Actual 10-Year Survival after Resection of Perihilar Cholangiocarcinoma: What Factors Preclude a Chance for Cure?
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ABSTRACT:
SUBMITTER: van Keulen AM
PROVIDER: S-EPMC8699376 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Partial hepatectomy is a potentially curative therapy for intrahepatic cholangiocarcinoma (ICC). Unfortunately, the overall surgical prognosis remains dismal and the actual 10-year survival has not been reported. This study aimed to document 10-year actual survival rates, identify the prognostic factors associated with 10-year survival rate, and analyze the characteristics of patients who survived ? 10 years. Among 251 patients who underwent curative liver resection for ICC between 2003 and 2006 at the Eastern Hepatobiliary Surgery Hospital, 21 patients (8.4%) survived ? 10 years. The 5-, 7-, and 10-year overall survival rates were 32.3%, 22.3% and 8.4%, respectively. The 10-year cumulative incidence of ICC-related death and recurrence were 80.9% and 85.7%, respectively. Multivariate analysis based on competing risk survival analysis identified that tumor > 5 cm was independently associated with ICC-related death and recurrence (hazard ratios: 1.369 and 1.445, respectively), in addition to carcinoembryonic antigen (CEA) >10 U/mL, carbohydrate antigen 19-9 (CA19-9) >39 U/mL, multiple nodules, vascular invasion, nodal metastasis and local extrahepatic invasion. Patients who survived ? 10 years had a longer time to first recurrence, lower levels of CEA, CA19-9 and alkaline phosphatase, less perioperative blood loss, solitary tumor, smaller tumor size, and absence of nodal metastasis or local extrahepatic invasion. In conclusion, a 10-year survival after liver resection for ICC is possible and can be expected in approximately 8.4% of patients.
| S-EPMC5546499 | biostudies-literature
Project description:BACKGROUND:The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS:A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS:For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS:The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.
| S-EPMC4754626 | biostudies-literature
Project description:BACKGROUND:Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) had the same definition for T2a and T2b. But the value of this classification as prognostic factor remains unclear. METHODS:178 patients with stage T2a or T2b who underwent curative intent resection for pCCA between Jan 2010 and Dec 2018 were enrolled. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate Cox regression analysis. The overall survival (OS) were calculated by Kaplan-Meier method. RESULTS:There was no significant difference in OS between T2a and T2b groups, and the median OS duration were 37 and 31?months (P =?0.354). Both the 7th and 8th edition of the AJCC TNM staging demonstrated a poor prognostic predictive performance. High level of preoperative AST (?85.0?IU/L) and CA19-9 (?1000?U/mL), vascular resection and lower pathological differentiation of the tumor were the independent predictors for poor survival after resection. CONCLUSION:The newly released 8th edition of AJCC staging system demonstrated a poor ability to discriminate the prognosis of patients with stage T2a and T2b pCCA after resection.
| S-EPMC7650292 | biostudies-literature
Project description:Hepatectomy with vascular resection (VR) for perihilar cholangiocarcinoma (PHCC) is a challenging procedure. However, only a few reports on this procedure have been published and its clinical significance has not been fully evaluated. Patients undergoing surgical resection for PHCC from 2002-2017 were studied. The surgical outcomes of VR and non-VR groups were compared. Some 238 patients were included. VR was performed in 85 patients. The resected vessels were hepatic artery alone (31 patients), portal vein alone (37 patients) or both (17 patients). The morbidity rates were almost the same in the VR (49.4 per cent) and non-VR (43.8 per cent) groups (P = 0.404). The mortality rates of VR (3.5 per cent) and non-VR (3.3 per cent) were also comparable (P > 0.999). The median survival time (MST) was 45 months in the non-VR group and 36 months in VR group (P = 0.124). Among patients in whom tumour involvement was suspected on preoperative imaging and whose carbohydrate antigen 19-9 (CA19-9) value was 37 U/ml or less, MST in the VR group was significantly longer than that in the non-VR group (50 versus 34 months, P = 0.017). In contrast, when the CA19-9 value was greater than 37 U/ml, MST of the VR and non-VR groups was comparable (28 versus 29 months, P = 0.520). Hepatectomy with VR for PHCC can be performed in a highly specialized hepatobiliary centre with equivalent short- and long-term outcomes to hepatectomy without VR.
| S-EPMC8342931 | biostudies-literature
Project description:How the side of an extended liver resection impacts the postoperative prognosis of advanced perihilar cholangiocarcinoma (PHC) is still controversial. We compared the outcomes of right (RTS) and left trisectionectomies (LTS) in Bismuth-Corlette (BC) type IV PHC resection. All patients undergoing RTS or LTS for BC type IV PHC in a single tertiary center between January 2012 and December 2019 were compared retrospectively. The endpoints were perioperative outcomes, long-term overall (OS), and disease-free survival (DFS). Among 67 hepatic resections for BC type IV PHC, 25 (37.3%) were LTS and 42 (63.7%) were RTS. Portal vein and artery resection rates were 40% and 52.4% (p = 0.29), and 24% and 0% (p < 0.001) in the LTS and RTS groups, respectively. The severe complication (Clavien-Dindo > IIIa) rate was comparable (36% vs. 21.5%, p = 0.357) while the postoperative liver failure (POLF) rate was lower in the LTS group (16% vs. 38%, p = 0.048). The R0 resection rate was similar between groups (81% vs. 92%; p = 0.154). The five-year OS rate was higher in the LTS group (66% vs. 30%, p = 0.009) while DFS was comparable (43% vs. 18%, p = 0.11). Based on multivariable analysis, the side of the trisectionectomy was an independent predictor of OS. Compared with RTS, LTS is associated with lower POLF and higher overall survival despite more frequent arterial reconstructions in type IV PHC. Although technically more demanding, LTS may be preferred in the treatment of advanced PHC.
| S-EPMC9179267 | biostudies-literature
Project description:BackgroundEarly recurrence after curative resection of perihilar cholangiocarcinoma (PHCC) often occurs within a year of surgery. Preoperative predictors of early recurrence remain unclear. The aim of this study was to define reliable preoperative predictors of early recurrence.MethodsMedical records and preoperative multidetector-row CT of patients with PHCC who underwent resection between 2002 and 2018 were reviewed. Clinical findings, tumour markers, and radiological appearances including a 'periductal enation sign' (PES) where there was evidence of soft tissue enhancement appearing to arise from the extrahepatic bile duct, were analysed.ResultsAmong 261 patients who underwent resection for PHCC, 67 (25.7 per cent) developed early recurrence. Multivariable analysis identified four preoperative risk factors for early recurrence, namely carbohydrate antigen 19-9 (CA19-9) 37 U/ml or higher (OR 2.19, 95 per cent confidence interval (c.i.) 1.08 to 4.46), positive PES (OR 7.37, 95 per cent c.i. 2.46 to 22.10), mass-forming tumour (OR 4.46, 95 per cent c.i. 1.83 to 10.90), and luminal-occlusion tumour (OR 4.52, 95 per cent c.i. 2.11 to 9.68). The OR of preoperative risk factors were used to define four risk subgroups for early recurrence. The early recurrence rates in the low, moderate, high, and very-high risk groups were 0, 9.4 , 39.7, and 65.0 per cent respectively.ConclusionCA19-9, PES, mass-forming tumour, and luminal-occlusion tumour identify patients at higher risk for early recurrence after resection of PHCC.
| S-EPMC9487653 | biostudies-literature
Project description:Perihilar cholangiocarcinoma (PHCC) is one of the most intractable gastrointestinal malignancies. These tumours lie in the core section of the biliary tract. Patients who undergo curative surgery have a 40-50-month median survival time, and a five-year overall survival rate of 35-45%. Therefore, curative intent surgery can lead to long-term survival. PHCC sometimes invades the surrounding tissues, such as the portal vein, hepatic artery, perineural tissues around the hepatic artery, and hepatic parenchyma. Contralateral hepatic artery invasion is classed as T4, which is considered unresectable due to its "locally advanced" nature. Recently, several reports have been published on concomitant hepatic artery resection (HAR) for PHCC. The morbidity and mortality rates in these reports were similar to those non-HAR cases. The five-year survival rate after HAR was 16-38.5%. Alternative procedures for arterial portal shunting and non-vascular reconstruction (HAR) have also been reported. In this paper, we review HAR for PHCC, focusing on its history, diagnosis, procedures, and alternatives. HAR, undertaken by established biliary surgeons in selected patients with PHCC, can be feasible.
| S-EPMC9179358 | biostudies-literature
Project description:ObjectiveTo evaluate the effect of vascular resection (VR), including portal vein resection (PVR) and hepatic artery resection (HAR), on short- and long-term outcomes in patients with perihilar cholangiocarcinoma (PHC).BackgroundResection surgery and transplantation are the main treatment methods for PHC that provide a chance of long-term survival. However, the efficacy and safety of VR, including PVR and HAR, for treating PHC remain controversial.MethodsThis study was registered at the International Prospective Register of Systematic Reviews (CRD42020223330). The EMBASE, PubMed, and Cochrane Library databases were used to search for eligible studies published through November 28, 2020. Studies comparing short- and long-term outcomes between patients who underwent hepatectomy with or without PVR and/or HAR were included. Random- and fixed-effects models were applied to assess the outcomes, including morbidity, mortality, and R0 resection rate, as well as the impact of PVR and HAR on long-term survival.ResultsTwenty-two studies including 4,091 patients were deemed eligible and included in this study. The meta-analysis showed that PVR did not increase the postoperative morbidity rate (odds ratio (OR): 1.03, 95% confidenceinterval (CI): [0.74-1.42], P = 0.88) and slightly increased the postoperative mortality rate (OR: 1.61, 95% CI [1.02-2.54], P = 0.04). HAR did not increase the postoperative morbidity rate (OR: 1.32, 95% CI [0.83-2.11], P = 0.24) and significantly increased the postoperative mortality rate (OR: 4.20, 95% CI [1.88-9.39], P = 0.0005). Neither PVR nor HAR improved the R0 resection rate (OR: 0.70, 95% CI [0.47-1.03], P = 0.07; OR: 0.77, 95% CI [0.37-1.61], P = 0.49, respectively) or long-term survival (OR: 0.52, 95% CI [0.35-0.76], P = 0.0008; OR: 0.43, 95% CI [0.32-0.57], P < 0.00001, respectively).ConclusionsPVR is relatively safe and might benefit certain patients with advanced PHC in terms of long-term survival, but it is not routinely recommended. HAR results in a higher mortality rate and lower overall survival rate, with no proven benefit.
| S-EPMC8466000 | biostudies-literature
Project description:BackgroundPhotodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways).MethodsTo assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm(2)). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo.ResultsPDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic.ConclusionsPDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.
| S-EPMC4691291 | biostudies-literature
Project description: Not available
| S-EPMC9396081 | biostudies-literature