Cholangiocarcinoma (CCA) is a lethal disease, afflicting many thousands the world over. Human CCA develops through a multi-step progression model, preceded by the onset of dysplasia in the cholangiolar ductal epithelium. An animal model of multi-step carcinogenesis in the biliary tree will enable the study of genetic changes in human CCA, and provide an avenue for chemoprevention strategies. We describe an oral thioacetamide (TAA)-induced model of rat CCA that recapitulates the histologic progression of human CCA. Male Sprague–Dawley (SD) rats ( n = 170), weighing 350 ± 20 g, were used in this study. Drinking water with TAA 300 mg/l was administered orally, and the liver was harvested and examined histologically at weekly intervals, beginning at 5 weeks after initiation of TAA. Harvested tissues were formalin-fixed and paraffin embedded for morphologic and immunohistochemical studies. Multifocal bile ductular proliferation with intestinal metaplasia (presence of goblet cells) and increasing histologic atypia (biliary dysplasia) was observed by the 9th week of TAA administration. Biliary cytokeratin (CK19)-expressing invasive intestinal-type CCA with stromal desmoplasia was evident at the 16th week, and by the 22nd week, the yield rate for CCAs had increased to 100%. Invasive CCAs preceded the development of hepatic cirrhosis by at least 4 weeks; the earliest incidence of hepatic fibrosis was observed beginning at 20 weeks post-TAA administration. The progression from normal cholangioles to biliary dysplasia to invasive CCA was accompanied by up-regulation of the proto-oncogenes c-met and c-erbB-2, tyrosine kinase receptors over-expressed in human CCAs. The study was terminated at 6 months, at which time no systemic metastases or deaths were observed. Oral administration of TAA in drinking water to male SD rats provides a reproducible animal model for development of CCA with a high yield rate. In particular, the presence of biliary dysplasia beginning at the 9th week, which progresses to invasive CCA, mimics the multi-step model of human CCA. The TAA rat model may serve as a powerful pre-clinical platform for therapeutic and chemoprevention strategies for human CCA.

Gastrointestinal stromal tumors (GISTs) originating from the interstitial cells of Cajal are mesenchymal tumors of the gastrointestinal tract and have been found to harbor c-KIT mutations and KIT (CD117) expression since 1998. Later, PDGFRA mutations, SDH alterations, and other drive mutations were identified in GISTs. In addition, more and more protein markers such as DOG1, PKCθ were found to be expressed in GISTs which might help clinicians diagnose CD117-negative GISTs. Therefore, we plan to comprehensively review the molecular markers and genetics of GISTs and provide clinicians useful information in diagnostic and therapeutic strategies of GISTs. Twenty years after the discovery of KIT in GISTs, the diagnosis of GISTs became much more accurate by using immunohistochemical (IHC) panel (CD117/DOG1) and molecular analysis (KIT/PDGFRA), both of which constitute the gold standard of diagnosis in GISTs. The accurately molecular diagnosis of GISTs guides clinicians to precision medicine and provides optimal treatment for the patients with GISTs. Successful treatment in GISTs prolongs the survival of GIST patients and causes GISTs to become a chronic disease. In the future, the development of effective treatment for GISTs resistant to imatinib/sunitinib/regorafenib and KIT/PDGFRA-WT GISTs will be the challenge for GISTs.

To determine the timing of mortality after onset of severe acute pancreatitis (SAP) and the course of the disease in a large series of patients. From July 1996 to June 2005, all patients diagnosed with acute pancreatitis at Chang Gung Memorial Hospital, Taipei, Taiwan were retrospectively studied. Three thousand two hundred and fifty episodes of acute pancreatitis were recorded in 2248 patients (1431 males and 817 females; median age, 55.6 years; range, 18-97 years). Mortality was divided into two groups: early death (<= 14 d after admission), and late death (> 14 d after admission). The clinical features of patients in these two groups were compared. Although the overall mortality rate of acute pancreatitis was 3.8% (123/3250), mortality rate of SAP was as high as 16.3% (105/643). Of those 105 SAP mortalities, 44 (41.9%) deaths occurred within the first 14 d after admission and 61 (58.1%) occurred after14 d. Incidence of early death did not significantly differ from that of late death. The co-morbidities did not contribute to the timing of death. Early deaths mainly resulted from multiple organ failure. Late deaths were mainly caused by secondary complication of infected necrosis. Intra-abdominal bleeding significantly caused higher mortality in late death. Approximately half (42%) of SAP deaths occur within 14 d and most were due to multiple organ failure. The late deaths of SAP were mostly due to infected necrosis.