PURPOSE: Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain. MATERIALS AND METHODS: Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS). RESULTS: Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320). CONCLUSION: sGemCis maintenance is not associated with an improved survival outcome.
Biliary Tract Neoplasms ; Biliary Tract ; Cholangiocarcinoma ; Chungcheongnam-do ; Cisplatin ; Disease-Free Survival ; Drug Therapy ; Humans ; Korea ; Retrospective Studies ; Seoul

Cholangiocarcinoma is the most common biliary malignancy and the second most common hepatic malignancy following hepatocellular carcinoma. It can be classified anatomically as intrahepatic cholangiocarcinoma (iCCA), perihilar CCA, or distal CCA. The treatment of choice for iCCA is surgical resection, but only those with potentially resectable tumors can undergo surgery. The standard regimen for advanced stage iCCA is gemcitabine and cisplatin. We encountered two unusual cases of iCCA patients who were initially diagnosed as unresectable cases and underwent systemic chemotherapy, which showed great response and therefore enabled radical operation. The patients show that even though iCCA is a challenging disease, patients with good response to chemotherapy may have a chance to undergo radical surgery.
Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Cisplatin ; Drug Therapy ; Humans

PURPOSE: Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC. MATERIALS AND METHODS: Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue. RESULTS: In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07). CONCLUSION: OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.
Biliary Tract Neoplasms* ; Biliary Tract* ; Cholangiocarcinoma ; Cisplatin ; Diarrhea ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination ; Exome ; Humans ; Male ; Neutropenia ; Peripheral Nervous System Diseases ; Prognosis ; Triplets

The term of biliary tract cancer (BTC) refers to all tumors that arise from the biliary tract or the biliary drainage system, including the intra- and extra-hepatic bile ducts as well as the gallbladder. BTCs are aggressive tumors with limited treatment options and poor overall survival. Currently, surgery remains to be the only potentially curative treatment, and most patients develop recurrence. For advanced tumors, only limited effective treatment modalities exist today. Gemcitabine plus cisplatin is considered as a standard option for advanced biliary cancer. A randomized phase III trial (ABC-02 trial) showed superiority of gemcitabine plus cisplatin over gemcitabine alone. In that study, they showed that after a median follow-up of 8.2 months, the median overall survival was 8.1 months in the gemcitabine-only group and 11.7 months in the gemcitabine plus cisplatin group (p<0.001). However, while this is a definite advancement, a 3-month survival extension among patients with BTC is modest at best. Moreover, this regimen has not been compared head-to-head with other gemcitabine based combinations. Gemcitabine monotherapy, 5-fluorouracil plus leucovorin, and single-agent capecitabine are all reasonable options for patients with a borderline performance status. Recent advancements have provided new insight into the genomic landscape of BTCs, and thus, it remains unclear whether combined treatment with molecular targeted agents or other cytotoxic chemotherapeutic agents may also be effective against advanced BTC.
Bile Ducts ; Biliary Tract Neoplasms* ; Biliary Tract* ; Capecitabine ; Cholangiocarcinoma ; Cisplatin ; Drainage ; Drug Therapy* ; Fluorouracil ; Follow-Up Studies ; Gallbladder ; Humans ; Leucovorin ; Recurrence

A 54-year-old female with postprandial dyspepsia and abdominal pain was diagnosed as locally advanced unresectable intrahepatic cholangiocarcinoma by radiologic imaging studies resulting in invasion to bilateral main bile duct and right portal vein. The patient underwent extended right hepatectomy and portal vein resection after gemcitabine and cisplatin combined chemotherapy for a total of 40 cycles after the diagnosis. Final pathology showed, followed by pathological complete remission, without any residual cancer cell. The patient has survived for over 6 years without any evidence of recurrence. This case suggests that locally advanced intrahepatic cholangiocarcinoma, which can't be resected, was also proved to be capable of pathological complete remission with active chemotherapy, and long-term survival could be achieved. Therefore, active multidisciplinary approach and patient-oriented treatments using various methods should be considered for locally advanced unresectable intrahepatic cholangiocarcinoma.
Abdominal Pain ; Bile Duct Neoplasms ; Bile Ducts ; Cholangiocarcinoma* ; Cisplatin ; Diagnosis ; Drug Therapy* ; Dyspepsia ; Female ; Hepatectomy ; Humans ; Middle Aged ; Neoplasm, Residual ; Pathology ; Portal Vein ; Recurrence

Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a primary liver cancer with histopathologic features of both hepatocelluar carcinoma and cholangiocarcinoma. As combined HCC-CC has been associated with poor outcomes, accurate diagnosis and proper treatment planning for patients are considered to be important for improving survival. Currently, surgery is known as the only treatment modality offering potential cure for localized disease. However, there are little published treatment options for advanced or recurrent disease. Furthermore, no published reports exist in respect to the applying successful curative resection after neoadjuvant therapy for advanced combined HCC-CC. Here, we report a case of combined HCC-CC subtype with stem cell feature, intermediate type who underwent curative surgical resection after neoadjuvant chemotherapy consisting of cisplatin and gemcitabine. Pathologic report revealed negative resection margin and follow-up imaging study shows no evidence of tumor recurrence.
Cholangiocarcinoma ; Cisplatin ; Diagnosis ; Drug Therapy* ; Follow-Up Studies ; Humans ; Liver Neoplasms ; Neoadjuvant Therapy ; Recurrence ; Stem Cells

BACKGROUND/AIMS: Standard treatments are not available for hilar nonresectable cholangiocarcinoma (NCC). It is unknown whether combination therapy of photodynamic therapy (PDT) plus systemic chemotherapy is superior to PDT alone. METHODS: We retrospectively reviewed 68 patients with hilar NCC treated with either PDT plus chemotherapy (PTD-C) or PDT monotherapy (PDT-M). The primary endpoint was the mean overall survival rate. Secondary endpoints included the 1-year survival rate, risk of cholangitic complications, and outcomes, which were evaluated according to the chemotherapy protocol. RESULTS: More than 90% of the study population had advanced hilar NCC Bismuth type III or IV. In the PDT-M group (n=35), the mean survival time was 374 days compared with 520 days in the PDT-C group (n=33, p=0.021). The 1-year survival rate was significantly higher in the PDT-C group compared with the PDT-M group (88% vs 58%, p=0.001) with a significant reduction of mortality (hazard ratio, 0.20; 95% confidence interval, 0.07 to 0.58; p=0.003). Gemcitabine monotherapy resulted in a shorter survival time compared with the gemcitabine combination therapy (mean, 395 days vs 566 days; p=0.09). Cholangitic complications were observed at a similar frequency in the PDT-C and PDT-M groups. CONCLUSIONS: Combining repeated PDT with a gemcitabine-based combination therapy might offer a significant survival benefit in patients with hilar NCC.
Bismuth ; Cholangiocarcinoma* ; Drug Therapy* ; Humans ; Mortality ; Photochemotherapy* ; Retrospective Studies ; Survival Rate

PURPOSE: This study analyzed the outcomes of patients with resected extrahepatic bile duct cancer (EHBDC) in order to clarify the role of adjuvant treatments in these patients. MATERIALS AND METHODS: A total of 336 patients with EHBDC who underwent curative resection between 2001 and 2010 were analyzed retrospectively. The treatment types were as follows: surgery alone (n=168), surgery with chemotherapy (CTx, n=90), surgery with radiotherapy (RT) alone (n=29), and surgery with chemoradiotherapy (CRT, n=49). RESULTS: The median follow-up period was 63 months. The 5-year rates of locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for all patients were 56.5%, 59.7%, 36.6%, and 42.0%, respectively. In multivariate analysis, surgery with RT and CRT was a significant prognostic factor for LRFFS, and surgery with CTx was a significant prognostic factor for DMFS, and surgery with CTx, RT, and CRT was a significant prognostic factor for PFS (p < 0.05). Surgery with CTx and CRT showed association with superior OS (p < 0.05), and surgery with RT had marginal significance (p=0.078). In multivariate analysis of the R1 resection patients, surgery with CRT showed significant association with OS (p < 0.05). CONCLUSION: Adjuvant RT and CTx may be helpful in improving clinical outcomes of patients with resected EHBDC who have a high risk of disease recurrence, particularly R1 resection patients. Conduct of additional prospective, larger-scale studies will be required in order to confirm the benefit of adjuvant RT and CTx in these patients.
Bile Ducts, Extrahepatic* ; Biliary Tract Neoplasms ; Chemoradiotherapy ; Cholangiocarcinoma ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Prospective Studies ; Radiotherapy* ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Treatment Outcome*

Cholangiocarcinoma with paraneoplastic dermatomyositis (DM) is extremely rare, and the whole body positron emission tomography-computed tomography (PET-CT) finding of paraneoplastic DM is rarely reported. We report a 66-year-old woman with metastatic cholangiocarcinoma, initially presented with bilateral proximal muscle uptake on PET-CT without clinical muscle symptoms. The initial interpretation of the high muscle uptake was metastasis to the muscles. However, while awaiting for chemotherapy, muscle weakness evolved and rapidly progressed. The level of creatine phosphokinase was significantly elevated. Electromyography revealed moderate myopathy, and a muscle biopsy showed degenerating myofibers with variable sizes. The diagnosis of paraneoplastic dermatomyositis was made. This case highlights that, although rare, paraneoplastic dermatomyositis can be present with cholangiocarcinoma. Also, muscle inflammation can precede the clinical muscle symptoms, and paraneoplastic DM should be considered as a possible differential diagnosis in the assessment of cancer patients who present with abnormal muscle tracer uptake in PET-CT scans.
Aged ; Biopsy ; Cholangiocarcinoma* ; Creatine Kinase ; Dermatomyositis* ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Electromyography ; Electrons* ; Female ; Humans ; Inflammation ; Muscle Weakness ; Muscles ; Muscular Diseases ; Neoplasm Metastasis ; Positron-Emission Tomography

Cholangiocarcinoma with paraneoplastic dermatomyositis (DM) is extremely rare, and the whole body positron emission tomography-computed tomography (PET-CT) finding of paraneoplastic DM is rarely reported. We report a 66-year-old woman with metastatic cholangiocarcinoma, initially presented with bilateral proximal muscle uptake on PET-CT without clinical muscle symptoms. The initial interpretation of the high muscle uptake was metastasis to the muscles. However, while awaiting for chemotherapy, muscle weakness evolved and rapidly progressed. The level of creatine phosphokinase was significantly elevated. Electromyography revealed moderate myopathy, and a muscle biopsy showed degenerating myofibers with variable sizes. The diagnosis of paraneoplastic dermatomyositis was made. This case highlights that, although rare, paraneoplastic dermatomyositis can be present with cholangiocarcinoma. Also, muscle inflammation can precede the clinical muscle symptoms, and paraneoplastic DM should be considered as a possible differential diagnosis in the assessment of cancer patients who present with abnormal muscle tracer uptake in PET-CT scans.
Aged ; Biopsy ; Cholangiocarcinoma* ; Creatine Kinase ; Dermatomyositis* ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Electromyography ; Electrons* ; Female ; Humans ; Inflammation ; Muscle Weakness ; Muscles ; Muscular Diseases ; Neoplasm Metastasis ; Positron-Emission Tomography