Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats.

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

Combined hepato-cholangiocarcinoma arising in a gallbladder intracystic papillary neoplasm. A new view on so-called "hepatoid adenocarcinoma of the gallbladder".

A 62-year-old female presented with abdominal pain, weight loss of 20 kg in the prior 6 months, and a palpable mass in the right upper quadrant during physical exam. Standard liver tests, including screening for hepatitis B and C and alpha-fetoprotein were negative or within normal limits. Computerized tomography depicted a transmural gallbladder tumor infiltrating into the adjacent liver with an irregular ill-defined mass occupying segments IV-V-VI, measuring 13.0 x 9.2 x 8.5 cm, with a solid-cystic component and heterogeneous captation of endovenous contrast media. Complete surgical resection of the neoplasm was achieved through an extended cholecystectomy and excision of hepatic segments IV, V and VI, with an uneventful follow-up 29 months until now. Morphological and immunohistochemical assessment favored a diagnosis of combined hepatocellular-cholangiocarcinoma arising in a gallbladder intracystic papillary neoplasm with invasive carcinoma. This case raises the hypothesis that the so-called "hepatoid adenocarcinoma of the gallbladder" may presently be better understood as a neoplasm derived from hepatobiliary stem/progenitor cells. Such cells have been recognized in the canals of Hering, in peribiliary glands within the liver and in the extrahepatic biliary tree, and in gallbladder mucosa.