The molecular mechanisms responsible for the progression of malignant transformation in Barrett's esophagus (BE) are still poorly understood. This study was undertaken (1) to investigate the gene and protein expression of cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor-gamma (PPARgamma), interleukin-8 (IL-8), hepatocyte growth factor (HGF), gastrin, and its receptor (CCK-2) in the Barrett's epithelium; (2) to analyze the activity of NFkappaB in Barrett's esophagus with low-grade dysplasia; and (3) to assess the effects of PPARgamma ligand (ciglitazone) and gastrin on cell proliferation in the cell line derived from esophageal adenocarcinoma (OE-33). COX-2, PPARgamma, IL-8, HGF, gastrin, and CCK-2 expression levels relative to the control gene encoding GAPDH were analyzed by RT-PCR and Western blot in specimens of BE with low-grade dysplasia (n = 20) and compared with that in the normal squamous esophageal mucosa from the middle portion of the esophagus (n = 20). In vitro experiments included the incubation of cell line OE-33 with ciglitazone (1-15 microM) and gastrin (100 nM). NFkappaB activity in biopsies specimens was measured by highly sensitive ELISA. COX-2, PPARgamma, IL-8, HGF, gastrin, and CCK-2 expressions were significantly increased in BE compared with normal squamous esophageal mucosa. NFkappaB activity was significantly upregulated in BE. Ciglitazone inhibited cell proliferation of OE-33 cells as assessed by BrdU and this effect was attenuated partly by gastrin. (1) COX-2, PPARgamma, HGF, gastrin, and its receptor are significantly upregulated in BE, suggesting a possible role for these factors in Barrett's carcinogenesis; (2) the increased NFkappaB activity is probably linked to increased IL-8 and COX-2 expression; and (3) PPARgamma ligands might be useful as a new therapeutic option in the prevention and treatment of Barrett's carcinoma.

In T2D with dementia, higher rates of hypoglycemia and other diabetes-related comorbidities were observed. Hence, the risks of a glucocentric and intense diabetes management with insulin and a focus on tight glycemic control without considering other factors may outweigh the benefits in elderly T2D patients with comorbid dementia.

Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.

Introduction-Laser lithotripsy of bile duct stones has become a widely accepted endoscopic treatment modality for giant, impacted, or very hard stones. The procedure is usually carried out under direct endoscopic control in view of the potential risk of bile duct injuries in "blind" laser application. Aims-To investigate the use of a rhodamine 6G laser lithotriptor with an integrated optical stone tissue detection system (oSTDS). Methods-From 1 September 1991 to 7March 1997, 60 patients with giant or impacted common bile duct stones refractory to endoscopic papillotomy stone extraction, and mechanical lithotripsy were treated via the endoscopic retrograde route using a rhodamine 6G dye laser (595 nm, 2.5 µs, 80-150 mJ pp, Lithognost Telemit/Baasel Corp., Germany) with integrated oSTDS. In case of tissue contact oSTDS cuts oV the laser pulse after 190 ns (transmission of 5-8% of the total pulse energy). 47 patients (78.3%) were subjected to x ray targeting (oSTDS) alone, five (8.3%) to choledochoscope targeting alone, and eight (13.3%) to both techniques. Results-At the end of treatment 52 (87%) patients were completely stone-free. The only major complications included transient haemobilia, cholangitis, and pancreatitis in five patients. All five were successfully treated by conservative methods. Conclusions-Laser lithotripsy using the described rhodamine 6G dye laser with oSTDS seems to be safe and eVective and allows "blind" fragmentation of diYcult common bile duct stones under radiological control only. (Gut 1998;43:823-829)

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