Factors Associated with the Quality of Life among Family Caregivers of Cholangiocarcinoma Survivors in Northeastern Thailand.

BACKGROUND: Cholangiocarcinoma (CCA) is a common and usually lethal liver cancer especially in Southeast Asia. Family caregivers (FCs) and their quality of life (QOL) is important for the care process to operate effectively. However, there are only few research articles about the QOL of CCA FCs. The goal of this study was to assess the QOL and its associated factors among CCA FCs. MATERIAL AND METHODS: This cross-sectional study was undertaken with 231 CCA FCs who were the primary FCs for CCA patients in a tertiary hospital in Northeastern Thailand. The QOL was measured using the Thai version of the World Health Organization's Quality of Life Questionnaire. Multivariate regression models were developed to investigate the predictors of the QOL, including the demographic characteristics, symptoms, anxiety and depression, and support care need. RESULTS: The CCA caregivers had moderate to high QOL for all of four domains: the mean score was 27.03 (SD=2.81) for physical, 23.13 (SD=2.81) for psychological, 11.32 (SD=1.08) for social relationships, and 28.08 (SD=2.81) for environment. Multivariable analysis shows that, symptoms, support care need, age and education level were significant predictors of FCs's QOL. Moreover. The QOL was lower in younger FCs (p<0.001). CONCLUSION: Symptoms, support care needs, age, and education level were associated with QOL among FCs for CCA patients. A holistic strategy that includes caregiver training, psychosocial therapies, and proper support may help these FCs for a better QOL.

Prognosis of Advanced Cholangiocarcinoma in the Palliative Care Setting: A Series of 201 Cases.

OBJECTIVE: Prognosis of cholangiocarcinoma is poor, and palliative treatment options are limited in China. This study aimed to analyze prognostic factors affecting survival in patients with advanced cholangiocarcinoma. METHODS: Clinical data on 201 consecutive patients with cholangiocarcinoma who received treatment at a single center from May 2014 to December 2018 were analyzed retrospectively. Survival curves were plotted using the Kaplan-Meier method. Survival analyses were performed using a log-rank test. RESULTS: For first-line therapy, the disease control rate was 56% (85/152) and the overall response rate was 16% (24/152). The total disease control rate was 34% (23/67) for second-line therapy. The median progression-free survival was 7 months, and the median overall survival was 17 months. Next-generation sequencing was performed for 59 patients. The most frequently mutated genes were TP53 and PI3KCA. No significant association was found between gene mutations and treatment response or survival. Of 5 patients with high levels of microsatellite instability, 4 (80%) were sensitive to anti-programmed death 1 antibodies and remained in partial remission at last follow-up. CONCLUSIONS: Macroscopic tumor characteristics, rather than gene mutations, determine the prognosis of advanced cholangiocarcinoma. High microsatellite instability may be a favorable predictor of response to immunotherapy for cholangiocarcinoma.

The Clinical Management of Cholangiocarcinoma in the United States and Europe: A Comprehensive and Evidence-Based Comparison of Guidelines.

BACKGROUND: The incidence of cholangiocarcinoma has doubled over the last 15 years with a similar rise in mortality, which provides the impetus for standardization of evidence-based care through the establishment of guidelines. METHODS: We compared available guidelines on the clinical management of cholangiocarcinoma in the United States and Europe, which included the National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), British Society of Gastroenterology (BSG) and the International Liver Cancer Association (ILCA) guidelines. RESULTS: There is discordance in the recommendation for biopsy in patients with potentially resectable cholangiocarcinoma and in the recommendation for use of fluorodeoxyglucose positron emission tomography scans. Similarly, the recommendation for preoperative biliary drainage for extrahepatic and perihilar cholangiocarcinoma in the setting of jaundice is inconsistent across all four guidelines. The BILCAP (capecitabine) and ABC-02 trials (gemcitabine with cisplatin) have provided the strongest evidence for systemic therapy in the adjuvant and palliative settings, respectively, but all guidelines have refrained from setting them as standard of care, given heterogeneity in the study cohorts and ABC-02's negative intention-to-treat results. CONCLUSIONS: Future progress in enhancing survivorship of patients with cholangiocarcinoma would likely entail improvements in diagnostic biomarkers and novel systemic therapies. Based on recent results from studies of targeted therapy, future iterations of the guidelines will likely incorporate molecular profiling.

Near-infrared photoimmunotherapy (NIR-PIT) on cholangiocarcinoma using a novel catheter device with light emitting diodes.

Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapy for cancers that uses NIR light and antibody-photosensitizer (IR700) conjugates. However, it is difficult to deliver NIR light into the bile duct for cholangiocarcinoma (CCA) from the conventional extracorporeal apparatus. Thus, in this study, we developed a dedicated catheter with light emitting diodes (LEDs) that supersedes conventional external irradiation devices; we investigated the therapeutic effect of NIR-PIT for CCA using the novel catheter. The new catheter was designed to be placed in the bile duct and a temperature sensor was attached to the tip of the catheter to avoid thermal burn. An anti-epidermal growth factor receptor (EGFR) antibody, Panitumumab-IR700 conjugate or anti-human epidermal growth factor receptor type 2 (HER2) antibody, Trastuzumab-IR700 conjugate, was used with EGFR- or HER2-expressing cell lines, respectively. The in vitro efficacy of NIR-PIT was confirmed in cultured cells; the capability of the new catheter for NIR-PIT was then tested in a mouse tumor model. NIR-PIT via the developed catheter treated CCA xenografts in mice. NIR-PIT had an effect in Panitumumab-IR700 conjugate- and Trastuzumab-IR700 conjugate-treated CCA cells that depended on the receptor expression level. Tumor growth was significantly suppressed in mice treated with NIR-PIT using the novel catheter compared with controls (P < .01). NIR-PIT was an effective treatment for EGFR- and HER2-expressing CCA cells, and the novel catheter with mounted LEDs was useful for NIR-PIT of CCA.

Patterns of Failure and the Need for Biliary Intervention in Resected Biliary Tract Cancers After Chemoradiation.

BACKGROUND: This study assessed patterns of failure and rates of subsequent biliary intervention among patients with resected biliary tract cancers (BTCs) including gallbladder carcinoma (GBC) and extra- and intrahepatic cholangiocarcinoma (eCCA and iCCA) treated with adjuvant chemoradiation therapy (CRT). METHODS: In this single-institution retrospective analysis of 80 patients who had GBC (n = 29), eCCA (n = 43), or iCCA (n = 8) treated with curative-intent resection and adjuvant CRT from 2007 to 2017, the median radiation dose was 50.4 Gy (range 36-65 Gy) with concurrent 5-fluorouracil (5-FU) chemotherapy. All but two of the patients received adjuvant chemotherapy. The 2-year locoregional failure (LRF), 2-year recurrence-free survival (RFS), and 2-year overall survival (OS), and univariate predictors of LRF, RFS, and OS were calculated for the entire cohort and for a subgroup excluding patients with iCCA (n = 72). The predictors of biliary interventions also were assessed. RESULTS: Of the 80 patients (median follow-up period, 30.5 months; median OS, 33.9 months), 54.4% had American Joint Committee on Cancer (AJCC) stage 1 or 2 disease, 57.1% were lymph node-positive, and 66.3% underwent margin-negative resection. For the entire cohort, 2-year LRF was 23.8%, 2-year RFS was  43.7%, and 2-year OS was 62.1%.  When patients with iCCA were excluded, the 2-year LRF was 22.6%, the 2-year RFS was 43.9%, and the 2-year OS was 59.2%. In the overall and subgroup univariate analyses, lymph node positivity was associated with greater LRF, whereas resection margin was not. Biliary intervention was required for 12 (63.2%) of the 19 patients with LRF versus 11 (18%) of the 61 patients without LRF (P < 0.001). Of the 12 patients with LRF who required biliary intervention, 4 died of biliary complications. CONCLUSIONS: The LRF rates remained significant despite adjuvant CRT. Lymph node positivity may be associated with increased risk of LRF. Positive margins were not associated with greater LRF, suggesting that CRT may mitigate LRF risk for this group. An association between LRF and higher rates of subsequent biliary interventions was observed, which may yield significant morbidity. Novel strategies to decrease the rates of LRF should be considered.

Cholangiocarcinoma: Diagnosis and Management.

Cholangiocarcinoma is a highly lethal biliary epithelial tumor that is rare in the general population but has increased rates in patients with primary sclerosing cholangitis (PSC). It is heterogenous, and management varies by location. No effective prevention exists, and screening is likely only feasible in PSC. Patients often present in an advanced state with jaundice, weight loss, and cholestatic liver enzymes. Diagnosis requires imaging with magnetic resonance cholangiopancreatography, laboratory testing, and endoscopic retrograde cholangiopancreatography. Potentially curative options include resection and liver transplant with neoadjuvant or adjuvant chemoradiation. Chemotherapy, radiation, and locoregional therapy provide some survival benefit in unresectable disease.

Bio-engineered cell membrane nanovesicles as precision theranostics for perihilar cholangiocarcinoma.

Perihilar cholangiocarcinoma (PHCC) presents a formidable challenge due to its occult anatomic location, aggressive growth, insensitivity to conventional chemotherapy, and poor prognosis. Herein, we engineered a human epidermal growth factor receptor 2 (HER2) affibody to the surface of cell membrane nanovesicles (A-NVs) in a ligand-oriented manner and loaded them with indocyanine green (ICG) as precision theranostics for PHCC treatment. The A-NVs@ICG were prepared and exhibited satisfactory targeting effects in HER2-overexpressing PHCC cells. In vivo fluorescence and photoacoustic imaging demonstrated that A-NVs@ICG promoted the accumulation of ICG in PHCC tissue, leading to enhanced tumor regression and improved anti-cancer effects when combined with photoirradiation. Therefore, bio-engineered A-NVs@ICG represent a promising nanotheranostic agent for PHCC with potential for clinical translation.

Prolonged Response to Anti-PD-1 Antibody Therapy in Chemotherapy-Refractory Cholangiocarcinoma With High Tumor Mutational Burden.

Management of advanced intrahepatic cholangiocarcinoma (iCCA) is challenging and overall survival is poor. Progress in the development of new therapeutic options for metastatic cholangiocarcinoma (CCA) has been slow; hence, to date, there are no approved second-line agents in this setting. Although the development of immune checkpoint inhibitors has significantly improved overall survival in a variety of malignancies, there has not been a clinically important impact in CCA. This report presents a 66-year-old patient with chemotherapy-refractory iCCA who experienced a prolonged response to immunotherapy. Tumor genome profiling revealed a high tumor mutation burden of 17 mutations per megabase in the absence of microsatellite instability. He was started on immunotherapy with nivolumab and has experienced an ongoing response for 16 months without clinical symptoms and only minimal radiologic disease.

The Effect of Nutrition Intervention with Oral Nutritional Supplements on Pancreatic and Bile Duct Cancer Patients Undergoing Chemotherapy.

Chemotherapy may negatively affect nutritional status and quality of life (QOL) in pancreatic cancer patients. Our aim was to investigate the beneficial effects of oral nutrition supplements (ONS) on pancreatic and bile duct cancer patients undergoing chemotherapy. Among patients with progressive pancreatic and bile duct cancer receiving chemotherapy, the ONS group (n = 15) received two packs of ONS daily for 8 weeks while the non-ONS group (n = 19) did not. Anthropometric measures, dietary intake, nutritional status, and quality of life were assessed. ONS significantly increased daily intakes of energy, carbohydrates, proteins, and lipids at 8 weeks compared to the baseline. After 8 weeks, fat mass significantly increased in the ONS group. For patients in their first cycle of chemotherapy, body weight, fat-free mass, skeletal muscle mass, body cell mass, and fat mass increased in the ONS group but decreased in the non-ONS group. Fat mass increased in second or higher cycle only in the ONS group. Patient-generated subjective global assessments (PG-SGA) and fatigue scores in the Quality of Life Questionnaire Core 30 (QLQ-C30) improved in the ONS group. ONS might improve nutritional status by increasing fat mass and/or maintaining the body composition of pancreatic and bile duct cancer patients with chemotherapy, especially those in the first cycle, and alleviate fatigue symptoms.

Percutaneous Portal Vein Embolization Using a Simplified Sheathless 18-Gauge Trocar Needle Approach: Review of Efficacy and Safety.

PURPOSE: Portal vein (PV) embolization (PVE) is traditionally performed via a PV sheath with selective embolization of PV branches. Here, the efficacy and safety of PVE with the use of only an 18-gauge needle is reported. MATERIALS AND METHODS: Consecutive patients who underwent PVE from 2009 through 2017 were retrospectively reviewed. Forty-five patients (mean age, 60 y ± 7.6; 38 men) underwent 45 PVE procedures. Hepatocellular carcinoma, cholangiocarcinoma, and metastases accounted for 26 (58%), 13 (29%), and 6 (13%) patients, respectively. PVE was performed by puncturing a branch of right PV with an 18-gauge needle under US guidance. Via the same needle, direct portography was performed, followed by PVE with an N-butyl cyanoacrylate/Lipiodol mixture. Percentage increase of future liver remnant (FLR) volume and increase in ratio of FLR to total liver volume were estimated as measures of efficacy. Complications were reported according to Society of Interventional Radiology classification. Fluoroscopy time, procedure time, and dose-area product (DAP) were recorded. RESULTS: Technical success rate was 100%. The median DAP, fluoroscopy time, and procedure time were 74,387 mGy·cm2 (IQR, 90,349 mGy·cm2), 3.5 min (IQR, 2.10 min), and 24 min (IQR, 10.5 min). Among the 23 patients with complete CT volumetry data, mean increase in the ratio of FLR to total liver volume and percentage increase of FLR volume were 12.5% ± 7.7 and 50% ± 33, respectively. There were 3 minor complications (asymptomatic nonocclusive emboli in FLR) and 3 major complications (1 hepatic vein emboli, 1 subphrenic collection, and 1 hepatic infarct). CONCLUSIONS: PVE via a sheathless 18-gauge needle approach is feasible, with satisfactory FLR hypertrophy.

Cytoreductive surgery and HIPEC improve survival compared to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups.

BACKGROUND: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. OBJECTIVE: To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. MATERIAL AND METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. RESULTS: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. CONCLUSION: Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.

High expression of MMP-9 is associated with better prognosis in extrahepatic bile duct cancer patients.

PURPOSE: To evaluate the prognostic value of matrix metalloproteinase-9 (MMP-9) in patients with extrahepatic bile duct (EHBD) cancer undergoing surgical resection and adjuvant radiotherapy. METHODS: Between January 2000 and August 2006, patients who underwent complete resection followed by adjuvant radiotherapy for EHBD cancer were enrolled in this study. The expression of MMP-9 was assessed with immunohistochemical staining. The prognostic values of the MMP-9 expression and other clinicopathologic factors were evaluated in univariate and multivariate analyses. RESULTS: Sixty-six patients were included in this study. All received radiotherapy with a median dose of 40 Gy (range, 40-56), and 61 patients received concomitant fluoropyrimidine chemotherapy. MMP-9 was highly expressed in 33 patients (50.0%). MMP-9 expression was significantly associated with locoregional recurrence-free survival (LRRFS) and overall survival (OS) but not with distant metastasis-free survival (DMFS). The 5-year LRRFS and OS rates were 50.8% versus 86.5% (p = .0281), and 23.3% versus 68.1% (p = .0087) in patients with low and high expression of MMP-9, respectively. Among the clinicopathologic factors, tumor location was associated with DMFS and OS (p = .0292 and .0003, respectively). Nodal stage and histologic differentiation showed significant association with DMFS (p = .0277 and .0060, respectively). Based on multivariate analysis for OS, tumor location was the only significant prognostic factor (p = .0021), while MMP-9 expression showed marginal significance (p = .0633). CONCLUSION: MMP-9 expression is a useful prognostic factor for predicting LRRFS and OS in patients with EHBD cancer after surgical resection and adjuvant radiotherapy.

Patient With Unresectable Cholangiocarcinoma Treated With Radiofrequency Hyperthermia in Combination With Chemotherapy: A Case Report.

Hyperthermia, which is a noninvasive treatment that causes tumor cells to become heated and that works in synergy with anticancer drugs and radiation therapy, is emerging as a promising treatment for patients with cancer. The purpose of this study is to report the efficacy of hyperthermia combined with chemotherapy (gemcitabine/cisplatin) for the treatment of a patient with unresectable cholangiocarcinoma. A 54-year-old man was diagnosed as hilar cholangiocarcinoma (Klatskin tumor) and was administered neoadjuvant and preoperative radiation with chemotherapy. However, because the treatment with radiation and chemotherapy was not successful, he decided to undergo hyperthermia combined with chemotherapy as a second treatment option. He was suffering from fatigue, dyspepsia, epigastralgia, and jaundice. Hyperthermia combined with chemotherapy was administered 32 times over a period of 4 months. The patient experienced no critical complications, and the patient's condition improved, with the carbohydrate antigen 19-9 (CA 19-9) and the total bilirubin levels being relatively lowered. In addition, the computed tomography scan showed that the cholangiocarcinoma had not progressed. In conclusion, this case report suggests radiofrequency hyperthermia combined with chemotherapy may be a promising treatment option for patients with unresectable cholangiocarcinoma.

Adjuvant concurrent chemoradiotherapy with low-dose daily cisplatin for extrahepatic bile duct cancer.

PURPOSE: We aimed to present the clinical outcomes of adjuvant concurrent chemoradiotherapy (CCRT) with low-dose daily cisplatin regimen compared to the conventional 5-fluorouracil (5-FU)-based regimen for extrahepatic bile duct cancer (EHBDC). METHODS: From October 1994 to April 2013, 41 patients received adjuvant CCRT with low-dose daily regimen or 5-FU-based regimens. Nineteen patients received low-dose of cisplatin just before every delivery of radiation therapy, and 21 patients received two cycles of 5-FU-based regimen during radiotherapy. We compared the clinical outcomes between two adjuvant CCRT regimens. RESULTS: Adjuvant CCRT with low-dose daily cisplatin showed comparable toxicity profiles compared with that of a 5-FU-based regimen. The median follow-up time was 33 months (range, 5-205), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 34.2, 50.8, and 49.7%, respectively. Univariable analyses showed no significant differences in OS, LRRFS, and DMFS between the groups with two regimens. In multivariable analyses, chemotherapeutic regimen was a significant prognostic factor for OS, favoring the low-dose daily cisplatin regimen (HR = 2.491, p = 0.036) over 5-FU-based regimen, though not for LRRFS (p = 0.642) and DMFS (p = 0.756). CONCLUSIONS: Adjuvant CCRT with low-dose daily cisplatin regimen showed acceptable toxicities and survivals compared to those of the 5-FU-based regimen. Low-dose daily cisplatin can be one of the feasible regimens for adjuvant CCRT for EHBDC.

Regional thermochemotherapy versus hepatic arterial infusion chemotherapy for palliative treatment of advanced hilar cholangiocarcinoma: a retrospective controlled study.

OBJECTIVES: To retrospectively assess the efficacy of regional thermochemotherapy (TCT) compared with hepatic arterial infusion chemotherapy (HAIC)-alone for palliative treatment of advanced hilar cholangiocarcinoma (HC) and to determine the prognostic factors associated with survival. METHODS: Forty-three consecutive patients with advanced HC underwent regional TCT (TCT group) and HAIC (HAIC group). We analyzed baseline characteristics, overall survival (OS), progression-free survival (PFS), stent patency time (SPT), adverse events (AEs), and prognostic factors for OS between the two groups. RESULTS: OS of patients treated with regional TCT was significantly longer compared to that of patients treated with HAIC (median OS: 20.3 vs. 13.2 months, P = 0.004), and SPT and PFS were significantly increased in the TCT group compared with the HAIC group (median SPT: 26.5 vs. 10.5 months, P < 0.001; median PFS: 16.5 vs. 10.2 months, P = 0.001). TCT and metal stent insertion were two independent prognostic factors associated with survival. The treatment-related AEs were tolerable and similar in the two groups, except for hilar pain (34.6 %) and skin rashes (24.6 %) in the TCT group. CONCLUSIONS: Our results show that regional TCT is safe and more effective than HAIC-alone and may be a promising option for palliative treatment of advanced HC. Metal stenting before TCT appears to improve patients' OS. KEY POINTS: • Regional TCT is a novel combination for palliative treatment of advanced HC • Our data showed significantly promising outcomes in the TCT group • HC patients with metal stenting appeared to derive greater benefit from TCT.

Outcome of Transplant-fallout Patients With Unresectable Cholangiocarcinoma.

OBJECTIVES: The aim of this was to determine survival after starting neoadjuvant therapy for patients who became ineligible for orthotopic liver transplantation (OLT). METHODS AND MATERIALS: Since January 1993, 215 patients with unresectable cholangiocarcinoma began treatment with planned OLT. Treatment included external-beam radiation therapy (EBRT) with fluorouracil, bile duct brachytherapy, and postradiotherapy fluorouracil or capecitabine before OLT. Adverse findings at the staging operation, death, and other factors precluded OLT in 63 patients (29%), of whom 61 completed neoadjuvant chemoradiation. RESULTS: By October 2012, 56 (89%) of the 63 patients unable to undergo OLT had died. Twenty-two patients (35%) became ineligible for OLT before the staging operation, 38 (60%) at the staging operation, and 3 (5%) after staging. From the date of diagnosis, median overall survival was 12.3 months. Survival was 17% at 18 months and 7% at 24 months. Median survival after fallout was 6.8 months. Median survival after the staging operation was 6 months. Two patients lived for 3.7 and 8.7 years before dying of cancer or liver failure caused by persistent biliary stricture at the site of the original cancer, respectively. Univariate analysis showed that time from diagnosis to fallout correlated with overall survival (P=0.04). CONCLUSIONS: In highly selected patients initially suitable for OLT, the mortality rate for cholangiocarcinoma was high in patients who became ineligible for OLT. Their survival, however, was comparable to expected survival for patients with locally advanced or metastatic disease treated with nontransplant therapies. The most common reason for patient fallout was adverse findings at the staging operation.

Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy. RESULTS: Increased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II. METHODS: The expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1ß dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy. CONCLUSIONS: HIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas.

[Efficacy of Combined Therapy(Drainage of the Bile Duct, High-Dose Hepatic Artery Infusion, and Radiation)for Hilar Cholangiocellularcarcinoma with Complete Portal Vein Obstruction].

We reported a case of hilar cholangiocellularcarcinoma with complete obstruction of the portal vein. The patient, who was a 65-year-old woman, suffered from fever and general fatigue as a result of acute cholangitis after insertion of a tube stent into the right bile duct. The main tumor was present on the right side of S1 and spread to both sides of the bile duct. S1 lobe was swollen and diffuse intrahepatic invasion was noted in the right lobe and S1. The portal vein was completely obstructed at the porta hepatis with a coronary vein-left renal vein shunt. We immediately administered a high-dose hepatic arterialinfusion( 5-FU 1 g×3 days: one day off 1 g×3 days)(HDHAI)to the right hepatic artery using a transient catheter insertion method. After 2 courses of HDHAI, the intrahepatic invasion decreased. However, after 4 courses of HDHAI(2 on the right side and 2 on the left side), the invasion on the left side of the IVC had increased. We then chose radiation therapy. Subsequently, transient cystic changes were observed; however, 4 months after radiation, the invasion on the left side of the IVC had regrown into the cardia. The patient suffered from vomiting as a result of the narrowing of the esophagus. We chose HDHAI and dilation of the esophagus using a balloon. Finally, the invasion on the left side of the IVC and S1 swelling decreased, and she could eat again. Thirteen months later, she remains an outpatient. We recommend HDHAI and radiation therapy to hilar cholangiocellularcarcinoma even if the portal vein is completely obstructed.