Prognostic significance of PUMA in pancreatic ductal adenocarcinoma.

OBJECTIVES: To investigate retrospectively whether alterations of p53 upregulated mediator of apoptosis (PUMA) protein levels and somatic mutations of the PUMA gene are characteristic of pancreatic ductal adenocarcinoma (PDAC). METHODS: Immunohistochemical analyses of PUMA were performed in pancreatic tumour tissue samples, and paired normal pancreatic tissue samples, from patients with PDAC. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assay. RESULTS: A total of 70 patients with PDAC had samples available; 49 cases (70.0%) had high PUMA protein levels. PUMA was not detected in paired normal tissue samples. Significantly higher levels of PUMA protein were detected in low-grade tumours (tumour -node-metastasis stages I and II), compared with higher grade (stage III) tumours. Of the PDAC cases, the mean apoptosis index value for PUMA-positive specimens was significantly higher than that for PUMA-negative specimens. Overall survival was significantly associated with PUMA immunoreactivity. CONCLUSIONS: High levels of PUMA in PDAC tumour cells suggest that PUMA expression may play a role in pancreatic tumourigenesis.

Primary eosinophilic disorders of the gastrointestinal tract.

Eosinophils are important effector cells of the innate immune system. Eosinophilic infiltrative disorders of the gastrointestinal tract, though recognised for decades, have recently witnessed a resurgence of interest, particularly for oesophageal disease. A more comprehensive basis for eosinophilic infiltration and activation has identified interleukin 5 (IL5) as a key cytokine for the differentiation and proliferation of eosinophils, while eotaxins promote the recruitment of mature eosinophils to the gut. When activated, eosinophils release multiple cytotoxic agents and immunomodulatory cytokines, resulting in local inflammation and tissue damage. Although eosinophils normally convey a defence against unwanted interlopers such as parasites, in the absence of such inciting agents, their accumulation and activation can elicit the primary infiltrative disorders of the gut: eosinophilic oesophagitis, gastroenteritis and colitis. Diagnosis of these disorders is dependent on the clinical presentation, endoscopic findings (particularly for eosinophilic oesophagitis), and most importantly, histological confirmation. Dietary modifications and topical corticosteroids are first-line treatments for eosinophilic oesophagitis. Systemic corticosteroids are the mainstay of treatment for eosinophilic gastroenteritis; surgery may be required depending on the layer of mucosa involved. Eosinophilic colitis most often occurs in infants; removal of the causative allergen usually results in a complete response. Steroids may be required for older children/adolescents or adults. This review summarises current knowledge on the trafficking of eosinophils to the gastrointestinal tract and the clinical management of the primary disorders of eosinophilic oesophagitis, eosinophilic gastroenteritis and eosinophilic colitis.

In vivo real-time endocytoscopic visualization of blood flow in rectal microvasculature.

Endocytoscopy (ECS) is a new technology that enables endoscopists to visualize gastrointestinal mucosa at the cellular level. This reported case demonstrates the ability to visualize real-time blood flow utilizing ECS. Methylene blue dye was sprayed onto normal rectal mucosa during a routine screening colonoscopy of an asymptomatic patient. High-magnification views of colonic mucosa revealed normal mucosal cellular structure and microvasculature with normal flow of red blood cells. Individual red blood cells were seen circulating through the arterioles. Epithelial colonocytes appeared to be organized in a hexagonal pattern around crypts with borders demarcated by microvasculature. ECS can provide high-magnification views of the gastrointestinal mucosa including microvasculature in real time. This establishes possibilities for future in vivo research in areas such as cancer biology, angiogenesis, and inflammatory bowel disease.