s-1-(combination) and Bile-Duct-Neoplasms

A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach-preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of the liver. The patient received 2 courses of gemcitabine-cisplatin combination chemotherapy. No new lesions were detected after chemotherapy and the patient underwent a partial liver resection of segment 8. The pathological examination revealed a metachronous distant metastasis originating from the bile duct carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6 months. Following completion of all therapies, the patient survived without tumor recurrence for 3 years and 10 months after the initial operation. Thus, surgical interventions might be effective in improving prognosis among selected patients with postoperative liver metastasis of bile duct carcinoma.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cisplatin; Deoxycytidine; Drug Combinations; Gemcitabine; Hepatectomy; Humans; Liver Neoplasms; Male; Oxonic Acid; Pancreaticoduodenectomy; Tegafur

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.).

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Cholangiocarcinoma; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Prospective Studies; Radiofrequency Ablation; Tegafur; Treatment Outcome

Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50-0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27-0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9<466 U/ml were more responsive to chemotherapeutic agents than those with CA19-9≥571 U/ml (88.9% vs 0%, P<0.001). We conclude that the combination of GEM plus S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; CA-19-9 Antigen; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Klatskin Tumor; Male; Middle Aged; Oxonic Acid; Tegafur

Hilar cholangiocarcinoma is an uncommon cancer and its overall incidence is increasing. Photodynamic therapy (PDT) has been proposed as palliative management for unresectable hilar cholangiocarcinoma (UHC). To date, little is known about the role of the addition of systemic chemotherapy to PDT for UHC. We performed a prospective, randomised, phase II trial to compare PDT plus S-1 and PDT alone for UHC.. Patients with UHC were randomly assigned (in a 1:1 ratio) to PDT plus S-1 or PDT alone. The primary end-point was overall survival. The secondary end-points were progression-free survival, complications, re-intervention rate and quality of life. This trial is registered with clinicalTrials.gov, number NCT00869635.. Between February 2009 and May 2012, we randomly assigned 21 patients to receive PDT plus S-1 and 22 to receive PDT alone. The UHC patients treated with PDT plus S-1 showed higher 1-year survival rate compared with the patients treated with PDT alone (76.2% versus 32%, P=0.003) and prolonged overall survival (median 17 months, 95% confidence interval [CI]: 12.6-21.4, versus 8 months, 95% CI: 6-10, P=0.005, hazard ratio [HR], 0.36; 95% CI: 0.17-0.75). Regarding the secondary end-points, PDT plus S-1 was associated with prolonged progression-free survival compared with PDT alone (median 10 months [95% CI: 4.1-16] versus 2 months [95% CI: 0.4-3.5], P=0.009 (HR for progression 0.39, 95% CI: 0.19-0.83). There were no differences in the number of PDT sessions, the frequency of cholangitis, overall adverse events or the quality of life in either group.. PDT plus S-1 was well tolerated and was associated with a significant improvement of overall survival and progression-free survival compared with PDT alone in patients with UHC. These findings warrant further clinical investigation of PDT plus S-1 in patients with UHC.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Bile Duct Neoplasms; Cholangiocarcinoma; Combined Modality Therapy; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Photochemotherapy; Prospective Studies; Pyrimidines; Quality of Life; Retreatment; Survival Analysis; Tegafur; United States

Pancreatobiliary tract cancers are amongst the most aggressive human cancers. Histone deacetylase (HDAC) is well-known to be associated with tumorigenesis through epigenetic regulation and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We conducted a clinical trial of combination therapy using valproic acid (VPA, a HDACI) and S-1, which is an oral fluoropyrimidine derivative consisting of 5-fluorouracil.. Patients with advanced pancreatobiliary tract cancers were eligible for this clinical trial. Twelve patients, in whom a curative operation was not feasible, were enrolled in the study. Patients received S-1 orally at a daily dose of 80 mg/m(2) for 28 days, followed by a 14-day recovery period. They also received VPA orally at a total daily dose of 15 mg/kg, twice daily.. One patient had partial response (PR); ten patients were recorded with stable disease (SD); and one patient showed progressive disease (PD). Eight patients had clinically significant drug-related adverse events. The most frequent adverse events were platelet depletion and fatigue. Grade 3/4 adverse events, including anemia and platelet depletion, were observed. Significant increases in blood concentrations of VPA were confirmed 2 and 4 weeks after VPA administration.. Combination therapy of VPA and S-1 for patients with pancreatobiliary tract cancers had a manageable safety profile and preliminary antitumor activity.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Drug Combinations; Female; Histone Deacetylases; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Tegafur; Treatment Outcome; Valproic Acid

Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial.. Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events.. One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing.. UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Bile Duct Neoplasms; Carcinoma; Cholangiocarcinoma; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Gallbladder Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Prospective Studies; Tegafur; Treatment Outcome

A 68-year-old man underwent a subtotal stomach-preserving pancreatoduodenectomy(SSPPD)for a distal bile duct carcinoma(BDC)pT3aN1M0, pStage ⅡB and adjuvant chemotherapy with gemcitabine. One year 7 months after the initial surgery, CT revealed a nodule with an increasing tendency in the left lung. As it was difficult to distinguish primary lung cancer from BDC lung metastasis, we performed a thoracoscopic left wedge resection. The histopathology of the resected specimen was BDC lung metastasis. In the follow-up with adjuvant chemotherapy with S-1 for 10 months, 2 nodules were found in the right lung, and we performed thoracoscopic right S6 segmentectomy. Eight months later, another nodule was found in the left lung, and we performed thoracoscopic left wedge resection. The histopathology was BDC lung metastasis for all the resected specimens. The patient is alive with no evidence of recurrence after 9 months of the latest surgery(4 years 11 months after the initial surgery). Although the standard treatment for metastatic recurrence of BDC is systemic chemotherapy, some cases treated with surgical resection had relatively good prognosis, such as the present case. Surgical resection might be feasible as a treatment option for metastatic recurrence of BDC.

Topics: Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts; Drug Combinations; Humans; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pancreaticoduodenectomy; Pneumonectomy; Tegafur

To improve the prognosis of cholangiocarcinoma, we investigated potential biomarkers that may enable the selection of patients for whom postoperative adjuvant chemotherapy is likely effective.. The cohort of this retrospective study included 170 surgically resected cholangiocarcinoma patients, 26 with gemcitabine adjuvant chemotherapy (GEM group), 36 with S-1 adjuvant chemotherapy (S-1 group), and 103 receiving no adjuvant chemotherapy (NC group). Propensity score matching was performed to adjust patient backgrounds; 36 patients from the NC group then were selected. Immunohistochemistry of orotate phosphoribosyltransferase (OPRT) and human equilibrative nucleoside transporter 1 (hENT1) was performed to determine the correlation between their expression and disease-free survival (DFS).. After matching, the backgrounds of these three groups were unbiased. No significant improvement of DFS by adjuvant chemotherapy was observed in the whole cohort. However, among the high-OPRT-expression patients, DFS of GEM, S-1, and NC groups at 5 years was 28.8%, 53.8%, and 25.5%, respectively. The DFS of the S-1 group was significantly longer than that of the NC group (P = 0.034). On the other hand, no significant differences in DFS were observed among the low OPRT expression patients. hENT1 expression was shown to have no predictive value. Multivariate analysis of the high-OPRT-expression patients demonstrated that S-1 adjuvant chemotherapy can reduce tumor recurrence (HR, 0.303; P = 0.013).. Cholangiocarcinoma patients with high OPRT expression would benefit from postoperative adjuvant S-1 therapy, which increases the DFS. Assessment of OPRT expression may contribute to the optimization of adjuvant chemotherapy for cholangiocarcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cholangiocarcinoma; Cohort Studies; Drug Combinations; Equilibrative Nucleoside Transporter 1; Female; Gene Expression; Humans; Immunohistochemistry; Male; Orotate Phosphoribosyltransferase; Oxonic Acid; Predictive Value of Tests; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome

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.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Biomarkers, Tumor; Cell Nucleus; Chemotherapy, Adjuvant; Cholangiocarcinoma; Cytoplasm; Deoxycytidine; Disease-Free Survival; Drug Combinations; ELAV-Like Protein 1; Female; Gemcitabine; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur

Gallbladder cancer (GBC) is a highly fatal malignancy. Due to its invasiveness and delayed diagnosis, many GBC patients are diagnosed with synchronous liver and hepatoduodenal ligament involvement. In our case, we report a gallbladder cancer with portal vein thrombus.. A 60-year-old woman presented with persistent upper abdominal dull pain for 2 months.. Ultrasound examination showed gallbladder carcinoma invading liver segment IV, and a tumor thrombus in the left and right main portal trunk. Ultrasonography and contrast-enhanced magnetic resonance imaging (MRI) showed gallbladder carcinoma with invasion of adjacent liver, and tumor thrombus in the right branch of the portal vein and intrahepatic bile duct. Abdominal computed tomography angiography (CTA) revealed no hepatic artery invasion.. We made a decision to perform extended right lobectomy. Twenty-six days later, the patient underwent intravenous infusion port implantation for S-1 plus oxaliplatin (SOX) therapy.. After treatment, the patient has been doing very well and no recurrence has been found for 5 months.. The patient with gallbladder cancer and tumor thrombus in the portal vein described in this report provides a reminder for surgeons of the importance of early diagnosis, and adequate surgical and adjuvant treatment. Multi-disciplinary treatment is significantly beneficial for the overall survival of patients with advanced GBC.

Topics: Administration, Intravenous; Antineoplastic Agents; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Drug Combinations; Female; Gallbladder Neoplasms; Hepatectomy; Hepatic Artery; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Middle Aged; Neoplasm Invasiveness; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Portal Vein; Tegafur; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Vascular Access Devices; Vascular Neoplasms

Cholangiocarcinoma (CCA) is one of the most difficult cancers to treat and lacks an established standard chemotherapy regimen. This study evaluated the effects of different combinations of gemcitabine, sorafenib, and S-1 on CCA cells to identify the optimal drug combination. A fractional factorial design method was applied in drug combination experiments to determine the optimal combination of these three drugs (gemcitabine=1.4 mmol/l, sorafenib=0.03 mmol/l, S-1=0.185 mmol/l). We constructed a mathematical model with a small number of runs (Y=1.14-0.377A-23.0B-1.81C+0.084A+109B+6.06C+3.83AB+0.175AC-40.4BC) to predict the efficacy of combinations of the drugs. The optimal combination can significantly inhibit the AKT/mTOR pathway, and thus CCA cell proliferation, and can induce cell apoptosis. In vivo, this combination (gemcitabine=1.4 mmol/l, sorafenib=0.03 mmol/l, S-1=0.185 mmol/l) can significantly inhibit tumor growth. The present study showed that the mathematical model was reliable and could predict the efficacy of the different drug combinations. The optimal combination of these drugs may aid the development of a promising standard chemotherapy regimen for CCA.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cell Line, Tumor; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Drug Screening Assays, Antitumor; Gemcitabine; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Models, Statistical; Niacinamide; Oxonic Acid; Phenylurea Compounds; Random Allocation; Sorafenib; Tegafur; Xenograft Model Antitumor Assays

We report curative resection of an advanced intrahepatic cholangiocarcinoma that responded well to combined S-1 and gemcitabine chemotherapy(GS therapy). A 67-year-old woman was admitted to our hospital in July 2011 for upper right abdominal pain. She was diagnosed with intrahepatic cholangiocarcinoma with abdominal para-aortic lymph node metastasis on the basis of the computed tomography (CT) findings. She was treated with GS therapy. One course of S-1(80 mg/m(3)) consisted of the administration of the drug for 14 days, followed by 14 days of rest; GEM(1,000 mg/m(3)) was administered on days 1 and 15 after initiating S-1. After 2 courses of treatment, the sizes of the primary tumor and the lymph node metastasis were observed to be reduced on CT. In September, partial hepatectomy and regional lymph node dissection were performed. The patient subsequently received 22 postoperative courses of GS therapy. The patient's postoperative course was uneventful, and she remains free of recurrence 49 months since diagnosis. Therefore, GS therapy is a possible option for the management of advanced intrahepatic cholangiocarcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Hepatectomy; Humans; Liver Neoplasms; Lymphatic Metastasis; Oxonic Acid; Tegafur; Treatment Outcome

The most common histological classification of bile duct cancer is adenocarcinoma and squamous cell carcinoma (SCC) is relatively rare. We report a case of a 78-year-old man with SCC of the extrahepatic bile duct associated with metachronous para-aortic lymph node metastasis. He had undergone subtotal stomach-preserving pancreatoduodenectomy. The pathological findings demonstrated moderately differentiated SCC of the distal extrahepatic bile duct (T1N1M0, stage IIB). 6 months after surgery, recurrence of the para-aortic lymph node was shown in abdominal CT. 5 courses of tegafur/gimeracil/oteracil (S-1) plus cisplatin therapy was performed and the para-aortic lymph node disappeared, confirmed as complete response by imaging findings. The patient is alive without recurrence, 10 months after recurrence and chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Carcinoma, Squamous Cell; Cholangiopancreatography, Endoscopic Retrograde; Cisplatin; Dose-Response Relationship, Drug; Drug Combinations; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasms, Second Primary; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

We report a case of lymph node metastasis of intrahepatic bile duct cancer that was successfully treated using chemotherapy and radiation therapy.A man in his 70s underwent hepatic resection for intrahepatic bile duct cancer, and abdominal CT 1 year 8 months after surgery revealed lymph node swelling(25mm in diameter)along the common hepatic artery.He was diagnosed with lymph node metastasis and began to receive chemotherapy.We administered gemcitabine(GEM), cisplatin, and S-1 for 6 months, and GEM and S-1 for 1 year 4 further months as combination therapy.One year 10 months after the start of chemotherapy, the size of the lymph node decreased to 13 mm.However, as FDG uptake was seen on FDG-PET, radiation targeted to the lymph node was applied(50 Gy/25 Fr).After completion of radiation therapy, the lymph node has not regrown even in the absence of treatment, and the patient survives 6 years after the primary operation(4 years 4 months since the start of chemotherapy for recurrence).This case suggested that multidisciplinary therapy might be useful for lymph node metastasis of intrahepatic bile duct cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Lymphatic Metastasis; Male; Oxonic Acid; Recurrence; Tegafur; Treatment Outcome

Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of the study was to evaluate the outcome of proton beam therapy (PBT) for patients with unresectable ICC.. Up to 2010, 20 patients (11 males, 9 females, median age 63 years old) with unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV, respectively) were treated with PBT. The largest dimensions of the tumors ranged from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17 fractions, respectively. Four patients received concurrent chemotherapy (tegafur, gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated curatively, and eight were treated palliatively because tumors were present outside the irradiation field.. In the curative group, nine tumors within the irradiated field were controlled in follow-up of 8.6-62.6 months (median: 20.8 months). Median survival rates in the curative and palliative groups were 27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were 82% and 38%, and 50% and 0%, respectively. Eight patients survived for > 2 years, and there was no distant metastasis in five of these patients after 2 years. No severe side-effects occurred.. The results suggest that long-term survival can be achieved using PBT for patients with unresectable ICC without distant metastasis. Further studies are required to determine the optimal treatment schedule and best combination of PBT and chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Combined Modality Therapy; Dose Fractionation, Radiation; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Proton Therapy; Radiotherapy Dosage; Survival Rate; Tegafur; Time Factors; Treatment Outcome

We report here a rare case of a patient with recurrent intrahepatic cholangiocarcinoma that was treated with simple S-1 chemotherapy, who is still alive 6 years later. A liver tumor was identified in segments 5 to 6 in a 60-year-old male asymptomatic hepatitis B carrier. The tumor was diagnosed as hepatocellular carcinoma by MRI and CT. However, following its resection by extended posterior segmentectomy of the liver, pathological findings identified it as an intrahepatic cholangiocarcinoma. The surgical margin was cancer-negative. No additional adjuvant chemotherapy was administered because of the patient 's impaired renal function. When tumor recurrence was found by MRI 30 months later, an additional liver resection was planned but a laparotomy was eventually performed. This was because intraoperative findings revealed Glissonian sheath invasion with involvement of the umbilical portion. S-1 treatment(100mg/body/day)was started. Although the dose had to be reduced(mostly 75mg/body/day)due to hyperbilirubinemia and there were some interruptions in the regimen, in total of 42 g of S-1 was administered. The patient is currently still alive, 6 years after the detection of the tumor recurrence. This represents a rare case in patients with intrahepatic cholangiocarcinoma.

Topics: Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Drug Combinations; Hepatectomy; Humans; Male; Middle Aged; Oxonic Acid; Recurrence; Tegafur; Time Factors

A 67-year-old man with elevated hepatobiliary enzymes was referred to our hospital for further examination. Computed tomography indicated hilar cholangiocarcinoma of Bismuth type Ⅳ and revealed invasion of the right hepatic artery and the left portal vein. We diagnosed locally advanced unresectable hilar cholangiocarcinoma, and performed 5 courses of chemotherapy with gemcitabine plus S-1. After chemotherapy, the tumor was significantly reduced in size and vascular invasions were alleviated, so we decided to perform surgical resection. An extended left hepatectomy with caudate lobe and extrahepatic bile duct resection was performed. Although the intraoperative pathological examination was positive for cancer at the hepatic margins, we did not perform further bile duct resection because of the difficulty. After the surgery, we administered adjuvant chemotherapy with gemcitabine for 5 courses. Another 8 courses of gemcitabine plus S-1 therapy were given because of elevation of CA19-9. The tumor marker levels normalized, and the patient is still alive without findings of recurrence 4 years after the first treatment. Multidisciplinary treatment with chemotherapy and surgery may suggest the possibility of increasing long term survival even for patients with locally advanced unresectable cholangiocarcinoma.

Topics: Aged; Antineoplastic Agents; Bile Duct Neoplasms; Cholangiocarcinoma; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Gemcitabine; Hepatectomy; Humans; Male; Oxonic Acid; Pancreatectomy; Tegafur; Time Factors; Treatment Outcome

We report of a patient with 3-year relapse-free survival after surgical resection for lung and liver metastases of distal cholangiocarcinoma (DCC). A quinquagenarianman was taken to a local hospital in October 2009 for yellow urine. He was diagnosed with DCC and was referred to our hospital for surgery. Pancreaticoduodenectomy was performed, and there was no residual tumor on histological examination. He did not receive any adjuvant therapy. One year 7 months after surgery, an isolated lung metastasis was identified on CT and was surgically removed. Six months after resection of the lung metastasis, a solitary liver metastasis was detected. Although systematic chemotherapy (gemcitabine plus S-1; 2 weeks treatment, 1 week drug free) was administered, the treatment was abandoned because of grade 3 (CTCAE v4.0) of skin disorders during the third course. Partial resection of the liver was performed in April 2012. Alternate-day treatment with S-1 was performed after resection of liver metastasis and is ongoing without adverse events. He has survived for more than 3 years without recurrence after liver resection. In this case of DCC metastasis, prognosis improved with surgical resection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Gemcitabine; Hepatectomy; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pancreaticoduodenectomy; Recurrence; Tegafur

An 80-year-old man with common bile duct cancer was treated by pancreaticoduodenectomy with D2 lymph node dissection in October 2005. The patient presented with frequent episodes of bloody-mucous rectal discharge in July 2009. An abdominal CT demonstrated local recurrence at the hepatoduodenal ligament. We treated him with concurrent chemoradiotherapy (CRT) with single-dose S-1 chemotherapy. After 6 months, we diagnosed a complete response (CR) by follow-up CT. The patient was treated with S-1 for 3 years after the diagnosis of a CR. He is alive without disease 6 years after the diagnosis of the recurrence. Concurrent CRT with S-1 chemotherapy may be the therapy of choice for recurrence of bile duct cancer.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Chemoradiotherapy; Drug Combinations; Humans; Male; Oxonic Acid; Pancreaticoduodenectomy; Recurrence; Tegafur

We report a 3-year survival case of cholangiocarcinoma treated with S-1 monotherapy despite positive margins after palliative bile duct resection. A 66 year-old man visited our hospital for jaundice. Because a smooth round defect was observed in the middle bile duct on ERCP, an impacted stone was suspected. Bile duct incision was performed, but the suspected stone was a tumor that was pathologically diagnosed as cholangiocarcinoma. Although pancreaticoduodenectomy was recommended, the patient decided to undergo palliative bile duct resection. Postoperative pathological examination showed moderately tubular adenocarcinoma with lymph node metastasis. The surgical margins of the hepatic side, duodenal side, and exfoliated surface were all positive. Subsequently, the patient chose to undergo S-1 monotherapy for maintaining his lifestyle. S-1 was orally administered at 100mg/day for 4 weeks, followed by 2 weeks of rest. He has continued S-1 monotherapy and survived for 3 years without evidence of recurrence.

Topics: Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Cholangiocarcinoma; Drug Combinations; Humans; Male; Oxonic Acid; Pancreaticoduodenectomy; Prognosis; Tegafur

It is sometimes difficult to differentiate between metastatic and primary liver tumors, when the liver tumor occurs simultaneously with a gastric cancer. We encountered a case of resected gastric cancer, which occurred concomitantly with intrahepatic cholangiocarcinoma after S-1 plus cisplatin chemotherapy, in a patient who was previously diagnosed with metastatic liver tumor before treatment. An 80-year-old man was admitted to our hospital because of epigastralgia. Endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper body of the stomach. A plain CT scan showed an irregular, low-density area, which was enhanced by contrast medium in the lateral segment of the liver. We performed an ultrasound- guided needle biopsy, because it was impossible to make a definitive diagnosis by dynamic CT, contrast-enhanced ultrasonography, and MRI. Immunohistochemical analysis for cytokeratin 7/20 resulted in 7 (+)/20 (-) for both the gastric cancer and the liver tumor. Therefore, we diagnosed the patient with gastric cancer, which occurred concomitantly with the metastatic liver tumor, and administered chemotherapy with S-1 plus cisplatin. After 3 courses of the regimen, a reduction in the size of mass was observed in the stomach and the liver. We subsequently performed left hepatectomy and total gastrectomy with lymph node dissection. Microscopic examination revealed the gastric cancer, which occurred simultaneously with the intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and the patient remains well without recurrences.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Cisplatin; Drug Combinations; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 40-year-old woman presenting with hilar cholangiocarcinoma and multiple liver metastases was admitted to our hospital. Initially, she underwent an extended right hepatectomy, 1 segmentectomy, and partial resection of the liver. After adjuvant chemotherapy with gemcitabine (1,000 mg/m² days 1, 8, and 15, of a 28-day cycle), multiple liver metastases (1 lesion in S2 and 2 lesions in S4) were detected by computed tomography (CT). As a result of the impaired response to gemcitabine, the chemotherapy regimen was changed to include combined chemotherapy with gemcitabine (1,000 mg/m² days 1 and 8, of a 21-day cycle), and S-1 (120 mg/body/day days 1 through 14). After 5 courses of combined chemotherapy, the liver metastases reduced in size; subsequently, a left internal sectionectomy and radiofrequency ablation were performed. Thereafter, the patient continued to receive adjuvant chemotherapy with S-1 for an additional 3 years; she is alive, without recurrence, 5 years after the initial operation. We propose that aggressive surgery should be considered for patients presenting with chemotherapy-responsive cholangiocarcinoma with multiple metastases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Catheter Ablation; Cholangiocarcinoma; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Hepatectomy; Humans; Oxonic Acid; Tegafur

A 72-year-old woman was diagnosed with liver dysfunction during a medical examination. An abdominal computed tomography (CT) scan showed multiple nodules in the left lobe, anterior segment, andposterior segment of the liver, leading to a diagnosis of intrahepatic cholangiocarcinoma (ICC). Extended left lobectomy and partial hepatectomy in the anterior and posterior segment with lymph node dissection was performed. At the time of the operation, small nodules on the peritoneum near the stomach were resected; these nodules were diagnosed as peritoneal disseminations of ICC. The histopathological diagnosis was moderately differentiated tubular adenocarcinoma (T4N0M1, Stage IVB). Adjuvant chemotherapy with S-1 was administered for 18 months. Thirty months after the operation, multiple lung metastases were detected by using CT, and chemotherapy with gemcitabine was initiated. Thirty-six months after chemotherapy with gemcitabine, the patient is alive and at home despite her lung metastases, which grew slightly in size. Herein, we report a long-term survival case of ICC with peritoneal dissemination that was successfully treated with surgical resection and adjuvant chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Chemotherapy, Adjuvant; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Hepatectomy; Humans; Lymph Node Excision; Oxonic Acid; Peritoneal Neoplasms; Tegafur

The patient was a 63-year-old male. He was admitted to our department due to obstructive jaundice and acute renal failure, and was diagnosed with a lower bile duct cancer. As a result of a stent placement into the bile duct and hemodialysis, jaundice and renal failure improved. As scattered metastases were recognized on the superior surface of both hepatic lobes in intraoperative findings, only a portoenterostomy was performed. After that, 1,000 mg/m(2) of gemcitabine(day 1)and 60 mg/m(2) day of S-1(days 1-7)were administered repeatedly every other week as a course. One year and four months after the start of chemotherapy, radiation therapy of 40 Gy was performed at the site considered to be the remaining primary tumor according to the PET-CT findings. While chemotherapy was continued without change thereafter, the time passed with no visualization of lesions by CT. Two years and five months after the start of chemotherapy, duodenal stenosis and a metastasis in the liver occurred, resulting thereafter in aggravated conditions and death. The entire course lasted two years and eight months. We considered that combined therapy of gemcitabine and S-1 would be a useful option in chemotherapy for biliary tract cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Fatal Outcome; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Tegafur

The significance of perineural invasion in extrahepatic cholangiocarcinoma has not been fully elucidated. This study aims to determine the prognostic impact of and optimal treatment strategy for perineural invasion in patients with extrahepatic cholangiocarcinoma.. Medical records of 133 patients with extrahepatic cholangiocarcinoma who underwent curative resection were reviewed retrospectively. Ninety-eight patients had perineural invasion and 35 patients did not. Univariate and multivariate survival analyses were performed to clarify the prognostic impact of and optimal treatment strategy for perineural invasion.. Only tumor differentiation (P=0.024) was independently associated with perineural invasion in the multivariate logistic regression model. Multivariate survival analysis revealed that perineural invasion (P=0.002), resection margin status(P=0.016), and International Union Against Cancer (UICC) pT factor (P=0.015) were independent prognostic factors of overall survival. Overall 5-year survival rates for patients with and without perineural invasion were 28 and 74 %, respectively. Among 98 patients with perineural invasion, the use of adjuvant chemotherapy (P=0.003), lymph node status (P=0.015), resection margin status (P=0.008), and UICC pT factor (P=0.016) were independently associated with overall survival by multivariate analysis. Overall 5-year survival rates for patients with perineural invasion who did and did not receive adjuvant chemotherapy were 33 and 21 %, respectively (P=0.023).. Perineural invasion is a potent prognostic factor in extrahepatic cholangiocarcinoma. Adjuvant chemotherapy may improve the overall survival of patients with perineural invasion.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Chemotherapy, Adjuvant; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Hepatectomy; Humans; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Neoplasm, Residual; Oxonic Acid; Peripheral Nerves; Proportional Hazards Models; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome

Simvastatin has inhibitory effects on cancers. The present study aimed to investigate the interactive effects between simvastatin and S-1 against bile duct cancer and its mechanisms. The effects of simvastatin and 5-fluorouracil (5-FU) alone or in combination on the growth and apoptosis of the human cholangiocarcinoma cell line EGI-1 and the gallbladder carcinoma cell line Mz-ChA-1 cells were evaluated in vitro. Real-time PCR and western blot were used to determine E2F-1 and thymidylate synthase (TS) expressions in the treated cells. Tumoricidal efficacy of simvastatin and S-1 was further investigated in a subcutaneous bile duct cancer model in NOD/SCID mice. Simvastatin enhanced the cytotoxicity of 5-FU on bile duct cancer cells in vitro. IC50 of 5-FU alone was 4.34 μmol/l for EGI-1 and 13.9 μmol/l for MZ-ChA-1, whereas it decreased markedly to 0.90 and 2.95 μmol/l, respectively, when combined with simvastatin. The Chou and Talalay combination index of 5-FU and simvastatin was 0.41 and 0.40 at IC50 for EGI-1 and MZ-ChA-1, respectively. Simvastatin alone or plus 5-FU significantly suppressed E2F-1 and TS expressions in EGI-1 and MZ-ChA-1. Simvastatin plus 5-FU induced greater proportion of apoptotic cells on both EGI-1 and MZ-ChA-1, with an increase in cleaved caspase-3 levels, compared with simvastatin or 5-FU alone (all P < 0.05). Simvastatin plus S-1 induced greater tumor inhibition than simvastatin or S-1 alone with E2F-1/TS downregulation in vivo (all P < 0.05). Simvastatin and S-1 exerted synergistic effects against bile duct cancer, which might be mediated by E2F-1/TS downregulation. The combination could be a reasonable regimen in the management of bile duct cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bile Duct Neoplasms; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Drug Combinations; Drug Screening Assays, Antitumor; Drug Synergism; E2F1 Transcription Factor; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Oxonic Acid; Simvastatin; Tegafur; Thymidylate Synthase; Xenograft Model Antitumor Assays

We report a case of bile duct cancer with a positive surgical margin obtaining long-term survival after S-1 monotherapy. A 79-year-old male with fever and liver dysfunction was admitted to our hospital. After a series of examinations he was diagnosed as hilar cholangiocarcinoma, which was treated with bile duct resection and biliary reconstruction for adhesion and pulmonary dysfunction of tuberculosis. Histopathological findings revealed that both surgical margins of the bile duct were positive. After operation, the patient received S-1 oral monotherapy(100mg/day for 28 days, followed by 14 days of rest)for 3 years. The patient has been alive for 5 years without recurrence.

Topics: Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Combined Modality Therapy; Drug Combinations; Humans; Male; Neoplasm Staging; Oxonic Acid; Tegafur; Time Factors; Tomography, X-Ray Computed

The aims of this study were to evaluate long-term outcomes and to determine prognostic factors for survival in patients with resected biliary carcinoma who received adjuvant gemcitabine plus S-1 chemotherapy.. Seventy patients with International Union Against Cancer (UICC) stage II, III, or IV biliary carcinoma received postoperative adjuvant chemotherapy consisting of intravenous gemcitabine 700 mg/m(2) on day 1 and oral S-1 60-100 mg/body for seven consecutive days, followed by a 1-week pause of chemotherapy. Patients received up to ten 2-week cycles. Long-term outcomes and predictors of survival with this adjuvant chemotherapy regimen were analyzed.. The median duration of follow-up was 47 months. Fifty-six percent of patients had node-positive disease, and 80% of patients underwent R0 resection. Overall and disease-free survival rates were 91 and 81% at 1 year, 56 and 55% at 3 years, and 40 and 46% at 5 years, respectively. Lymph node status (p = 0.025) and surgical margin status (p = 0.033) were independently associated with long-term survival by multivariate analysis.. Adjuvant gemcitabine plus S-1 chemotherapy may be a promising strategy for patients with resected biliary carcinoma, and nodal status and surgical margin status may be predictors of survival with this treatment strategy.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biliary Tract Neoplasms; Chemotherapy, Adjuvant; Cholangiocarcinoma; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Therapy, Combination; Female; Gemcitabine; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Oxonic Acid; Prognosis; Proportional Hazards Models; Tegafur

Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.

Topics: Aged; Aged, 80 and over; Aquaporin 1; Aquaporin 4; Aquaporin 5; Aquaporins; Bile Duct Neoplasms; Biomarkers, Tumor; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Prognosis; Tegafur

A 52-year-old male was presented with obstructive jaundice and liver dysfunction. He was diagnosed as hilar cholangiocarcinoma involving the confluence of the right and left hepatic duct and bifurcation of the main portal vein trunk. Swollen lymph nodes in the hepatoduodenal ligament were also detected. ERBD tubes were placed in each B2, 3, and 5 branch. GEM and S-1 combination chemotherapy was carried out for four months. As a reduction in the primary tumor and lymph nodes was observed on CT scan surgical exploration was conducted, and an extended left hepatectomy with partial resection of the portal vein and regional lymph node dissection was achieved. The postoperative course was uneventful, and the patient remained free of recurrence, 34 months after the original diagnosis was made, and 29 months after surgical resection. Thus, GEM and S-1 combination chemotherapy is one of the options for the management of advanced hilar cholangiocarcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Stents; Tegafur

Case 1:A 61-year-old man was diagnosed as cholangiocellular carcinoma with para-aortic lymph node metastasis (T4N1M0, cStage IV B). After 9 courses of chemotherapy using gemcitabine(GEM), CT scan showed that primary lesion and metastatic lymph nodes were reduced in size, and FDG-PET showed no FDG accumulation in the lymph nodes. The patient decided to continue additional chemotherapy with GEM and hyperthermia. Despite the chemo-hyperthermia, the primary tumor re-grew. He then underwent right trisegmentectomy, lymph node dissection, and reconstruction of the biliary tract. The final stage was T3N0M0, fStage III . Case 2: A 65-year-old man was diagnosed as cholangiocellular carcinoma with massive arterial invasion(T3N1M0, cStage IV B). After 3 courses of chemotherapy for GEM plus S-1, a CT scan revealed that the main tumor and metastatic lymph nodes were reduced in size, and he underwent extended left lobectomy of liver, lymph node dissection, and reconstruction of the biliary tract. The final stage was T1N0M0, fStage I . These cases indicated that neoadjuvant chemotherapy by gemcitabine was indeed promising for some cases of biliary tract cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography Scanners, X-Ray Computed

A 71-year-old man was referred to our hospital for further evaluation of hepatic dysfunction. A diagnostic workup revealed an intrahepatic bile duct cancer, and a right hepatic lobectomy was performed. Postoperative adjuvant chemotherapy with gemcitabine (1,000 mg/m², given for 3 weeks, followed by a 1 week rest) was begun. Because grade 3 anorexia developed, the dose of gemcitabine was decreased to 800 mg/m² from the third cycle of chemotherapy. Computed tomography showed nodal recurrence 6 months after surgery. One year after surgery, computed tomography revealed an extensive periaortic nodal recurrence, as well as recurrence in the remnant liver. Treatment was switched to S-1 (100 mg/ day, given for 3 weeks, followed by a 1 week rest). Grade 3 thrombocytopenia was developed during the tenth cycle of therapy. The treatment schedule was therefore changed to 3 weeks of therapy, followed by a 2 week rest. From the 36th cycle, the dose of S-1 was lowered to 80 mg/day (given for 2 weeks, followed by a 2 week rest). Nodal recurrence was resolved in 2 years after the start of treatment with S-1, and recurrence in the remnant liver nearly resolved in 4 years after starting the treatment, indicating a partial response. The carcinoembryonic antigen level fell to the normal range and the CA19-9 level remains at about 100 U/mL. Although the patient had grade 2 thrombocytopenia, he is now receiving the 43rd cycle of S-1 and remains alive for 5 years and 1 month after surgery. We believe that the continuation of chemotherapy while monitoring the patient's general condition led to an improved outcome.

Topics: Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Drug Combinations; Humans; Lymphatic Metastasis; Male; Oxonic Acid; Recurrence; Tegafur; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

A 60-year-old man with intrahepatic cholangiocarcinoma (ICC) underwent a left hepatectomy. Following the procedure, S-1 was administered during the period of five months. About two years after the hepatectomy, the patient underwent a hepatic resection again for remunant hepatic recurrences of ICC. Aggressive surgical resection may be the only method to assure a good outcome. An indication of resection for the hepatic recurrence of ICC will be examined in the future.

Topics: Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Gemcitabine; Hepatectomy; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed

A 60-year-old male patient was diagnosed as bile duct cancer with left neck and abdominal para-aortic lymph node metastasis. He was treated by combined chemotherapy of S-1 and gemcitabine(GEM). S-1 (120 mg/day) was administered 14 days followed by 14 days rest as one course. GEM (1,000 mg/m2) was administered at 8 and 15 days after the start of S-1. Combined therapy could be continued, though S-1 and GEM were reduced for neutropemia. After 5 courses of treatment, CT and MRCP revealed a partial response. S-1/GEM combined therapy was effective for inoperable biliary tract carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Deoxycytidine; Drug Combinations; Fatal Outcome; Gemcitabine; Humans; Lymphatic Metastasis; Male; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

To cure intrahepatic cholangiocarcinoma (ICC), only a surgical resection is the potential treatment at present. However, recurrence tumors in residual liver and/or distant organs even after curative surgery are commonly experienced in clinical course. Unfortunately the potential treatment for this recurrent disease is not established at present. Accordingly, the prognosis of this recurrent ICC is extremely poor. Here, we report the prolonged survival case with recurrent ICC after hepatic resection followed by combined therapy of intrahepatic arterial infusion with CDDP and S-1 administration. The patient was a 71-year-old female. She had been treated for hepatitis B for last 5 years. After that, liver tumor of 30 mm in diameter was detected in S1/8 by abdominal CT examination. Subsequently, caudate lobectomy and partial resection of Segment 8 were performed under the diagnosis of Hepatocellular carcinoma in Osaka university hospital. The pathological stage was T2N0M0, Stage II with moderately differentiated intrahepatic cholangiocarcinoma. As the recurrence tumor was found in Segment 4 of residual liver, we started a treatment with intrahepatic arterial infusion with CDDP and S-1 administration, immediately. These combined therapy displayed beneficial effects and a recurrent liver tumor was well controlled. At present, this patient is still survived for over 5 years after the operation.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Cisplatin; Drug Combinations; Female; Hepatic Artery; Humans; Infusions, Intra-Arterial; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

An 83-year-old man commuting to our hospital with postoperative ascending colon cancer was pointed out an increase of CA19-9. CT scan revealed an intrahepatic cholangiocarcinoma in the left lobe. In May 2007, an operation was performed. We recognized a lymph node swelling in the hepatoduodenal ligament. Pathologically, it was moderately differentiated adenocarcinoma. Therefore, the operation did only the cholecystectomy. Gemcitabine was administered once a week for 3 weeks followed by a week rest. It was administered for about 20 months and the evaluation during the period was PR or SD. Afterwards, the tumor had increased gradually. Gemcitabine was changed to S-1. Then, S-1 was changed to gemcitabine again because the enlargement of the tumor and the rise of tumor markers were observed. Consequently, tumor markers decreased. Now, the patient is under an outpatient care maintaining ADL.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Male; Oxonic Acid; Tegafur; Treatment Outcome

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin (CDDP). A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography (CT) showed low-density masses of 50 and 15 mm in diameter, respectively in segment VIII of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months after initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion. After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Drug Combinations; Drug Therapy; Female; Gemcitabine; Humans; Oxonic Acid; Tegafur; Treatment Outcome

Although chemotherapy for cholangiocellular carcinoma (CCC) is administered to those patients who are inoperable, the results are largely disappointing, especially for CCC producing parathyroid hormone-related peptide (PTHrP). We encountered a 43-year-old man with hypercalcemia due to PTHrP secretion of CCC. As the tumor was inoperable, we treated him with gemcitabine (GEM), S-1 and radiation. The tumor size was reduced 55% and the serum PTHrP level decreased markedly after the chemoradiotherapy. Although the patient died after 14 months, this case clearly suggests that the combined chemoradiotherapy of GEM, S-1 and radiation, may be useful for the treatment of CCC producing PTHrP.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Combined Modality Therapy; Drug Combinations; Humans; Male; Oxonic Acid; Parathyroid Hormone-Related Protein; Radiotherapy, Adjuvant; Tegafur

The patient was an 83-year-old man who had undergone pancreaduodenectomy for a diagnosed lower bile duct cancer in April 2004. CT demonstrated intra-abdominal lymph node enlargement 2 years postoperatively and CA19-9 increased. S-1, an oral fluoropyrimidine anticancer drug, was started as first-line chemotherapy. A complete response was confirmed after the first two courses of S-1 monotherapy. CR persisted for 2 years and S-1 was discontinued after 25th course because of long CR. No grade 3 or more toxicities were noted.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Drug Combinations; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pancreaticoduodenectomy; Tegafur

We report a case of successful multimodal treatment for combined hepatocellular and cholangiocarcinoma with portal venous tumor thrombus. A 66-year-old man was diagnosed with hepatocellular carcinoma with Vp3 by abdominal enhanced CT. He underwent a complete tumor resection and following interferon and 5-FU combined intra-arterial chemotherapy as an adjuvant setting. The histological findings were consistent with combined hepatocellular and cholangiocarcinoma. At 9 months after the surgery, lymph node metastases were detected. Then we started an oral fluoropyrimidine anticancer agent S-1, because the recurrence was suspected to be originated from the cholangiocarcinoma component. Thereafter, sustained partial remission was achieved. In case of combined hepatocellular and cholangiocarcinoma, we need to create a treatment strategy against characteristics of both components.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Combined Modality Therapy; Drug Combinations; Fluorouracil; Hepatectomy; Humans; Interferons; Liver Neoplasms; Male; Neoplastic Cells, Circulating; Oxonic Acid; Tegafur

A 65-year-old man with common bile duct cancer was treated by pylorus-preserving pancreaticoduodenectomy with D2 lymph node dissection. Three months after surgery, tumor marker was increasing, and CT demonstrated multiple liver metastatic tumors. Single drug chemotherapy with S-1(100 mg/body/day)was administered. After 6 months, the liver metastatic tumors could not be visualized by CT. S-1 may be the chemotherapy of choice for recurrence of bile duct cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Biomarkers, Tumor; Drug Combinations; Humans; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

Cholangiocarcinoma is a therapeutically challenging malignancy. This report describes a case where the patient received multimodal therapy, including surgery, adjuvant chemoradiation therapy, and combination chemotherapy and successfully achieved long-term survival. Specifically, the patient achieved an extended complete response after combination chemotherapy with TS-1 (an orally administered drug that is a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine [CDHP], and oteracil potassium [Oxo]) and cisplatin for recurrence. This result suggests that chemoradiation or combination chemotherapy regimens using oral 5-fluorouracil (5-FU) analogues might therefore be helpful in patients with this malignancy. However, further clinical trials are required.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Oxonic Acid; Tegafur

We experienced a case of good response in acute respiratory distress syndrome (ARDS) treated with sivelestat sodium hydrate during chemotherapy for cholangiocarcinoma. A 66-year-old male treated with combined paclitaxel (PTX) and S-1 suffered from ARDS following neutropenia. Sputum and blood culture examinations demonstrated an unknown origin, so sivelestat sodium hydrate was considered more effective than antibiotics. Sivelestat sodium hydrate ought to be used for ARDS treatment even during administration of anti-cancer agent.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Drug Administration Schedule; Drug Combinations; Glycine; Humans; Male; Neutropenia; Oxonic Acid; Paclitaxel; Respiratory Distress Syndrome; Serine Proteinase Inhibitors; Sulfonamides; Tegafur

Biliary tract cancers, including extrahepatic bile duct cancer, are often diagnosed at an advanced stage; however,no standard therapies have been established as yet for this disease,and new,effective chemotherapeutic agents are being sought. Recently, a late phase II study of S-1, an oral fluoropyrimidine, in 40 patients with advanced biliary tract cancer yielded a good response rate of 35.0%. In this article,we report two patients with advanced extrahepatic bile duct cancer enrolled in the study who showed a partial response to S-1 monotherapy.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Quality of Life; Tegafur

The patient was a 70-year-old man who in November 2000 had undergone pancreatoduodenectomy for a diagnosis of lower bile duct cancer by his previous physician. Left cervical and intra-abdominal lymph node enlargement were detected at 3 years 4 months postoperatively, and a biopsy resulted in a histopathological diagnosis of metastasis by bile duct cancer. Intravenous S-1,120 mg/body, on days 1-14, and CDDP, 20 mg/body, on day 14 was started in April 2004. It was conducted safely on an outpatient basis with no adverse events, and it was possible to achieve survival for 29 months. S-1/CDDP therapy seemed to be capable of serving as a useful treatment for gallbladder and bile duct cancer in the future.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cisplatin; Drug Combinations; Humans; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pancreaticoduodenectomy; Tegafur