Resection Of Cholangiocarcinoma Research Articles

Les progrès dans la prise en charge des cholangiocarcinomes

Cancers of the bile ducts or cholangiocarcinomas are a rare entity whose incidence is increasing in France. Surgical resection of cholangiocarcinoma remains the only curative therapy. Adjuvant therapy with capecitabine at a fixed dose of 1250mg/m2 twice daily from day 1 to day 14 (21-day cycle) for a 6 months period is now the standard of care after curative surgery. At a metastatic stage, the reference treatment consists of the combination of a platinum salt in addition to gemcitabine. No biomarker has been identified to predict the response to chemotherapy. DNA sequencing of the tumor can identify specific tumor mutations in bile duct cancers that are the focus of targeted studies.

Chemoradiotherapy for Initially Unresectable Locally Advanced Cholangiocarcinoma

Surgical resection is the only available treatment for achieving long-term survival in cholangiocarcinoma. The purpose of this study is to elucidate the utility of chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. Unresectable locally advanced cholangiocarcinoma was defined as those in which radical surgery could not be achieved even with aggressive surgical procedure. Fifteen candidates (7 intrahepatic cholangiocarcinomas and 8 hilar cholangiocarcinomas) underwent chemoradiotherapy. Fourteen of the 15 patients received oral S-1 chemotherapy. Radiotherapy was administered with 50Gy for each patient. After chemoradiotherapy, the resectability of each cholangiocarcinoma was reexamined. Of the 15 patients with initially unresectable locally advanced cholangiocarcinoma, 11 (73.3%) were judged to have resectable cholangiocarcinoma after chemoradiotherapy, and received radical hepatectomy (R0 resection in 9 patients). Among the 11 patients who underwent surgical resection, 4 had recurrence-free survival and the median survival time (MST) was 37months. The overall 1-, 2-, and 5-year survival rates were 80.8, 70.7 and 23.6%, respectively. Among the 4 patients who were unable to receive surgery, 3 died of the primary disease and the MST was 10months. The overall 1- and 2-year survival rates were 37.5 and 0%, respectively. Patients who received radical surgery had significantly longer survival time than those who were unable to receive surgery (p = 0.027). Chemoradiotherapy allowed patients with initially unresectable locally advanced cholangiocarcinomas to be reclassified as surgical candidates in a substantial proportion. Chemoradiotherapy might be one of the treatment options for similarly advanced cholangiocarcinomas.

Preoperative biliary stenting is associated with increased complications after liver resection for cholangiocarcinoma

Background: Biliary stenting prior to liver resection for hilar and intrahepatic cholangiocarcinoma is common. While preoperative stenting in pancreatic surgery has been associated with increased infectious complications, its effects after liver resection have yet to be examined. Methods: Patients undergoing liver resection for hilar and intrahepatic cholangiocarcinoma were analyzed using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Associations between preoperative stenting (percutaneous or endoscopic) and 30-day outcomes were evaluated. Results: Of the 598 liver resections performed between 2014 and 2015, 161 (27.3%) underwent preoperative biliary stenting. Stented patients were younger (61.0 vs. 63.8 years), had lower BMI (26.6 vs. 29.2 kg/m2), higher calculated MELD (9.9 vs. 7.8), and higher proportion of major liver resection (85.7% vs. 54.6%, all p < 0.01). Stenting was associated with increased bile leak (32.3% vs. 11.2%), sepsis (28.6% vs. 9.7%), and invasive intervention (36.0% vs. 13.3%, all p < 0.01). Stenting was also associated with increased product transfusion (46.6% vs. 24.7%), liver failure (23.6% vs. 8.9%), morbidity (55.9% vs. 26.8%), mortality (7.5% vs. 3.0%), readmission (21.7% vs. 13.8%), and reoperation (11.8 vs. 4.7%, all p < 0.01). Adjusting for age, gender, BMI, MELD, histology and major resection, stenting continued to independently contribute to bile leak (OR 4.39), sepsis (OR 2.99), invasive intervention (OR 3.42), liver failure (OR 2.57), transfusion (OR 2.03), morbidity (OR 2.98), and readmission (OR 1.92, all p < 0.01). Conclusion: Preoperative stenting is independently associated with increased bile leak, sepsis, invasive intervention, liver failure and readmission. These data suggest that avoidance of preoperative stenting, when feasible, may decrease short-term complications.

R1 resection in hilar cholangiocarcinoma might not translate to inferior patient survival; an intention to treat analysis

Background: Hilar cholangiocarcinoma (HC) represents an aggressive tumor embedded in an anatomically sensitive area. Surgeons must balance the goal of obtaining negative margins with the need to preserve critical vascular structures as well as enough proximal tissue to permit a feasible bilioenteric reconstruction. This study aims to revisit the importance of obtaining an R0 resection when excising HC in the era of modern adjuvant therapy. Methods: A retrospective review of a prospectively maintained database was employed to compile a list of patients with HC who were taken to the operating room with curative intent at our institution from 2008 to 2016. Those cases that resulted in resection were subjected to further analysis, with a focus on oncologic outcomes. Patients with both R0 and R1 margins underwent adjuvant chemoradiation. Results: 101 patients were included in the study. 71 resections were aborted after diagnostic laparoscopy and liver/portal ultrasonography, either because of peritoneal metastasis, or local disease extending beyond what was seen on preoperative imaging (Bismuth-Corlette T4/MSK T3). 30 patients underwent resection. Details of their cases and outcomes are included in Fig. 1. There were no cases of R2 resection. 2 year overall and progression free survival were similar between R0 and R1 resection groups (p = 0.86). Nodal status, grade, and lymphovascular invasion were also similar between the two groups. Conclusion: As with the resection of any malignancy, principles of oncologic resection should be adhered to when resecting cholangiocarcinoma. Striving for microscopically negative margins is one of those principles; however, given the technical difficulty of obtaining a proximal margin, it should be considered that R1 resection does not preclude a comparable oncologic outcome, provided patients are treated with adjuvant chemoradiation.Table 1Demographics, perioperative data, and complication data for HC resectionCharacteristicQuantityDemographic and procedural data Patients taken to the OR with curative intent101 Procedures where resection was actually performed30Male, No. (%)21 (70%)Female, No. (%)9 (30%)Age in years, median (range)63.5 (39–79)Major hepatectomy performed, No. (%)25 (83.3%)Bile duct resection alone, No. (%)5 (16.7%)Oncologic details AJCC T stage No. (%)T12 (6.7%)T216(53.3%)T312 (40%) Histologic Grade, No. (%)Well differentiated (G1)4(13.3%)Well-moderately differentiated (G1-2)4 (13.3%)Moderately differentiated (G2)12 (40%)Moderate-poorly differentiated (G2-3)7 (23%)Poorly differentiated (G3)3 (10%) Tumor size in mm, median (range)29 (8–70) R0 resection17 (57.7%) R1 resection13 (43.3%) Cases with lymphovascular invasion, No. (%)7 (23.3%) Cases with positive lymph nodes, No. (%)9 (30%) Cases with perineural invasion, No. (%)25 (83%)Outcomes data 30 day mortality, No. (%)2 (6.7%) 90 day mortality, No. (%)3 (10%) Median follow up, months30.5 2 year overall survival (%)90% 2 year progression free survival (%)63.3%2 year PFS with R0 resection64.7%2 year PFS with R1 resection62.0% Time to recurrence in months, median (range)21.3 (3.8–52.1)Abbreviations: HC, hilar Cholangiocarcinoma: AJCC, American Joint Committee on Cancer; PFS, progression free survival Open table in a new tab Abbreviations: HC, hilar Cholangiocarcinoma: AJCC, American Joint Committee on Cancer; PFS, progression free survival

Chemoradiotherapy for positive hepatic margin on cholangiocarcinoma

Background: Positive hepatic margin in resected cholangiocarcinoma influence the stump recurrence. However, impact of chemoradiotherapy (CRT) for positive hepatic margin on survival and recurrence was not fully evaluated. Methods: Two hundred ninety-five patients with cholangiocarcinoma who underwent surgical resection between 2002 and 2013 were included in this retrospective study. Clinical effect of chemoradiotherapy for positive hepatic margin on survival and recurrence and prognostic factors of cholangiocarcinoma were evaluated. Results: Hepatic margin was negative (hm−) in 257 and positive (hm+) in 38. Of 38 patients with positive hepatic margin, 20 patients received postoperative chemoradiotherapy and 18 did not. Hepatic stump recurrence was occurred in 13 patients. The incidence was significantly higher in patients with positive hepatic margins (16%) than those with negative hepatic margins (3%) (p = 0.003). Among patients with positive hepatic margins, the incidence was almost identical between patients with and without chemoradiotherapy; 17% (3/18) in hm+/CRT− and 15% (3/20) in hm+/CRT+ patients (p = 0.616). Median survival time was 48 months in hm−, 38 months in hm+/CRT−, 50 months in hm+/CRT+ patients, respectively. The differences were not significant between each group. Multivariate analysis revealed that presence of lymph node metastasis, histologic grade of G2/G3, and combined portal vein resection as the significant prognostic factors. However, performance of postoperative adjuvant chemoradiotherapy did not contribute the prolongation of survival. Conclusion: Chemoradiotherapy for positive hepatic ductal margin was not effective in survival and stump recurrence.

Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p<0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p=0.03) and overall survival [OS] (p=0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p=0.17; OS p=0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p=0.04) and OS (HR 2.09; p=0.02). Nuclear HuR expression did not affect the survival of enrolled patients. High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

Vascular resection and reconstruction for hilar cholangiocarcinoma

Completed surgical resection is the only treatment to patients with resectable hilar cholangiocarcinoma (HCCA). R0 resection is considered as a positive factor in long-term survive of patients. However, achieving negative surgical margins often ends in failure as the bile duct bifurcation is very close to the vascular inflow to the liver. Combined resection and reconstruction (CRR) of the portal vein (PV) and/or hepatic artery (HA), is introduced and has been performed widely. This paper focuses on this operation. Key words: Hilar cholangiocarcinoma; Combined resection and reconstruction; Portal vein; Hepatic artery

Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment

Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7–9.3) and high (HR 12.1, 95% CI 8.1–16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03–3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44–1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.

Retrospective study of postoperative chemoradiation of cholangiocarcinoma in South Korea: Efficacy, side effect, and prognostic factors.

486 Background: There is no estabilished consensus about chemoradiation therapy for resected cholangiocarcinoma, and many studies are ongoing. We tried to cofirm the effectiveness and side effects of chemoradiation after operation of cholangiocarcinoma and find the prognostic factors. Methods: We found the patients with cholangiocarcinoma who receieved chemoradiation after surgery between 2002 and 2015 from two hospitals in South Korea. We checked the baseline chareacteristics, efficacy and toxicities. And we tried to identify the prognostic factors for recurrence by statistical anaylsis. Results: We retrospectivally studied 51 cholangiocarcinoma patients. Median age was 64 (range 48-83), and Men was 30 patients (58.8%) of them. By location, there were 10 (19,6%) intrahepatic cholangiocarcinomas, 13 (25.5%) hilar cholangiocarcinoma, and 28 (54.9%) extrahepatic cholangiocarcinomas. All patient received 5-FU chemoradiation after surgery. R0 resections were 31 (60.8%), R1 resections were 20 (39.2%) There was recurrence with 35 (68.6%) patients. Median relapse free survival was 292 (range 86-1769) days. Locoregional recurrence were 16 (31.4%), and distant recurrences were 26 (51.0%). For hematological toxicity, the patients showed grade 3 toxicities, as leukopenia 5 (9.8%), anemia 1 (2.0%) , thrombocytopenia 1 (2.0%). For non-hematological toxicities, there were G3 toxicities as Infection 2 (4.0%), nausea/vomiting 1 (2.0%), Adhesive ileus 1 (2.0%), bleeding 1 (2.0%). For multivariate analysis, Tumor site (HR 1.88 (95% CI 1.09-3.23). P = 0.022) and modality of radiation therapy (HR 13.27 (95% CI, 3.56-49.50)), P &lt; 0.001) were statistically meaningful factors. Conclusions: Although this is a retrospective study, we found that the result of chemoradiation therapy for some patients showed good efficacy and tolerable toxicity. We could consider chemoradiation for adjuvant therapy in cholangiocarcinoma, especially for extrahepatic cholangiocarcinoma. And intensity-modulated radiation therapy should be performed than three-dimensional radiation therapy in cholangiocarcinoma.

Extended left hepatectomy for intrahepatic cholangiocarcinoma: hepatic vein reconstruction with in-situ hypothermic perfusion and extracorporeal membrane oxygenation

BackgroundLiver resection for intrahepatic cholangiocarcinoma (ICC) with invasion of the inferior vena cava (IVC) and hepatic veins (HV) is a challenging procedure.Case presentationWe report a case of a 63-year-old woman with a 6-cm, centrally located liver mass. Her biochemistry results were normal except for a Ca19–9 level of 1199 U/ml. The liver biopsy was consistent with ICC and 60% macrosteatosis. Abdominal CT scans revealed a large central mass invading the left HV, middle HV and right HV, infringing on their junction with the vena cava. An operation was planned using a 3-dimensional (3D) computer simulation model using dedicated software. We also describe a novel veno-portal-venous extracorporeal membrane oxygenation (VPV-ECMO) support with in-situ hypothermic perfusion (IHP) during this procedure. We aimed to perform an extended left hepatectomy and reconstruct 3 right HV orifices with an interposition jump graft to the IVC with total vascular exclusion (TVE) and IHP A supplemental video describing the preoperative planning, the operative procedure with the postoperative follow-up in detail is presented. After the patient was discharged, she developed a hepatic venous outflow obstruction 3 months postoperatively, which was effectively managed with hepatic venous stenting by interventional radiology. She is currently symptom free and without tumour recurrence at the 1-year follow-up.ConclusionsThis report demonstrates that extended left hepatectomy for IHC with IHP and VPV-ECMO is safe and feasible under the supervision of a highly experienced team.

The Limitations of Standard Clinicopathologic Features to Accurately Risk-Stratify Prognosis after Resection of Intrahepatic Cholangiocarcinoma

BackgroundThe 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. MethodsPatients 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. ResultsEight 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 < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09–1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell’s c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS − Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered “favorable.” ConclusionA 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.

Benefits of Laparoscopic Approach for Resection of Liver Tumors in Cirrhotic Patients

Liver resection in cirrhotic patients is associated with increased morbidity and mortality. The objective of this study was to compare short-term results of laparoscopic resection (LR) and open surgery (OS) for minor liver resection in patients with hepatocellular carcinoma (HCC) hepatocellularcarcinoma on nontumor cirrhotic liver (HCC/F4) and patients with colorectal cancer liver metastases (CRLMs) colorectal liver metastases on healthy liver (CRLM/F0). Between January 2005 and December 2014, all patients undergoing liver resection (n = 754) were included in this study. Liver resections for cholangiocarcinoma or benign tumor, major liver resection (≥3 segments), HCC on healthy liver, CRLM on cirrhotic liver, and liver resection with technically difficult accessibility (segments I, VII, and VIII) were excluded. The primary endpoint of the study was a validated composite endpoint (CEP), which included specific liver surgery complications (Clavien ≥III), allowing comparison of the postoperative course after LR versus OR for HCC/F4 patients and CRLM/F0 patients using propensity score (PS) analysis. Secondary endpoints were major postoperative morbidity according to the Clavien-Dindo classification (≥III) and intensive care unit (ICU) length of hospital stay (LOS) and overall LOS. The test group was defined as HCC/F4 patients operated by LR, and the control group was defined as HCC/F4 patients and CRLM/F0 patients operated by OS and CRLM/F0 patient operated by LR. Sixty patients (38.7%) underwent LR and 95 patients (61.3%) underwent OS. Surgery was performed for CRLM in 93 patients (60%) and for HCC in 62 patients (40%). No difference was demonstrated between HCC/F4 patients and CRLM/F0 patients in the LR group in terms of the CEP (7% versus 18.1%; P = .23), while a significant difference for the CEP was observed between HCC/F4 patients and CRLM/F0 patients after OS (50% versus 21%; P = .021). A higher rate of CEP was observed for HCC/F4 patients operated by OS compared to HCC/F4 patients operated by LR (50% versus 7.8%; P = .009). No significant difference in Clavien-Dindo score ≥III was observed between HCC/F4 patients and CRLM/F0 patients operated by LR (10% versus 4.5%; P = .98). A higher postoperative ascites rate was observed for HCC/F4 patients operated by OS compared to CRLM/F0 patients operated by OS (25% versus 2.8%; P = .006). This difference was no longer observed when HCC/F4 patients were compared to CRLM/F0 operated by LR (7.8% versus 2.8%; P = .09). The postoperative mortality rate was 1.8% and was not correlated with nontumor liver or surgical approach. A shorter LOS was observed for HCC/F4 patients operated by LR compared to HCC/F4 patients operated by OS (7.53 versus 17.13; P = .011). The laparoscopic approach for malignant liver tumor is associated with a lower specific complication rate. LR for HCC/F4 could eliminate excess morbidity and decrease LOS in patients with cirrhotic liver.

Recurrence after curative-intent resection of perihilar cholangiocarcinoma: analysis of a large cohort with a close postoperative follow-up approach

BackgroundAlthough several studies have been conducted on the patterns of recurrence in resected perihilar cholangiocarcinoma, they have many limitations. The aim of this study was to investigate recurrence after resection and to evaluate prognostic factors on the time to recurrence and recurrence-free survival. MethodsConsecutive patients who underwent curative-intent resection of perihilar cholangiocarcinoma between 2001 and 2012 were reviewed retrospectively. The Cox proportional hazards model was used for multivariable analysis. ResultsIn the study period, 402 patients underwent resection of perihilar cholangiocarcinoma (R0, n = 340; R1, n = 62). Radial margin positivity (n = 43, 69%) was the most common reason for R1 resection. The median follow-up of survivors was 7.4 years. The cumulative recurrence probability was higher in R1 than in R0 resection (86% vs 57% at 5 years, P < .001). Seventeen R0 patients had a recurrence over 5 years after resection. There was no difference in median survival time after recurrence between R0 and R1 resection (10 vs 7 months). The proportion of isolated locoregional recurrence was higher in R1 than in R0 resection (37% vs 16%, P < .001), whereas the proportion of distant recurrence was similar. In R0 resection, the independent prognostic factors for time to recurrence and recurrence-free survival were microscopic venous invasion and lymph node metastasis. ConclusionMore than half of patients with perihilar cholangiocarcinoma experience recurrence after R0 resection. These recurrences occur frequently within 5 years but occasionally after 5 years, which emphasizes the need for close and long-term surveillance. Adjuvant strategies should be considered, especially for patients with nodal metastasis or venous invasion even after R0 resection.

A case of metachronous ampullary cancer treated by pancreatoduodenectomy two years after hepatic resection for perihilar cholangiocarcinoma

A case of metachronous ampullary cancer treated by pancreatoduodenectomy two years after hepatic resection for perihilar cholangiocarcinoma

CEA but not CA19 – 9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma

CEA but not CA19 – 9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma

Prediction of thromboembolic complications after liver resection for cholangiocarcinoma: is there a place for thromboelastometry?

: Postoperative venous thromboembolism has a poor prognosis in patients with cancer. We aimed to investigate the utility of thromboelastometry in detecting the risk of postoperative venous thromboembolism in patients with cholangiocarcinoma. We prospectively included patients submitted to liver resection for cholangiocarcinoma at our hospital between May 2011 and July 2014. Patients undergoing major hepatectomy for adult living donor transplantation in the same time period served as a control group. Thromboelastometry was performed before anesthesia. Postoperative venous thrombotic events were recorded in the 6 months after surgery. Twenty-seven patients with cholangiocarcinoma and 17 living-donor liver transplantation patients were included. Maximum clot firmness and its derivative parameter G, pointed to hypercoagulability in patients with cholangiocarcinoma, whereas all parameters were within normal ranges in controls. Six postoperative thrombotic events were recorded: four portal vein thrombosis and two deep venous thrombosis, all in patients with cholangiocarcinoma. Patients with cholangiocarcinoma who displayed thrombotic complications showed a nonsignificant trend to more pronounced hypercoagulability compared with those without. The results suggest that first, in patients with cholangiocarcinoma, despite standard thromboprophylaxis, thrombotic events remain a substantial problem, and, second, thromboelastometry may be useful in identifying patients with cholangiocarcinoma at risk of postoperative venous thromboembolism. Large prospective studies are warranted to confirm these results.

Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma.

We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0+S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1+CCRT group, n=19) or adjuvant radiation therapy (RT) alone (R1+RT group, n=13). During the median follow-up period of 26months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0+S group; 71.8, 57.8, and 57.9% for R1+CCRT group; and 16.8, 9.6, and 15.4% for R1+RT group, respectively. Multivariate analysis revealed that the R1+CCRT group did not show any significant difference in survival rates compared with the R0+S group. The R1+RT group had lower LRRFS [hazard ratio (HR) 3.008; p=0.044], DFS (HR 2.364; p=0.022), and OS (HR 2.417; p=0.011) when compared with the R0+S and R1+CCRT group. A lack of significant survival difference between R0+S group and R1+CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor.

CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma

Cholangiocarcinoma (CCA) represents a rare form of primary liver cancer with increasing incidence but dismal prognosis. Surgical treatment has remained the only potentially curative treatment option, but it remains unclear which patients benefit most from liver surgery, highlighting the need for new preoperative stratification strategies. In clinical routine, CA19-9 represents the most widely used tumor marker in CCA patients. However, data on the prognostic value of CA19-9 in CCA patients are limited and often inconclusive, mostly due to small cohort sizes. Here, we investigated the prognostic value of CA19-9 in comparison with other standard laboratory markers in a large cohort of CCA patients that underwent tumor resection. Of note, while CA19-9 and CEA were able to discriminate between CCA and healthy controls, CEA showed a higher accuracy for the differentiation between CCA and patients with primary sclerosing cholangitis (PSC) compared to CA19-9. Furthermore, patients with elevated levels of C-reactive protein (CRP), CA19-9 or CEA showed a significantly impaired survival in Kaplan-Meier curve analysis, but surprisingly, only CEA but not CA19-9 represented an independent predictor of survival in multivariate Cox-regression analysis. Our data suggest that CEA might help to identify CCA patients with an unfavourable prognosis after tumor resection.

Proximal Resection Margins: More Prognostic than Distal Resection Margins in Patients Undergoing Hilar Cholangiocarcinoma Resection.

PurposeEven though the therapeutic gold standard of hilar cholangiocarcinoma (HCCA) resection is cancer-free resection margin (RM), surgical treatment still remains challenging. This study evaluated the prognostic significance of RM status in resected HCCA patients and identified survival prognostic factors.Materials and MethodsWe reviewed records of 96 HCCA patients who underwent surgery from 2001 to 2012 and analyzed the RM status and prognostic factors that affecting survival.ResultsNegative RM (n=31, 33%) was significantly associated with better survival vs. positive RM (n=65, 67%) (mean survival time [MST], 33 months vs. 21 months; p=0.011). Margins with histological findings of non-dysplastic epithelium, low-grade dysplasia, and carcinoma in situ were not associated with survival differences (MST, 33 months vs. 33 months vs. 30 months; p=0.452), whereas positive margins were associated with poorer survival relative to carcinoma in situ (MST, 30 months vs. 21 months; p=0.050). Among patients with R0 resection, narrow (≤ 5 mm) and wide (> 5 mm) margins were not associated with survival differences (MST, 33 months vs. 30 months; p=0.234). Although positive proximal RM was associated with poorer survival compared to negative RM (MST, 19 vs. 33; p=0.002), no survival difference was observed between positive and negative distal RMs (MST, 30 vs. 33; p=0.628). Proximal RM positivity (hazard ratio [HR], 2.688; p=0.007) and nodal involvement (HR, 3.293; p < 0.001) were independent survival prognostic factors.ConclusionA clear RM, especially proximal RM status, was significant prognosticator, and proximal bile duct resection to the greatest technically feasible extent may be necessary, with careful consideration of the potential morbidity and oncologic outcomes after resection. However, an aggressive approach to obtain a negative distal RM might be controversial and should be considered carefully, depending on the patient's status.

Antiviral therapy improves survival in patients with HBV infection and intrahepatic cholangiocarcinoma undergoing liver resection

The impact of hepatitis B virus (HBV) infection on outcomes after resection of intrahepatic cholangiocarcinoma (ICC) has not been reported. The aim of this study was to examine the impact of antiviral therapy on survival outcomes after liver resection for patients with ICC and underlying HBV infection. Data on 928 patients with ICC and HBV infection who underwent liver resection at two medical centers between 2006 and 2011 were analyzed. Data on viral reactivation, tumor recurrence, cancer-specific survival (CSS) and overall survival (OS) were obtained. Survival rates were analyzed using the time-dependent Cox regression model adjusted for potential covariates. Postoperative viral reactivation occurred in 3.3%, 8.3% and 15.7% of patients who received preoperative antiviral therapy, who did not receive preoperative antiviral therapy with a low, or a high HBV-DNA level (< or ≥2,000 IU/ml), respectively (p <0.001). A high viral level and viral reactivation were independent risk factors of recurrence (hazard ratio [HR] 1.22 and 1.34), CSS (HR 1.36 and 1.46) and OS (HR1.23 and 1.36). Five-year recurrence, CSS and OS were better in patients who received antiviral therapy (70.5%, 46.9% and 43.0%) compared with patients who did not receive antiviral therapy and had a high viral level (86.5%, 20.9% and 20.5%, all p <0.001), respectively. The differences in recurrence, CSS and OS were minimal compared with no-antiviral therapy patients with a low viral level (71.7%, 35.5% and 33.5%, p = 0.057, 0.051 and 0.060, respectively). Compared to patients with a high viral level who received no antiviral therapy, patients who initiated antiviral therapy either before or after surgery had better long-term outcomes (HR 0.44 and 0.54 for recurrence; 0.38 and 0.57 for CSS; 0.46 and 0.54 for OS, respectively). Viral reactivation was associated with worse prognoses after liver resection for HBV-infected patients with ICC. Antiviral therapy decreased viral reactivation and prolonged long-term survival for patients with ICC and a high viral level. Postoperative hepatitis B virus reactivation was associated with an increased complication rate and a decreased survival rate after liver resection in patients with ICC and hepatitis B virus infection. Antiviral therapy before liver resection reduced the risk of postoperative viral reactivation. Both pre- and postoperative antiviral therapy was effective in prolonging patient survival.