammary tissue in lactation and confirming functional expression in luminal cells. We also reveal, however, that lactation and involution proceed normally in mice with luminal-specific Piezo1 deletion. These findings support a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.
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: 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: 14-04-2005
DOI: 10.1007/S00125-005-1725-3
Abstract: Efficient islet isolation is an important prerequisite for successful clinical islet transplantation. Although progressively improved, islet yield and quality are, however, unpredictable and variable and require standardisation. Since 1989 we have processed 437 pancreases using the automated method. The donor characteristics, pancreas procurement, and digestion and purification procedures including a wide enzyme characterisation of these pancreases were analysed and correlated with islet yield and transplant outcome. By univariate analysis, islet yield was significantly associated with donor age (r=0.16 p=0.0009), BMI (r=0.19 p=0.0004), good pancreas condition (p=0.0031) and weight (r=0.15 p=0.0056), total collagenase activity (r=0.22 p=0.0001), adjusted collagenase activity/mg (r=0.18 p=0.0002), collagenase activity/solution volume (r=0.18 p=0.0002) and neutral protease activity/solution volume (r=0.14 p=0.0029). A statistically significant contribution to the variability of islet yield in a multivariate analysis performed on donor variables was found for donor BMI (p=0.0008). In a multivariate analysis performed on pancreas variables a contribution was found for pancreas weight (p=0.0064), and for a multivariate analysis performed on digestion variables we found a contribution for digestion time (p=0.0048) and total collagenase activity (p=0.0001). Twenty-four patients with type 1 diabetes received single islet preparations from single donors. In these patients, multivariate analyses showed that the reduction in insulin requirement was significantly associated with morphological aspects of islets (p=0.0010) and that 1-month C-peptide values were associated with islet purity (p=0.0071). These data provide baseline donor, digestion and purification selection criteria for islet isolation using the automated method and indicate that the morphological aspect may be a clinically relevant measure of islets on which the decision for transplant can be based.
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: 02-09-2008
Abstract: Laparoscopic liver resection (LLR) represents a natural extension of minimally invasive surgery. Several case-control studies have demonstrated that LLR is safe and feasible in carefully selected patients. LLR is associated with reduced operative blood loss and earlier recovery when compared with open surgery. In addition, oncologic clearance achieved with LLR is comparable to that achieved with open surgery. Improved cosmesis and postoperative patient comfort also argue in favor of LLR compared with open surgery. When considering whether a patient is suitable for LLR, the size and location of the neoplasm must be taken into account. Operator experience must also be considered as LLR is technically demanding and requires experience in conventional hepatobiliary surgery and advanced laparoscopy. The main indication for LLR is limited resection of superficial or peripherally located tumors. In the case of malignant tumors, LLR should be indicated only if a safe and effective oncologic resection can be performed, and the availability of laparoscopy should not change the indications for benign lesions. Ultimately, the future application of LLR will depend on how easily liver surgeons can master the technique and whether the long-term results of LLR can match those achieved with open resection.
Publisher: Oxford University Press (OUP)
Date: 24-03-2021
DOI: 10.1093/BJS/ZNAB101
Abstract: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351 best case 196, worst case 816) or non-cancer surgery (733 best case 407, worst case 1664). Both exceeded the NNV in the general population (1840 best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
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: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.HEPRES.2006.05.006
Abstract: Based on previous studies in experimental models, pro-inflammatory Th1 cytokines (i.e. TNF-alpha and IFN-gamma) are thought to play a pathogenic role in hepatic ischemia/reperfusion injury, while anti-inflammatory Th2 cytokines (i.e. IL-4 and IL-10) have been associated with reduced liver disease severity. To test the relevance of these concepts in humans, cytokine expression profiles were characterized in liver biopsies from patients undergoing hepatic resection following intermittent portal cl ing. Twelve patients were analyzed for the intrahepatic expression of TNF-alpha, IFN-gamma, IL-4 and IL-10 before and about 90min after the last reperfusion. In addition, parameters of liver damage including sALT and serum levels of TNF-alpha were analyzed at 2, 24 and 48h after surgery. When compared with pre-reperfusion liver specimens, all post-reperfusion biopsies showed significantly increased levels of TNF-alpha and IFN-gamma mRNAs. Conversely IL-4 and IL-10 mRNA levels were significantly increased in only seven patients. A negative correlation was observed between Th2 cytokines (IL-4, IL-10) and ALT and serum levels of TNF-alpha. Furthermore, the presence of hepatic steatosis was significantly associated with lower intrahepatic contents of IL-4 and IL-10. The results suggest that the local early expression of Th2 cytokines may contribute to attenuate liver injury following ischemia reperfusion in humans. The early imbalance between pro- and anti-inflammatory cytokines seen in steatotic liver subjected to I/R could explain, at least partially, the decreased tolerance of steatotic livers to I/R injury.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2020
Publisher: Elsevier BV
Date: 08-2009
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: MDPI AG
Date: 03-07-2020
Abstract: The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a ‘toolbox’ of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.
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: Elsevier BV
Date: 08-2012
Publisher: Royal College of Surgeons of England
Date: 07-2006
Abstract: The aim of this study was to assess the safety and the efficacy of hepatic resective surgery in the treatment of single lobe hepatolithiasis. Retrospective analysis and comparison between hepatic resections in patients with hepatolithiasis (hepatolithiasis group [HG]) and liver masses (control group [CG]). Seventeen consecutive Caucasian patients with single lobe hepatolithiasis (HG) and 30 patients with liver masses without chronic liver disease and previous chemotherapy (CG), were operated during the 5-year period 2000–2005, inclusive. Major hepatic resections including 4 right hepatectomies, 10 left hepatectomies, and 3 left lateral sectionectomy in HG, and 12 right hepatectomies, 3 extended right hepatectomy, 5 left hepatectomies, 4 left lateral sectionectomy, 5 bisegmentectomy, and 1 mesohepatectomy in CG. The main outcome measures were: type and length of surgical procedures, intra- and postoperative blood losses and transfusions (packed red blood cells [PRBC] and fresh frozen plasma [FFP]), intra- and postoperative course and complications (within 30 days of the operation), length of hospitalisation, histopathology, and recurrence of hepatolithiasis. Mean operation time was 6.21 ± 2.38 h in HG versus 7.10 ± 2.21 h in CG (P = 0.33). Mean intra-operative blood loss in CG was higher than in HG (1010 ± 550 ml versus 560 ± 459 ml P = 0.035). The other variables considered in the two groups were not statistically different. Intra-operative transfusion were 0.50 ± 0.85 units in HG versus 1.35 ± 2.25 units of PRBC in CG (P = 0.06), and 0.66 ± 1.34 units in HG versus 0.68 ± 1.20 units of FFP in CG (P = 0.44), respectively. No cases of death were registered. Postoperative complications occurred in 12 patients (25.5%) – 5 cases (10.6%) in HG and 7 cases (14.8%) in CG (P = 0.18). Mean postoperative transfusions were 0.47 ± 1.24 units in HG versus 1.10 ± 1.18 units of PRBC in CG (P = 0.35), and 0.65 ± 1.40 units in HG versus 0.46 ± 0.82 units of FFP in CG (P = 0.25), respectively. Difference in median hospitalisation was not statistically significant (14 ± 10 days versus 12 ± 9 days P = 0.28). Histopathology showed cholangiocarcinoma in 2 cases (11.7%). During the follow-up period (range, 5–127 months mean, 50.4 ± 41.9 months), 1 patient had lithiasis recurrence and 1 patient died for the co-existing cholangiocarcinoma. Hepatic resection is the treatment of choice in patients with single lobe hepatolithiasis. An early indication for surgery may reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.
Publisher: Elsevier BV
Date: 06-2013
Publisher: American Medical Association (AMA)
Date: 09-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2007
DOI: 10.1002/LT.21371
Publisher: Springer Science and Business Media LLC
Date: 29-06-2010
DOI: 10.1245/S10434-010-1154-5
Abstract: Management of neuroendocrine tumor liver metastasis (NELM) remains controversial, with some advocating an aggressive surgical approach while others have adopted a more conservative strategy. We sought to define the efficacy of the surgical management of NELM in a large multicenter international cohort of patients. We identified 339 patients who underwent surgical management for NELM from 1985 to 2009 from an international database of eight major hepatobiliary centers. Relevant clinicopathologic data were assessed using Kaplan-Meier and Cox regression models. Most patients had a pancreatic (40%) or small bowel (25%) neuroendocrine tumor (NET) primary. The majority of patients (60%) had bilateral liver disease. At surgery, 78% of patients underwent hepatic resection, 3% ablation alone, and 19% resection + ablation. Major hepatectomy was performed in 45% of patients, and 14% underwent a second liver operation. Carcinoid was the most common NET histological subtype (53%). Median survival was 125 months, with overall 5- and 10-year survival of 74%, and 51%, respectively. Disease recurred in 94% of patients at 5 years. Patients with hormonally functional NET who had R0/R1 resection benefited the most from surgery (P = 0.01). On multivariate analyses, synchronous disease [hazard ratio (HR) = 1.9], nonfunctional NET hormonal status (HR = 2.0), and extrahepatic disease (HR = 3.0) remained predictive of worse survival (all P < 0.05). Liver-directed surgery for NELM is associated with prolonged survival however, the majority of patients will develop recurrent disease. Patients with hormonally functional hepatic metastasis without prior extrahepatic or synchronous disease derive the greatest survival benefit from surgical management.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2020
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: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2009
Publisher: Springer Science and Business Media LLC
Date: 14-06-2008
DOI: 10.1007/S00423-008-0349-8
Abstract: Laparoscopic surgery has gained growing acceptance, but this does not hold for laparoscopic surgery of the liver, above all for patients with hepatocellular carcinoma (HCC) and cirrhosis. This approach mainly includes diagnostic procedures and interstitial therapies. However, we believe there is room for laparoscopic liver resections in well-selected cases. The aim of this study is to assess: (a) the risk of intraoperative bleeding and postoperative complications, (b) the safety and the respect of oncological criteria, and (c) the potential benefit of laparoscopic ultrasound in guiding liver resection. A prospective study of laparoscopic liver resections for hepatocellular carcinoma was undertaken in patients with compensated cirrhosis. Hepatic involvement had to be limited and located in the left or peripheral right segments (segments 2-6), and the tumor had to be 5 cm or smaller. Tumor location and its transection margins were defined by laparoscopic ultrasound. From January 1997, 22 out of 250 patients with HCC (9%) underwent laparoscopic liver resections. The mean patient age was 61.4 years (range, 50-79 years). In three patients, conversion to laparotomy was necessary. The laparoscopic resections included five bisegmentectoies (2 and 3), nine segmentectomies, two subsegmentectomies and three nonanatomical resections for extrahepatic growing lesions. The mean operative time, including laparoscopic ultrasonography, was 199 +/- 69 min (median, 220 range, 80-300). Perioperative blood loss was 183 +/- 72 ml (median, 160 range, 80-400 ml). There was no mortality. Postoperative complications occurred in two out of 19 patients: an abdominal wall hematoma occurred in one patient and a bleeding from a trocar access in the other patient requiring a laparoscopic re-exploration. Mean hospital stay of the whole series was 6.5 +/- 4.3 days (median, 5 range, 4-25), while the mean hospital stay of the 19 laparoscopic patients was 5.4 +/- 1 (median, 5 range, 4-8). Laparoscopic treatment should be considered in selected patients with HCC and liver cirrhosis in the left lobe or segments 5 and 6 of the liver. It is clear that certain types of laparoscopic resection are feasible and safe when carried out by adequately skilled surgeons with appropriate instruments.
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.
Location: Italy
No related grants have been discovered for Luca Antonio Aldrighetti.