Efficacy of chemotherapy in elderly patients with unresectable pancreatic cancer: a multicenter review of 895 patients.

BACKGROUND: The efficacy of chemotherapy for unresectable pancreatic cancer has improved. However, it is occasionally difficult to make treatment decisions for elderly patients. We reviewed the outcomes of elderly patients with unresectable pancreatic cancer by using a large cohort and evaluated whether they had received chemotherapy and the reason why. METHODS: Data for 895 pancreatic cancer patients who were treated using chemotherapy or best supportive care were analyzed considering demographics, clinical stage, treatment, and outcome. Data were analyzed using the chi-square test, Student t-test, or Mann-Whitney U-test, as appropriate. Outcomes were analyzed using the Kaplan-Meier method. Differences in survival were analyzed using the log-rank test. RESULTS: The median survival time was significantly shorter in elderly patients (≥65 years) than in younger patients (<65 years) (181 vs. 263 days, P = 0.0001). The median survival time of patients treated with chemotherapy was not significantly different between the elderly and the younger group (274 days vs. 333 days, P = 0.09), and nor was that of patients choosing best supportive care (84 days vs. 78 days, P = 0.83). These results held true even when the age cut-off between younger and elder patients was increased to 70, 75, and 80 years. Elderly patients treated with chemotherapy had a significantly longer median survival time than those choosing best supportive care (274 vs. 86 days, P < 0.0001); a significantly greater proportion of elderly patients chose best supportive care compared to younger patients (47.8 vs. 25.8%, P < 0.0001). The reason for choosing best supportive care was established in 261 elderly patients (82.9%); 133 (51.0%) met the eligibility criteria for chemotherapy, but of these, 78 (58.6%) were not informed about their disease. The treatment preferences of elderly patients were not always considered; they often received only best supportive care per family members preference (N = 65, 48.8%) or because the physician based their treatment decision only on the patient's age (N = 68, 51.1%). CONCLUSIONS: Chemotherapy appears effective for elderly pancreatic cancer patients with unresectable disease, but treatment needs to be optimized to improve prognosis.

Improvement of long-term outcomes in pancreatic cancer and its associated factors within the gemcitabine era: a collaborative retrospective multicenter clinical review of 1,082 patients.

BACKGROUND: Although the outcomes of pancreatic cancer have been improved by gemcitabine, the changes in its characteristics and long-term outcomes within the gemcitabine era remain unclear. This study was conducted to identify clinical characteristics of pancreatic cancer patients within the gemcitabine era. METHODS: A retrospective chart review was performed at 10 centers for 1,248 consecutive patients who were ever considered to have a diagnosis of pancreatic cancer between 2001 and 2010. Data collected included demographics, diagnosis date, clinical stage, treatment, and outcome 1,082 patients met the inclusion criteria and were analyzed further. The chi-square test, Student's t-test, and Mann-Whitney U-test were used for statistical analysis. Outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Differences in survival analyses were determined using the log-rank test. RESULTS: The distribution of clinical stages was: I, 2.2% II, 3.4% III, 13% IVa, 27% and IVb, 55%. Chemotherapy alone was administered to 42% of patients and 17% underwent resection. The 1-, 3-, and 5-year survival rates were 39%, 13%, and 6.9%, respectively. The median survival time was 257 days, but differed considerably among treatments and clinical stages. Demographics, distribution of clinical stage, and cause of death did not differ between groups A (2001-2005, n=406) and B (2006-2010, n=676). However, group B included more patients who underwent chemotherapy (P<0.0001) and fewer treated with best supportive care (P=0.0004), mirroring improvements in this group's long-term outcomes (P=0.0063). Finally, factors associated with long-term outcomes derived from multivariate analysis were clinical stage (P<0.0001), location of the tumor (P=0.0294) and treatments (surgery, chemotherapy) (<0.0001). CONCLUSIONS: Long-term outcomes in pancreatic cancer has improved even within the gemcitabine era, suggesting the importance of offering chemotherapy to patients previously only considered for best supportive care. Most patients are still diagnosed at an advanced stage, making clinical strategy development for diagnosing pancreatic cancer at earlier stages essential.

Comparison of outcomes between patients with alcoholic cirrhosis and those with hepatitis C virus-related cirrhosis.

BACKGROUND AND AIM: The natural history of alcoholic cirrhosis, especially in Asian countries, has not been completely understood thus far. METHODS: We retrospectively compared the outcomes of compensated cirrhosis between Japanese alcoholic and hepatitis C virus (HCV)-infected patients. RESULTS: A total of 227 patients (75 alcoholic and 152 HCV-infected patients) with compensated cirrhosis were enrolled. The median follow-up period was 4.9 years. The cumulative rates of hepatocellular carcinoma (HCC) development were significantly lower in the alcoholic patients than in the HCV-infected patients (6.8% vs 50.3% at 10 years, P = 0.0003), while the cumulative rates of hepatic decompensation (37.4% vs 51.7% at 10 years) and survival (53.8% vs 47.4% at 10 years) did not significantly differ between the two groups (Kaplan-Meir analysis). The main causes of death were hepatic failure and non-hepatic diseases in the alcoholic patients and HCC and hepatic failure in the HCV-infected patients. Multivariate analyses using the Cox proportional hazard model revealed that the risk of HCC was lower in alcoholic cirrhosis than in HCV-related cirrhosis (hazard ratio (HR), 0.46), while the risk of hepatic decompensation and mortality was the same. Predictors of decreased survival were non-abstinence (HR, 2.53) in the alcoholic patients and low serum albumin level (1.58) in the HCV-infected patients. CONCLUSIONS: Survival of patients with alcoholic cirrhosis was similar to that of patients with HCV-related cirrhosis. The risk of HCC development was lower in alcoholic cirrhosis than in HCV-related cirrhosis. Abstinence from alcohol was important for improving the survival of patients with alcoholic cirrhosis.

Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura.

Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year-old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 x 10(9)/L to 8 x 10(9)/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB1*0601 and DRB1*0803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP.

Early pancreatic volume reduction on CT predicts relapse in patients with type 1 autoimmune pancreatitis treated with steroids.

BACKGROUND: Type 1 autoimmune pancreatitis (AIP) is clinically characterized by a response to steroid therapy. Despite having a favorable prognosis, AIP has a high relapse rate and factors predicting relapse in AIP patients treated with steroids have not yet been established. METHODS: A retrospective chart review was conducted of 32 newly diagnosed type 1 AIP patients who had undergone enhanced computed tomography (CT) pre- and post-steroid therapy. RESULTS: Ten patients experienced relapse. Pancreatic volume was reduced significantly in all patients (pre-treatment volume, 88.5 ± 32.9 cm(3) vs. post-treatment volume, 45.4 ± 21.1 cm(3); P < 0.001), although the pre-treatment pancreatic volume did not differ between the relapse and non-relapse groups (92.6 ± 10.5 cm(3) vs. 86.6 ± 7.1 cm(3), P = 0.401). However, the post-treatment pancreatic volume was significantly greater in the relapse group than that in the non-relapse group (56.9 ± 6.3 cm(3) vs. 40.2 ± 4.2 cm(3), P = 0.008). Similarly, the percent reduction in pancreatic volume was significantly smaller in the relapse group than that in the non-relapse group (36.6 ± 4.7 % vs. 52.1 ± 3.2 %, P = 0.002). Multivariate analysis identified post-treatment pancreatic volume (HR, 1.04, 95 % CI: 1.01-1.08, P = 0.010) and percent reduction in pancreatic volume (HR, 0.87, 95 % CI: 0.79-0.94, P < 0.001) as predictive factors for relapse of type 1 AIP. A post-treatment pancreatic volume of 50 cm(3) < (P = 0.009) and a percent reduction in the pancreatic volume of <35 % (P = 0.004) had a significantly high relapse rate. These data suggest that early pancreatic volume changes after steroid therapy may be a useful prognostic value, because type 1 AIP patients with a high post-treatment pancreatic volume or low pancreatic volume reduction showed significant relapse. CONCLUSIONS: Early pancreatic volume reduction on CT after steroid therapy indicates the therapeutic effects of steroids, and a low decrease in the pancreatic volume may be associated with a limited response that predicts future relapse in patients with type 1 AIP. Reduction of steroids in these cases must be observed carefully with consideration of immunomodulator use.

Wilson's disease masquerading as nonalcoholic steatohepatitis.

BACKGROUND: Wilson's disease is one of the most common hereditary causes of unclear hepatopathy. PATIENT #ENTITYSTARTX00026; METHOD: A 34-year old male patient with a history of hyperlipidemia was admitted with symptoms of abdominal pain and slight hematuria. Abnormal liver function tests, ultrasound reports and liver biopsy were suggestive of nonalcoholic steatohepatitis (NASH). The patient received preliminary treatment for NASH. However, on subsequent follow-up, NASH remained unresolved and liver histology showed fibrosis progression from fibrosis stage 1 to stage 3. RESULTS: Biochemical tests revealed that the levels of serum ceruloplasmin were decreased (7mg/dl) while the urinary excretion of copper was found to be increased (174.2 µg/day). Wilson's disease was confirmed by diagnostic mutation analysis involving Direct Sequencing. Heterogeneity in the patient's ATP7B gene confirmed Wilson's disease. Administration of D-penicillamine resulted in a decrease in fat deposition in the liver and no further progression in fibrosis after 10 months. CONCLUSION: Adult patient presenting NASH as first symptoms need to be examined for Wilson's disease and other metabolic conditions affecting the liver, prior to initiation of treatment.