The Efficacy and Safety of Steroids for Preventing Postembolization Syndrome after Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma.

Steroids are often administered at the time of transcatheter arterial chemoembolization (TACE), a standard treatment of hepatocellular carcinoma (HCC), with the expectation of preventing postembolization syndrome. Here we investigated the precise effects of steroids on TACE. We prospectively enrolled 144 HCC patients from 10 hospitals who underwent TACE. Three hospitals used steroids (steroid group, n=77) and the rest did not routinely use steroids (control group, n=67). The occurrence of adverse events and the algetic degree at 1-5 days post-treatment were compared between the groups. Fever (grades 0-2) after TACE was significantly less in the steroid group (56/21/0) compared to the control group (35/29/3, p=0.005, Cochran-Armitage test for trend). The suppressive effect of steroids against fever was prominent in females (p=0.001). Vomiting (G0/G1/ G2-) was also less frequent in the steroid group (70/5/2) versus the control group (53/10/3), but not significantly (p=0.106). The algetic degree and the grade of hematological adverse events, including hyperglycemia, did not differ between the groups. We conclude that the administration of steroids was useful for the prevention of adverse events after TACE in patients with HCC.

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development.

AIM: To investigate factors that accurately predict hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C (CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (AFP) to predict HCC development after interferon (IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/mL before therapy and in non-SVR patients showing AFP ≥ 5 ng/mL before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/mL before therapy and no decrease in AFP to < 5 ng/mL 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/mL before therapy and decreased AFP (P = 0.043). AFP ≥ 5 ng/mL before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/mL before therapy than in those showing AFP ≥ 5 ng/mL. CONCLUSION: The criteria of AFP < 5 ng/mL before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

Comparison of combined transcatheter arterial chemoembolization and radiofrequency ablation with surgical resection by using propensity score matching in patients with hepatocellular carcinoma within Milan criteria.

PURPOSE: To retrospectively compare the outcome of combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) with that of surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within the Milan criteria. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. From January 2000 to December 2010, 154 patients (mean age, 69.9 years; age range, 50-89 years; 107 men, 47 women) underwent TACE-RFA, and 176 patients (mean age, 66.9 years; age range, 29-83 years; 128 men, 48 women) underwent SR. Patients with HCC who underwent TACE-RFA or SR were enrolled if they met the following inclusion criteria: no previous HCC treatment, one HCC lesion no larger than 5 cm or up to three nodules smaller than 3 cm without vascular invasion or extrahepatic metastasis, and Child-Pugh class A or B disease. Cumulative overall survival (OS) and disease-free survival (DFS) rates were compared after adjustment with propensity score matching. RESULTS: After this adjustment, OS rates were comparable between the groups (P = .393), but DFS was superior in the SR group (P < .048). Among patients with very early stage HCC (lesions <2 cm in diameter), OS and DFS rates in the SR group were significantly higher than those in the TACE-RFA group (P < .001 and P = .008, respectively). However, adjustment with propensity score matching yielded comparable OS and DFS rates between the two groups (P = .348 and P = .614, respectively). CONCLUSION: TACE-RFA may be a viable alternative treatment for early-stage HCC when SR is not feasible.

Outcomes after curative treatment for cryptogenic cirrhosis-associated hepatocellular carcinoma satisfying the Milan criteria.

BACKGROUND AND AIM: The prognosis of cryptogenic cirrhosis-associated hepatocellular carcinoma (CC-HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC-HCC. METHODS: Consecutive 36 curatively treated CC-HCC patients satisfying the Milan Criteria were compared with corresponding 211 HCV-associated HCC (HCV-HCC) patients. The clinical background, tumor recurrence rate, overall survival rate, and prognostic values of the patients were assessed. RESULTS: The size of CC-HCCs was larger than that of HCV-HCCs (P = 0.01). The respective tumor recurrence rates at 1, 3, and 5 years were 11%, 32%, and 46% in the CC-HCC, and 21%, 59%, and 81% in the HCV-HCC. The respective overall survival rates at 1, 3, and 5 years were 94%, 85%, and 80% in the CC-HCC, and 98%, 81%, and 61% in the HCV-HCC. CC-HCC patients had a lower tumor recurrence rate and a higher survival rate compared to the HCV-HCC patients (P = 0.001 and P = 0.02, respectively). Via multivariate analysis, significant factors for high recurrence rate were number of HCCs (P = 0.02) and serum alpha fetoprotein levels (P = 0.03) in CC-HCC, whereas multiple tumors (P < 0.001), large tumor size (P = 0.01), and high alanine aminotransferase (P = 0.04) in HCV-HCC. The factor for survival was albumin in both groups. CONCLUSION: The size of CC-HCC was larger than that of HCV-HCC even in patients who received curative treatment; however, the risk for recurrence and the mortality of the patients with CC-HCC was lower than those with HCV-HCC.

Efficacy of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis.

PURPOSE: This study aimed to investigate the efficacy of ursodeoxycholic acid (UDCA) for Japanese patients with autoimmune hepatitis (AIH). METHODS: One hundred forty-seven patients were investigated. RESULTS: As initial treatment, 25 patients received UDCA (300-600 mg/day) monotherapy (UDCA group), 40 received a combination of prednisolone (PSL) (≥20 mg/day) and UDCA (combination group), 68 received PSL monotherapy (PSL group), and 14 received other treatments. During the follow-up, in the UDCA group, PSL was added to 8 of 12 patients failing to achieve the normalization of serum transaminase levels with UDCA monotherapy. Cumulative incidence of the normalization of serum transaminase levels was 64% in the UDCA group, 95% in the combination group, and 94% in the PSL group (log-rank test, P = 0.0001). UDCA group required longest periods until the normalization of serum transaminase levels. Eleven patients, who achieved persistent normalization of serum transaminase levels with UDCA monotherapy, did not reach liver failure or develop hepatocellular carcinoma for 49.7 (range = 13.4-137.3) months. Meanwhile, during the taper of PSL, doses of PSL at the initial relapse were lower in patients treated with PSL and UDCA than in those treated with PSL monotherapy, and initial relapse occurred earlier in patients treated with PSL monotherapy. CONCLUSIONS: UDCA monotherapy is effective for some Japanese AIH patients; however, UDCA monotherapy for patients with either high-grade inflammatory activity or poor residual capacity of liver function is not recommended because they may reach liver failure before achievement of remission. Meanwhile, additional use of UDCA during the taper of corticosteroids may be effective for the prevention of early relapse.

Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population.

PURPOSE: Recent routine testing for liver function and anti-mitochondrial antibodies has increased the number of newly diagnosed patients with primary biliary cirrhosis (PBC). This study investigated the prognosis of asymptomatic PBC patients, focusing on age difference, to clarify its effect on the prognosis of PBC patients. METHODS: The study was a systematic cohort analysis of 308 consecutive patients diagnosed with asymptomatic PBC. We compared prognosis between the elderly (55 years or older at the time of diagnosis) and the young patients (<55 years). The mortality rate of the patients was also compared with that of an age- and gender-matched general population. RESULTS: The elderly patients showed a higher aspartate aminotransferase-to-platelet ratio, and lower alanine aminotransferase level than the young patients (P < 0.01 and P = 0.03, respectively). The two groups showed similar values for alkaline phosphatase and immunoglobulin M. Death in the young patients was more likely to be due to liver failure (71%), while the elderly were likely to die from other causes before the occurrence of liver failure (88%; P < 0.01), especially from malignancies (35%). The mortality rate of the elderly patients was not different from that of the age- and gender-matched general population (standardized mortality ratio, 1.1; 95% confidence interval, 0.6-1.7), although this rate was significantly higher than that of the young patients (P = 0.044). CONCLUSIONS: PBC often presents as more advanced disease in elderly patients than in the young. However, the mortality rate of the elderly patients is not different from that of an age- and gender-matched general population.

Clinical features of type 1 autoimmune hepatitis in adolescence and early adulthood.

AIM: The peak age of the presentation of autoimmune hepatitis (AIH) is between 40 years and 50 years. Elderly patients have been reported to have higher frequencies of concurrent thyroid or rheumatic diseases and histological cirrhosis and a lower occurrence of treatment failure. In this study, we assessed the clinical features of Japanese type 1 AIH in adolescence and early adulthood. METHODS: Fifteen patients aged

Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis.

AIM: Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20-30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients. METHODS: A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique. RESULTS: Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (>/= 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups. CONCLUSIONS: ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful.

Endoscopic mucosal resection of primary anorectal malignant melanoma: a case report.

Anorectal melanoma is a rare malignant tumor with a poor prognosis. However, several studies have reported cases of long-term survival. In this report, we present a patient with anorectal melanoma who has survived for 9 years after endoscopic mucosal resection. An 85-year-old man was referred to our hospital for further examination and treatment of an anal tumor 2 cm in size. Endoscopic ultrasonography revealed that the depth of tumor invasion was confined to the submucosal layer. Endoscopic mucosal resection was performed, and the tumor was diagnosed as a malignant melanoma. The patient was followed without any additional treatment, which was per his wishes. Although melanoma recurred 4 times thereafter, endoscopic mucosal resection was performed for each recurrent lesion. Thus, he has been alive for 9 years since the first endoscopic mucosal resection without distant metastases. If the depth of tumor invasion is shallow, endoscopic mucosal resection is a useful option among other therapeutic modalities.

Human leukocyte antigen DR status and clinical features in Japanese patients with type 1 autoimmune hepatitis.

AIM: Human leukocyte antigen (HLA) DR status affects the clinical features of autoimmune hepatitis. In Caucasians, patients with DR3 have poorer outcomes. In Japan, the relationship between HLA DR status and clinical features has yet to be fully examined. METHODS: We investigated 79 patients with type 1 autoimmune hepatitis who underwent liver biopsy and were screened for HLA DR status by the polymerase chain reaction sequence specific oligonucleotide hybridization method. RESULTS: Fifty-five patients had DR4 and 23 had DR2. Thirteen patients had both DR2 and DR4. None had DR3. Of patients aged <30 years, 70% did not have DR4. A tendency toward higher serum levels of immunoglobulin G was seen in patients with DR4 compared to those without, while patients with neither DR2 nor DR4 had lower serum levels of immunoglobulin G than those with only DR2 and those with only DR4. Patients with DR2 had a lower frequency of concurrentautoimmune disease. Concurrence of thyroid disease was seen only in patients with DR4. The cumulative incidental rate of the normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was not associated with HLA DR status. CONCLUSION: HLA DR status is considered to affect the clinical features of Japanese patients with type 1 autoimmune hepatitis. Japanese patients with DR2 may have different clinical features from others. In addition, diagnoses of type 1 autoimmune hepatitis should be made carefully in Japanese patients with neither DR2 nor DR4 and in those aged <30 years.

Prognostic factors for fatal outcomes prior to receiving liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure.

BACKGROUND AND AIM: Many patients continue to die due to the rapid development of cerebral edema and/or multiple organ failure prior to receiving a liver transplantation. METHODS: We investigated the prognostic factors associated with 1-week fatal outcomes after the diagnosis of fulminant hepatic failure, which were associated with fatal outcomes prior to receiving liver transplantation, in 104 patients with non-acetaminophen-related fulminant hepatic failure. RESULTS: With a multivariate logistic regression analysis, age (>40 years), systemic inflammatory response syndrome (SIRS) and plasma prothrombin activities (40 years), cause of fulminant hepatic failure (viral hepatitis), plasma prothrombin activity (

Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis.

AIM: In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3-positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians. METHODS: We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16-79 years). RESULTS: Forty-seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%). CONCLUSION: In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre-existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without.

[A case of mixed duct-islet cell tumor of the pancreas].

A 30-year-old woman was referred to us because of hypoglycemic attack. The tumor on the pancreatic body of 22 mm size was revealed by close inspection, and was diagnosed as insulinoma. Surgical resection was performed, but curative resection was impossible because the component of adenocarcinoma infiltrating into surrounding tissue coexisted with insulinoma. Postoperatively, we make a diagnosis of combined tumor of the pancreas, i.e. mixed duct-islet cell carcinoma. In this paper, we discuss this rare disorder and summarize 33 cases reported in the Japanese literature.

Hepatic steatosis correlates with the postoperative recurrence of hepatitis C virus-associated hepatocellular carcinoma.

BACKGROUND: Hepatic steatosis is a prominent feature of chronic hepatitis C. Hepatic steatosis was reported recently to be a risk factor for hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). AIM: To investigate whether hepatic steatosis influences the postoperative recurrence of HCV-associated HCC. METHODS: A retrospective study was conducted in 88 patients undergoing curative resection of HCV-associated HCC. Cumulative tumour recurrence rates were compared between steatosis-positive and steatosis-negative patients, and the factors affecting intrahepatic recurrence were assessed. RESULTS: The respective tumour recurrence rates at 1, 3, and 5 years were 19%, 76%, and 92% in the steatosis-positive group, and 12%, 52%, and 60% in the steatosis-negative group. The tumour recurrence rate of the steatosis-positive group was significantly higher than that of the steatosis-negative group (P=0.02). Hepatic steatosis [relative risk (RR)=3.31, 95% confidence intervals (CIs)=1.49-7.41, P=0.003], stage of fibrosis (RR=3.17, 95% CI=1.35-7.47, P=0.008), surgical procedure (RR=0.22, 95% CI=0.076-0.64, P=0.005), number of tumours (RR=5.24, 95% CI=1.63-16.80, P=0.005), size of the largest tumour (RR=3.52, 95% CI=1.28-9.69, P=0.02), and vascular invasion (RR=2.72, 95% CI=1.32-5.59, P=0.007) were independent factors for tumour recurrence rate by multivariate analysis. CONCLUSIONS: Hepatic steatosis is a useful predictor of postoperative recurrence of HCV-related HCC.

Gastric ulcer after prophylactic balloon-occluded retrograde transvenous obliteration.

A 74-year-old man with compensated hepatitis C virus-related liver cirrhosis was admitted for the treatment of small hepatocellular carcinoma (HCC) by radiofrequency ablation therapy (RFA). As a routine pretreatment examination, gastrointestinal endoscopy was performed, and large nodular varices were observed in the gastric fornix, with telangiectasia on top of the varices. As soon as the RFA was completed, prophylactic balloon-occluded retrograde transvenous obliteration (B-RTO) was performed. Seven days after the B-RTO, the patient complicated of upper abdominal pain. Gastrointestinal endoscopy was performed, and a deep ulcer, located at the top of the tumor-shaped gastric varices, was found. The ulcer showed rapid healing after 1-week administration of a proton pump inhibitor (PPI). A severe ulcer after a B-RTO procedure, is extremely rare, because sclerosing agents rarely flow into the gastric mucosa. The ulcer in this patient was deep and large, and it may have been due to direct mucosal damage caused by the sclerosing agent, because mucosal telangiectasia on top of the varices was observed before the B-RTO. It is likely that, in this patient, the mucosal vessels communicated with the submucosal large varices, and ethanolamine oleate (EOI) flowed into the gastric mucosa via this communication. Based on our experience, we recommend periodic follow-up endoscopy.

Simple surrogate index of the fibrosis stage in chronic hepatitis C patients using platelet count and serum albumin level.

This study was conducted to develop a simple surrogate index comprised of routinely available laboratory tests to reflect the histological fibrosis stage. Clinical characteristics and laboratory data from 368 and 249 consecutive patients with chronic hepatitis C, a training cohort and a validation cohort, respectively, were retrospectively evaluated. Platelet (Plt) count and albumin (Alb) level contributed to the discrimination of the respective fibrosis stages. We derived the fibrosis index (FI), FI = 8.0-0.01 x Plt (10(3)/microliter) - Alb (g/dl), from a multiple regression model. FI significantly correlated with the histological fibrosis stage in both the initial and validation cohort at rho=0.691 and rho=0.661, respectively (Spearman's rank correlation coefficient, p<0.0001). The sensitivity and positive predictive value of FI at a cutoff value < 2.10 for predicting fibrosis stage F0-1 were 66.8% and 78.8% in the initial cohort and 68.5% and 63.6% in the validation cohort, respectively. Corresponding values of FI at a cutoff value > or = 3.30 for the prediction of F4 were 67.7% and 75.0% in the initial cohort and 70.8% and 81.0% in the validation cohort. The fibrosis index comprised of platelet count and albumin level reflected the histological fibrosis stage in patients with chronic hepatitis C.

Prophylactic balloon-occluded retrograde transvenous obliteration for gastric varices in compensated cirrhosis.

BACKGROUND & AIMS: Because gastric variceal bleeding is associated with a high mortality rate, its prophylaxis is expected to improve survival. We investigated the effectiveness of balloon-occluded retrograde transvenous obliteration (B-RTO) for the treatment of gastric fundal varices. METHODS: A prospective nonrandomized study was conducted. Prophylactic B-RTO was performed in 17 patients (B-RTO group), whereas the remaining 17 patients received no specific treatment (control). The nonbleeding rate, cumulative survival rate, and prognostic values of the patients were assessed. RESULTS: The respective nonbleeding rates at 1, 3, and 5 years were 100%, 100%, and 83% in the B-RTO group and 81%, 59%, and 39% in the control. The respective cumulative survival rates at 1, 3, and 5 years were 94%, 85%, and 39% in the B-RTO group and 71%, 41%, and 22% in the control. Both the nonbleeding rate and the cumulative survival rate of the B-RTO group were significantly higher than those of the control (P = .01 and .04, respectively). B-RTO was determined by multivariate analysis to be a significant factor for low bleeding rate (relative risk, 0.06; 95% confidence interval [CI], 0.004-0.79), whereas B-RTO (0.11; 95% CI, 0.03-0.44) and Child-Pugh class A (0.10; 95% CI, 0.03-0.39) were the significant factors for a low mortality rate, and the presence of hepatocellular carcinoma (5.68; 95% CI, 1.49-21.7) was the significant factor for a high mortality rate. CONCLUSIONS: Prophylactic B-RTO is effective in preventing gastric variceal rupture and consequently improves patient survival.

New prognostic scoring model for liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure.

BACKGROUND: Many patients with fulminant hepatic failure die before receiving liver transplantation because of the difficulty of pinpointing the suitable timing for liver transplantation. The revised King's College criteria are useful for patients with acetaminophen-related fulminant hepatic failure; however, in those with non-acetaminophen-related fulminant hepatic failure, a new prognostic system that can accurately identify the suitable timing for liver transplantation is required. METHODS: Using the first sample consisted of eighty patients with fulminant hepatic failure, we examined 2-week poor prognostic parameters at the time of diagnosis of fulminant hepatic failure (day 1) and on days 4, 8, and 15, respectively, and a 2-week prognostic scoring model was constructed. To confirm the accuracy of this model, validation was performed in the second sample consisting of 26 patients. RESULTS: Cause of fulminant hepatic failure (hepatitis B virus or indeterminate), hepatic coma grade (III or IV), systemic inflammatory response syndrome (yes) and ratio of total to direct bilirubin (> 2.0) were associated with 2-week outcomes during days 1-15. Each of these four parameters was valued at +1. The 2-week survival rate in patients scoring <3 was > or = 80% in contrast to less than 30% in patients scoring > or = 3. When this scoring model was applied to the second sample, the sensitivity, specificity, and positive and negative predictive values were 87.5%, 90.0%, 93.3%, and 81.8%, respectively. CONCLUSIONS: This scoring model may be useful for predicting 2-week outcomes and determining the suitable timing for liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure.

[Locally advanced pancreatic cancer that enlarged after administration of gemcitabine and responded to oral TS-1--a case report].

We administered oral TS-1 alone for locally advanced pancreatic cancer that did not respond to gemcitabine (GEM). A 56-year-old man was admitted to our hospital because of obstructive jaundice due to stage III pancreatic head cancer. We performed chemotherapy using GEM at a dose of 1,000 mg/m(2) after reduction of jaundice by PTCD and stenting. Once the tumor was reduced, enlargement was confirmed after 8 months, and cholangitis appeared due to stent obstruction. After PTCD and stenting (stent in stent) were performed again,we administered oral TS-1 alone at a dose of 100 mg/body. We achieved antitumor activity again using TS-1. It is suggested that TS-1 is a useful second-line agent for pancreatic cancer.