Monotherapy with S-1 demonstrated noninferiority to gemcitabine in overall survival with good tolerability and presents a convenient oral alternative for locally advanced and metastatic pancreatic cancer.

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Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia.

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Background:The long term outcome of endoscopic papillotomy (EPT) is not well known. The aims of this study were to clarify the clinical course of post-EPT patients and to detect predictors for bile duct stone recurrence. Methods: A total of 1042 consecutive patients who underwent EPT for bile duct stones from December 1975 to September 1998 were prospectively followed up. Patients were divided into four groups according to gall bladder (GB) status: "acalculous GB" group, "calculous GB" group, "cholecystectomy" group, and "prior cholecystectomy" group. Reliable follow up information was obtained for 983 (94.3%) of the 1042 patients. The following factors were considered in the evaluation of predisposing risk factors for recurrence of bile duct stones: age, sex, gall bladder status, periampullary diverticulum, number of bile duct stones, diameter of bile duct stones, diameter of bile duct, lithotripsy, precutting, pneumobilia, and early complications. Results: Recurrence occurred in 111 patients. The "acalculous GB" group was less prone to recurrence than the "prior cholecystectomy" group and the "calculous GB" group. The relative risks (RR) for the latter two compared with the former group were 2.26 (95% confidence interval (CI) 1.24-4.14; p=0.0078) and 2.16 (95% CI 1.21-3.87; p=0.0093), respectively. Other prognostic factors were lithotripsy (RR 2.37; 95% CI 1.47-3.81; p=0.0004) and pneumobilia (RR 1.57; 95% CI 1.01-2.43; p=0.044). Conclusions: Gall bladder status, lithotripsy, and pneumobilia were significantly related to bile duct stone recurrence after EPT.