Unresectable Extrahepatic Cholangiocarcinoma Research Articles

Photodynamic therapy combined with systemic chemotherapy for unresectable extrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

Extrahepatic cholangiocarcinoma (ECC) is a tumor with high invasiveness and poor outcome. The current treatments for unresected ECC are not ideal. Novel strategies are needed to improve the outcomes of patients with unresected ECC. Photodynamic therapy (PDT) plus chemotherapy is one of the promising interventions for ECC patients. We conducted this systematic review to determine the efficacy and safety of PDT plus chemotherapy in unresected ECC patients. Databases of PubMed, Cochrane Library, Embase, and Web of science were searched from inception to July 2022. Studies that compared PDT plus chemotherapy to PDT alone or chemotherapy alone in patients with unresected ECC were included. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled for overall survival (OS) and adverse events, respectively. Seven eligible studies were finally included. There are four studies on PDT plus chemotherapy vs. chemotherapy alone and three studies on PDT plus chemotherapy vs. PDT alone. The meta-analysis showed that PDT plus chemotherapy had a significantly better OS than chemotherapy or PDT alone (PDT+chemotherapy vs. chemotherapy alone, HR: 0.69, p=0.02; PDT+chemotherapy vs. PDT alone, HR:0.36, p<0.01). The occurrence of cholangitis, abscess, and photosensitivity reaction in PDT plus chemotherapy were comparable to either chemotherapy alone or PDT alone (p>0.05). The combination of PDT and chemotherapy can improve patient survival for unresected ECC without increased adverse events. It may be a potential standard therapy in the future management of ECC.

Myocarditis and myositis/myasthenia gravis overlap syndrome induced by immune checkpoint inhibitor followed by esophageal hiatal hernia: A case report and review of the literature

Immunotherapy with programmed death 1 (PD-1) inhibitor has shown activity as first- or second-line treatment for various metastatic human malignancies. Immune-related adverse events (irAEs) are now well-described, and most organ sites are potentially influenced, but the prevalence of myocarditis and myositis/myasthenia gravis (MG) overlap syndrome following esophageal hiatal hernia induced by immunotherapy is rarely reported. Here, we describe a 71-year-old woman with a progressed unresectable extrahepatic cholangiocarcinoma and biliary obstruction. She had no prior history of muscle weakness and neuromuscular disease with a normal body mass index. She was treated with sintilimab as a rescue regimen of immunotherapy. After the first cycle of treatment, she experienced a grade 4 myopathy including simultaneous myositis, myalgia, and myocarditis due to multiple injuries in her cardiac, skeletal, and ocular muscles. She had elevated levels of creatine kinase (CK), cardiac troponin I, and myoglobin (MYO), but MG and myositis-specific and myositis-related antibodies were negative. Immunotherapy was discontinued and pulse high-dose methylprednisolone with a slow tapering and intravenous immunoglobulin (IVIG) was initiated. Two weeks later, the patient's clinical presentation improved significantly. A subsequent cardiac magnetic resonance (MR) examination revealed an old myocardial injury that may be a result of immune-related cardiac toxicity. In the third month following the PD-1 inhibitor therapy, she restarted systemic chemotherapy in combination with an anti-angiogenic agent but without immunotherapy. Half a year later, she complained of repeated abdominal distension and radiographic examinations and endoscopy showed a clinically confirmed diagnosis of sliding hiatal hernia of the esophagus and gastroesophageal reflux disease. Due to mild symptoms associated with gastroesophageal reflux, she was suggested close monitoring with acid secretion blockade rather than immediate surgical intervention. The severity for patients with myositis and myocarditis accompanied without MG is similar to those with MG. Considering the use of PD-1 inhibitors is increasing in cancer patients, physicians should therefore pay more attention to immunotherapy-induced myocarditis with myositis/MG overlap syndrome. Since we hypothesize diaphragmatic hiatal hernia as a potential consequence of immunotherapy-induced myositis, reports on hiatal hernias subsequent to immunotherapy-induced myositis are needed.

Endobiliary Radiofrequency Ablation Combined with Gemcitabine and Cisplatin in Patients with Unresectable Extrahepatic Cholangiocarcinoma.

Background: Endobiliary radiofrequency ablation (RFA) is a promising treatment modality for patients with extrahepatic cholangiocarcinoma (eCCA). However, no study has investigated the combined use of endobiliary RFA and gemcitabine plus cisplatin (GC) chemotherapy. This study aimed to examine the feasibility and efficacy of endobiliary RFA with GC therapy for patients with unresectable eCCA. Methods: The study outcomes included overall survival (OS), progression-free survival (PFS), time to recurrent biliary obstruction (RBO), and adverse events associated with the treatment. These parameters were retrospectively compared between 25 patients who underwent RFA with self-expandable metal stent (SEMS) placement followed by GC therapy (with-RFA group) and a control cohort of 25 patients who underwent SEMS placement alone and GC therapy (without-RFA group). Results: The median time to RBO was significantly longer in the with-RFA group (10.7 versus 5.2 months, p = 0.048). The median OS was significantly higher in patients with locally advanced tumors in the with-RFA group (23.1 versus 16.6 months, p = 0.032), but did not differ significantly in patients with metastasis (11.4 versus 8.5 months, p = 0.180). Similarly, the median PFS was significantly higher in the with-RFA group in patients with locally advanced disease (10.1 versus 7.3 months, p = 0.015), while there was no significant difference in patients with metastasis (5.4 versus 4.4 months, p = 0.529). The rates of various toxicities did not differ significantly between the groups. Conclusions: Endobiliary RFA prolonged the patency period of uncovered SEMS combined with GC therapy in patients with eCCA. Although RFA also yielded survival benefits, its effect was restricted to locally advanced tumors.

Advances in Application of PDT Combined with Multiple Therapies on Unresectable Extrahepatic Cholangiocarcinoma

Advances in Application of PDT Combined with Multiple Therapies on Unresectable Extrahepatic Cholangiocarcinoma

Photodynamic Therapy (PDT), Radiofrequency Ablation (RFA) With Biliary Stents in Palliative Treatment of Unresectable Extrahepatic Cholangiocarcinoma: A Systematic Review and Meta-analysis.

Extrahepatic unresectable cholangiocarcinoma carries a dismal prognosis. In addition to biliary drainage by stent placement; photodynamic therapy (PDT) and radiofrequency ablation (RFA) have been tried to prolong survival. In this meta-analysis, we appraise the current known data on the use of PDT, RFA in the palliative treatment of extrahepatic unresectable cholangiocarcinoma. We searched multiple databases from inception through July 2020 to identify studies that reported on PDT and RFA. Pooled rates of survival, stent patency, 30-, 90-day mortality, and adverse events were calculated. Study heterogeneity was assessed using I2% and 95% prediction interval. A total of 55 studies (2146 patients) were included. A total of 1149 patients underwent treatment with PDT (33 studies), 545 with RFA (22 studies), and 452 patients with stent-only strategy. The pooled survival rate with PDT, RFA, and stent-only groups was 11.9 [95% confidence interval (CI): 10.7-13.1] months, 8.1 (95% CI: 6.4-9.9) months, and 6.7 (95% CI: 4.9-8.4) months, respectively. The pooled time of stent patency with PDT, RFA, and stent-only groups was 6.1 (95% CI: 4.2-8) months, 5.5 (95% CI: 4.2-6.7) months, and 4.7 (95% CI: 2.6-6.7) months, respectively. The pooled rate of 30-day mortality with PDT was 3.3% (95% CI: 1.6%-6.7%), with RFA was 7% (95% CI: 4.1%-11.7%) and with stent-only was 4.9% (95% CI: 1.7%-13.1%). The pooled rate of 90-day mortality with PDT was 10.4% (95% CI: 5.4%-19.2%) and with RFA was 16.3% (95% CI: 8.7%-28.6%). PDT seemed to demonstrate better overall survival and 30-day mortality rates than RFA and/or stent-only palliation.

Extrahepatic cholangiocarcinoma: Current status of endoscopic approach and additional therapies.

The prognosis of patients with advanced or unresectable extrahepatic cholangiocarcinoma is poor. More than 50% of patients with jaundice are inoperable at the time of first diagnosis. Endoscopic treatment in patients with obstructive jaundice ensures bile duct drainage in preoperative or palliative settings. Relief of symptoms (pain, pruritus, jaundice) and improvement in quality of life are the aims of palliative therapy. Stent implantation by endoscopic retrograde cholangiopancreatography is generally preferred for long-term palliation. There is a vast variety of plastic and metal stents, covered or uncovered. The stent choice depends on the expected length of survival, quality of life, costs and physician expertise. This review will provide the framework for the endoscopic minimally invasive therapy in extrahepatic cholangiocarcinoma. Moreover, additional therapies, such as brachytherapy, photodynamic therapy, radiofrequency ablation, chemotherapy, molecular-targeted therapy and/or immunotherapy by the endoscopic approach, are the nonsurgical methods associated with survival improvement rate and/or local symptom palliation.

Intraluminal Brachytherapy in Unresectable Extrahepatic Biliary Duct Cancer: An Italian Pooled Analysis.

To evaluate the outcome of patients with unresectable extrahepatic cholangiocarcinoma (CC) treated with external-beam radiotherapy (EBRT) and concurrent chemotherapy (CT) with or without intraluminal brachytherapy (ILBT) boost or with definitive ILBT. A pooled analysis of patients with non-metastatic unresectable CC was performed. They were treated in three different institution with EBRT plus CT with or without an ILBT boost. Some patients received only ILBT with curative dose. Seventy-three patients were included in the analysis. Thirty-nine patients (53%) received EBRT treatment with ILBT boost (18 patients with CT during EBRT), while 28 patients (38%) were treated with EBRT (CT in 26 patients) and 6 patients (8.2%) with definitive ILBT (2 patients with CT). CT was administered including either the use of gemcitabine or 5-fluorouracil. With a median follow-up of 16 month (range=1-94 months), median overall survival (OS) was 16 months. Overall median LC was 16 months and patients who underwent ILBT had a better local control (LC) (p=0.018). The role of ILBT in unresectable CC is not yet supported by robust evidence in the literature. However, within this limit, preliminary results seem to suggest an improved local control in patients treated with ILBT, almost comparable to the ones of standard chemo-radiotherapy (CRT).

Endoscopic radiofrequency ablation plus a novel oral 5-fluorouracil compound versus radiofrequency ablation alone for unresectable extrahepatic cholangiocarcinoma

Endoscopic radiofrequency ablation (RFA) is a new ablative treatment for unresectable extrahepatic cholangiocarcinoma (EHCC). A novel 5-fluorouracil compound, S-1 (Taiho Pharmaceutical Co, Ltd, Tokushima Plant. Japan), has been widely used as a key drug with first-line or second-line chemotherapy for the treatment of advanced cholangiocarcinoma. The aim of this study was to evaluate the clinical efficacy and safety of endoscopic RFA combined with S-1 for the treatment of unresectable locally advanced EHCC. Patients with unresectable EHCC were prospectively randomized to 1 of 2 groups: the RFA+ S-1 group and the RFA group. Median overall survival (OS), stent patency time, Karnofsky performance status (KPS) score, and adverse events rate were analyzed. The median OS was longer in the RFA+ S-1 group (n= 37) than that in the RFA group (n= 38) (16.0 months [95% confidence interval, 13.1-19.0] vs 11.0 months [95% confidence interval, 9.7-12.3]; P< .001). Stent patency time was significantly longer in the RFA+ S-1 group than that in the RFA group (6.6 ± 1.5 vs 5.6 ± .1 months, P= .014). KPS scores at postoperative month 9 (51.6 ± 17.0 vs 40.4 ± 16.4, P= .012) and month 12 (35.2 ± 18.3 vs 23.9 ± 11.4, P= .014) were all higher in the RFA+ S-1 group than those in the RFA group (P< .05). The incidence of ERCP-related adverse events was not significantly different between RFA+S-1 and RFA groups (8.1% vs 10.5%, P > .05). For the treatment of locally advanced EHCC, endoscopic RFA combined with S-1 is associated with longer survival and stent patency and improved functional status than RFA alone. (Clinical trial registration number: NCT02592538.).

Photodynamic therapy may provide a benefit over systemic chemotherapy among non-surgically managed patients with extrahepatic cholangiocarcinoma.

Systemic chemotherapy is the standard treatment for patients with unresectable extrahepatic cholangiocarcinoma (ECC), however, the survival benefit of chemotherapy is limited. Photodynamic therapy (PDT) has been associated with improved survival among patients with advanced ECC, yet utilization of PDT remains low. We sought to compare the outcomes of patients with unresectable ECC following treatment with PDT versus chemotherapy. A review of the National Cancer Database was conducted to identify patients with ECC who were nonsurgically managed between 2004 and 2013. Overall survival (OS) of patients receiving PDT vs systemic chemotherapy was compared using propensity score matching. After propensity matching (PDT, n = 59; chemotherapy, n = 177), 5-year OS was 17.6% (95% confidence interval [CI], 9.0%-28.6%) among patients who underwent PDT vs 3.8% (95%CI, 0.4%-14.0%) among patients receiving chemotherapy (P < .001). On multivariable analysis PDT was associated with an OS benefit (hazard ratio, 0.72; 95%CI, 0.52-0.998; P = .048). Subset analysis of patients receiving PDT only (n = 45) and patients receiving chemotherapy demonstrated similar results. In subset analysis of patients undergoing PDT-only vs PDT-chemotherapy, OS was comparable. PDT was associated with a survival benefit compared with chemotherapy alone among patients with unresectable ECC.

Combined photodynamic therapy with systemic chemotherapy for unresectable cholangiocarcinoma.

Chemotherapy with gemcitabine and cisplatin is the current standard for patients with unresectable cholangiocarcinoma. Local photodynamic therapy has also demonstrated benefit in patients with extrahepatic cholangiocarcinoma. To evaluate the benefit of photodynamic therapy in combination with systemic chemotherapy in advanced extrahepatic cholangiocarcinoma. Three hundred and fifty-three patients diagnosed with cholangiocarcinoma between 2004 and 2016 were treated at the University Hospital of Bonn, Germany. Of these, 96 suffering from unresectable extrahepatic cholangiocarcinoma were included. Patients were stratified according to treatment: combination photodynamic therapy and chemotherapy (36 patients), photodynamic therapy alone (34 patients), and chemotherapy alone (26 patients). Combined photodynamic therapy with chemotherapy resulted in significantly longer overall survival than chemotherapy alone (P=0.022). Median survival was 20months in the combination group (95% CI: 16.38-23.62), 15months in the photodynamic alone group (95% CI: 10.02-19.98) and 10months in the chemotherapy alone group (95% CI: 8.45-11.55). In multivariate analysis, combination therapy and photodynamic therapy alone (HR: 0.41, 95% CI: 0.22-0.77, P=0.006), metal stenting, and radiofrequency ablation were independent predictors of longer survival. Combination photodynamic therapy and chemotherapy was well tolerated and resulted in significantly longer survival than chemotherapy alone. Application of photodynamic therapy significantly correlated with longer survival, demonstrating benefit in advanced cholangiocarcinoma. Thus, photodynamic therapy should be considered during therapeutic decision making in advanced cholangiocarcinoma.

Complete Response to Chemotherapy in A Patient with Unresectable Extrahepatic Cholangiocarcinoma

Introduction: Biliary tract cancer (BTC) is an uncommon tumor with bad prognosis. There is no curative treatment for patients with unresectable disease at diagnosis. There is a limited experience with second-line chemotherapy in advanced BTC since clinical trials are difficult to perform due to the rarity and heterogeneity of these tumors. Recent molecular studies have increased our understanding of the pathogenetic mechanism that underly the development of cholangiocarcinoma. These will help us to determine the significance of molecular alterations that occur in this disease and will direct the development of targeted therapy. Case Report: This case report describes a radiological complete response after three cycles of second-line chemotherapy with the combination of capecitabine and oxaliplatin in a patient with unresectable extrahepatic cholangiocarcinoma, after treatment with the combination of gemcitabine and cisplatin as first-line chemotherapy. Conclusion: Our case suggests that selected patients may demonstrate very good responses to chemotherapy. There is an urgent need to identify different molecular subtypes that could direct management of these patients.

Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma.

PurposeTo evaluate the effect of escalated dose radiation therapy (EDR, defined as doses >50.4 Gy in 28 fractions [59.5 Gy BED]) on overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) of patients with unresectable extrahepatic cholangiocarcinoma (EHCC).MethodsA consecutive cohort of 80 patients who underwent radiotherapy for unresectable EHCC from 2001 to 2015 was identified. Demographic, tumor, treatment, toxicity, and laboratory variables were collected. The maximal RT doses ranged from 30 to 75 Gy (median 50.4 Gy, at 1.8‐4.5 Gy/fraction). Gross tumor volume (GTV) coverage by maximal dose in EDR group ranged from 38% to 100%. Kaplan–Meier method was used to estimate OS, FFLP, and FFDP. Univariate and multivariate Cox regression models were analyzed.ResultsAfter radiotherapy, median OS, FFLP, and FFDP were 18.7, 22.6, and 24.3 months, respectively. There was no significant difference in OS or FFLP between patients who received EDR to portions of the GTV and patients who did not. On multivariate analysis, bigger GTV, age, and ECOG performance status were independently associated with shorter OS. Local progression on chemotherapy prior to RT was independently associated with shorter FFLP. High baseline neutrophil/lymphocyte ratio (>5.3) was independently associated with shorter FFDP. Toxicity grades were similar in EDR and lower doses except lymphopenia which was higher in EDR (P = 0.053).Conclusions EDR to selective portions of the GTV may not benefit patients with unresectable EHCC despite having acceptable toxicity. New methods to improve local control and survival for unresectable EHCC are needed.

Efficacy and safety of endoscopic radiofrequency ablation for unresectable extrahepatic cholangiocarcinoma: a randomized trial

Endoscopic placement of biliary stents to relieve jaundice is the main palliative treatment for unresectable extrahepatic cholangiocarcinoma. Endoscopic biliary radiofrequency ablation (RFA) has been reported to prolong stent patency, which may be beneficial in improving patient survival. However, available evidence is still insufficient, as most reported studies are retrospective case series. The aim of this study was to explore the clinical effect and safety of RFA in patients with unresectable extrahepatic cholangiocarcinoma. 65 patients with unresectable extrahepatic cholangiocarcinoma, except Bismuth type III and IV hilar cholangiocarcinoma, were enrolled and randomly underwent either RFA combined with biliary stenting (RFA + stent group; n = 32) or biliary stent only (stent-only group; n = 33). Overall survival time, stent patency period, and postoperative adverse events were recorded. In the 21-month follow-up period, the overall mean survival time was significantly longer in the RFA + stent group than in the stent-only group (13.2 ± 0.6 vs. 8.3 ± 0.5months; P < 0.001). The mean stent patency period of the RFA + stent group was also significantly longer than that of the stent-only group (6.8 vs. 3.4months; P = 0.02). There was no significant difference in the incidence of postoperative adverse events between the two groups (6.3 % [2/32] vs. 9.1 % [3/33]; P = 0.67). Endoscopic RFA combined with stenting can significantly prolong survival and the stent patency period without increasing the incidence of adverse events in patients with extrahepatic cholangiocarcinoma patient, except Bismuth type III and IV hilar cholangiocarcinoma. This approach can be considered as a safe and effective palliative treatment for these patients.

Tu1404 Endoscopic Biliary Radiofrequency Ablation Prolong the Survival of Patients With Unrespectable Extrahepatic Cholangiocarcinoma

To explore the effect of radiofrequency ablation (RFA) on survival time and stent patency period in patients with unresectable extrahepatic cholangiocarcinoma (EHCC).

Treatment of unresectable extrahepatic cholangiocarcinoma using hematoporphyrin photodynamic therapy: A prospective study

BackgroundThe available evidence of Photodynamic therapy (PDT) combined with stent placement treatment for unresectable extrahepatic cholangiocarcinoma (EHCC) is still insufficient. It also remains unclear whether PDT influences systemic inflammatory response. AimTo explore the clinical efficacy and safety of the combination treatment and the systemic inflammatory response in patients with EHCC. MethodsPatients with unresectable EHCC underwent either the combined treatment using Hematoporphyrin PDT and stent placement (PDT+stent group, n=12) or stent-only (stent group, n=27). The primary end-point was overall survival. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. Quality of life was assessed using the Karnofsky performance scale (KPS) every 3 months. ResultsAverage survival time (13.8 vs. 9.6 months), and 6-month (91.7% vs. 74.1%), and 1-year (58.3% vs. 3.7%) survival rates of PDT+stent group were significantly increased compared with the stent group. KPS scores in the PDT+stent group were significantly improved. TNF-α and IL-6 levels were significantly increased in the PDT+stent group. ConclusionHematoporphyrin-PDT combined with stent placement is an effective and safe treatment for EHCC. The treatment might promote systemic inflammatory response.

Stereotactic body radiotherapy (SBRT) for locally advanced extrahepatic and intrahepatic cholangiocarcinoma

ObjectivesWe report single-institution clinical efficacy and safety outcomes for patients with unresectable locally advanced cholangiocarcinoma who were treated with stereotactic body radiation therapy (SBRT) and a subset of patients who received neoadjuvant SBRT and chemotherapy as part of an orthotopic liver transplantation (OLT) protocol. Methods and materialsFrom October 2008 to June 2015, 31 consecutive patients with unresectable extrahepatic (n = 25) or intrahepatic (n = 6) cholangiocarcinoma were treated with SBRT and retrospectively analyzed. Four patients underwent liver transplantation, and 1 underwent resection. SBRT was delivered in 5 fractions with a median dose of 40 Gy. Toxicity was scored using the Common Terminology Criteria for Adverse Events Version 4.0. Overall survival (OS), time to progression, and local control were estimated using the Kaplan-Meier method. ResultsThe median follow-up time was 11.5 months. The 1- and 2-year OS rates were 59% and 33%, respectively, with a median survival of 15.7 months. The 1- and 2-year freedom from progression was 67% and 34%, respectively. Median time to progression was 16.8 months. Nine patients had local failure. The actuarial 1- and 2-year local control rates were 78% and 47%, respectively. Among patients who also had OLT, the median OS was 31.3 months. Twenty-four patients (77%) experienced some form of acute grade 1-2 toxicity, most commonly fatigue or pain. Five patients (16%) experienced grade ≥3 toxicity. ConclusionsSBRT is a promising option for patients with unresectable or recurrent cholangiocarcinoma either as a component of neoadjuvant therapy prior to OLT or as part of definitive therapy for patients who are unresectable and not eligible for transplantation.

Comparison of external beam radiation and brachytherapy to external beam radiation alone for unresectable extrahepatic cholangiocarcinoma.

Extrahepatic cholangiocarcinoma (EHC) is a rare malignancy with a relatively poor prognosis. There are no randomized, prospective data to help define the optimal method of radiation delivery for unresectable EHC. The purpose of this study was to evaluate the benefit of adding brachytherapy to external beam radiation therapy (EBRT) for unresectable EHC. A retrospective review of 1,326 patients with unresectable EHC using the Surveillance, Epidemiology, and End Results (SEER) database was completed. Kaplan-Meier methods were used to analyze the primary endpoint, overall survival. Univariate and multivariate analysis was performed to identify and control for potential confounding variables, including age at diagnosis, sex, stage, grade, histology, race, year of diagnosis, and reason for no surgery. Of the 1,326 patients with unresectable EHC, 1,188 (92.9%) received EBRT only, while 91 (7.1%) received both EBRT and brachytherapy. Patients receiving combined modality radiation therapy were more likely to be treated prior to the year 2000. Median overall survival for patients receiving EBRT and EBRT plus brachytherapy was 9 and 11 months, respectively (P=0.04). Cause specific survival was 12 months for those receiving EBRT only, and 15 months for those who received EBRT + brachytherapy (P=0.10). Survival analysis performed on patients with locoregional disease only revealed a trend towards prolonged overall survival with those receiving EBRT + brachytherapy (P=0.08). Multivariate analysis revealed grade and stage of disease were correlated with both overall survival and cause specific survival (P≤0.05). Among patients with unresectable EHC, the addition of brachytherapy to EBRT is associated with a prolonged median overall survival. However, the use of brachytherapy boost decreased in the last decade of the study.

Metal Stenting with or without Endobiliary Radiofrequency Ablation for Unresectable Extrahepatic Cholangiocarcinoma

Background: Retrospective comparison of stent patency and survival of patients with unresectable extrahepatic cholangiocarcinoma (CCA) treated by placement of self-expanding metal stents (SEMS) with or without endobiliary radiofrequency ablation (ERFA). Methods: Between January 2010 and September 2014, 76 patients with biliary obstruction caused by unresectable extrahepatic CCA (27 patients with Bismuth type I hilar CCA and 49 patients with distal CCA) were recruited into this study. Patients either received ERFA with SEMS (n = 34) or SEMS only (n = 42). Stent patency and survival of both groups were compared and predictors for overall survival were analyzed. Results: Demographic data were not different between the two groups. Complication rates of both groups were similar. Thirty-day stent patency was obtained in all patients and the median stent patency in the ERFA + SEMS group (9.5 months, 4.5 - 14.0 months) was significantly longer than that in the SEMS group (8.4 months, 4.9 - 11 months) (P = 0.024). The overall survival curve in the ERFA + SEMS group was significantly better than that of the SEMS group (P = 0.036). Multivariate Cox proportional hazards regression analyses showed that ERFA, tumor AJCC stage, extrahepatic CCA type, serum albumin and adjuvant chemotherapy were significant prognostic factors for overall patient survival. Conclusions: ERFA is effective for unresectable extrahepatic CCA and may improve metal stent patency and patient survival for unresectable extrahepatic CCA with biliary obstruction. Prospective randomized trials will be needed to confirm these findings.

[Concurrent chemoradiotherapy for locally advanced unresectable extrahepatic cholangiocarcinoma: a report of 19 cases].

To evaluate the efficacy and toxicity of concurrent chemoradiotherapy for patients with locally advanced unresectable extrahepatic cholangiocarcinoma. Thirty-eight patients with locally advanced unresectable extrahepatic cholangiocarcinoma admitted in Shaoxing People's Hospital from February 2007 to February 2012 were enrolled in the study. They were randomized into sequential chemoradiotherapy (n=19) or concurrent chemoradiotherapy group (n=19). All patients were treated with intensity modulated radiation therapy (IMRT). Patients in concurrent chemoradiotherapy group received the regimen of gemcitabine plus oxaliplatin. Tumor response and adverse effects were observed periodically. The primary end points were disease progression-free survival (PFS) and overall survival (OS). The response rates of sequential chemoradiotherapy and concurrent chemoradiotherapy groups were 42.1% (8/19) and 63.2% (12/19). The disease control rates of them were 78.9% (15/19) and 84.2% (16/19))， respectively. The median PFS of sequential chemoradiotherapy group and concurrent chemoradiotherapy group was 8.3 (95%CI: 7.6-9.0) and 10.4 months (95%CI: 9.4-11.4, P=0.037), and the median OS in two groups were 14.2 (95%CI: 12.6-15.8) and 15.6 months (95%CI: 14.2-17.0, P=0.095), respectively. The major adverse reactions were controllable hematology toxicity and gastrointestinal reaction. There was no significant difference in incidence of adverse reactions between two groups (P>0.05). Sequential chemoradiotherapy and concurrent chemoradiotherapy may improve PFS and OS in patients with locally advanced unresectable extrahepatic cholangiocarcinoma, and both are well-tolerated. In addition, concurrent chemoradiotherapy might provide additional PFS benefit and would be preferable.

Clinical features and survival outcome of locally advanced extrahepatic cholangiocarcinoma.

Backgrounds/AimsLittle is known about clinical features and survival outcome in locally advanced unresectable extrahepatic cholangiocarcinoma (EHC). The aim was to investigate the clinical features and the survival outcome in these patients, and to evaluate the role of palliative resections in locally advanced unresectable EHC.MethodsBetween 1995 and 2007, 280 patients with locally advanced unresectable EHC were identified. Clinical, pathologic, and survival data were investigated. A comparative analysis was done between those who received palliative resection (PR) and those who were not operated on (NR).ResultsThe overall median survival of the study population was 10±1 months, and the 3- and 5-year survival rates (YSR) were 8.5% and 2.5%, respectively. The median survival, 3- and 5-YSR of PR were 23 months, 32.1% and 13.1%, respectively. For NR, they were 9 months, 3.9% and 0%, which were significantly worse than PR (p<0.001). In univariate analysis, T classification, N classification, tumor location, palliative resection, adjuvant treatment, chemotherapy, and radiation therapy were factors that showed survival difference between PR and NR. Regional lymph node metastasis (RR, 2.084; 95% CI, 1.491-2.914; p<0.001), non-resections (RR, 2.270; 95% CI, 1.497-3.443; p<0.001), and no chemotherapy (RR, 1.604; 95% CI, 1.095-2.349; p=0.015) were identified as risk factors for poor outcome on multivariate analysis.ConclusionsWithout evidence of systemic disease, palliative resection may provide some survival benefit in selected locally advanced unresectable EHCs and adjuvant treatment may further improve survival outcome.