Upper gastrointestinal complications associated with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer.

BACKGROUND: Little is known about acute upper gastrointestinal (GI) complications associated with gemcitabine-concurrent proton radiotherapy (GPT) for inoperable pancreatic cancer. We investigated acute GI complications following GPT in patients with inoperable pancreatic cancer using small-bowel endoscopy. METHODS: This prospective single center observational study was conducted at the Hyogo Ion Beam Medical Center from January 2010 to January 2012. Ninety-one patients who had clinically and medically inoperable pancreatic cancer treated by GPT were analyzed. Endoscopic examinations were performed before and after GPT to clarify the incidence rates of radiation-induced ulcers, GI hemorrhage, and GI perforation associated with GPT. RESULTS: Post-treatment endoscopic examinations revealed that 45 (49.4 %) patients had radiation-induced ulcers in the stomach and duodenum. Of those, many ulcerative lesions were found in the lower stomach (51 %) and horizontal part of the duodenum (39 %), regardless of the primary tumor site in the pancreas. Neither GI hemorrhage, nor perforation, was found in post-treatment endoscopy examinations. CONCLUSION: Approximately half of the patients treated with GPT for inoperable pancreatic cancer exhibited radiation-induced ulcers in the stomach and duodenum.

Therapeutic effects of mosapride citrate and lansoprazole for prevention of aspiration pneumonia in patients receiving gastrostomy feeding.

BACKGROUND: Aspiration pneumonia is an emerging problem in patients receiving gastrostomy feeding. This study is designed to clarify the therapeutic effects of mosapride citrate and lansoprazole for prevention of aspiration pneumonia in patients receiving gastrostomy feeding. METHODS: The study subjects were 119 patients with dysphasia who required gastrostomy feeding. They were randomly assigned to the control (without medication), lansoprazole (15 mg, 1/day), and mosapride (5 mg, 3/day) groups. The number of days with fever (≥37.8 °C), vomiting, and antibiotics administration, as well as the occurrence of pneumonia were investigated during the 6-month observation period. RESULTS: The incidence of pneumonia during the observation period was significantly lower in the mosapride group as compared to the control (7/38 vs. 16/40, p = 0.038) and lansoprazole (vs. 20/41, p = 0.005) groups. The mosapride group also showed a significant decrease in days with fever and antibiotics administration as compared to the other groups. Multivariate analysis revealed that the presence of hiatal hernia was a significant risk factor and administration of mosapride was a significant preventive factor for pneumonia. CONCLUSION: Mosapride has a preventive effect on occurrence of pneumonia in patients receiving gastrostomy feeding.

Superficially elevated-type serrated hyperplastic lesion of the stomach with minute adenocarcinoma.

We report a case of gastric serrated hyperplastic lesion with minute adenocarcinoma. A 65-year-old Japanese man underwent endoscopic submucosal dissection to the superficially elevated-type (0-IIa) lesion located at the lesser curvature of the gastric angle. Histological observation revealed hyperplastic change of foveolar epithelium with serrated glandular structure as well as a minute tubular adenocarcinoma component. Immunohistochemically, the lesion demonstrated gastrointestinal, predominantly gastric, phenotype (MUC5AC++, MUC6+, MUC2+, CD10-). Positive p53 immunoreactivity was detected in the carcinoma component of the lesion with a point mutation (G877T; R209I) of the gene and microsatellite instability of the BAT-RII locus; however, immunoreactivity of the mismatch repair gene product hMLH1 was well preserved in the cancer as well as in the hyperplastic lesion. The hyperplastic lesion with serrated glandular pattern would be a precancerous lesion of adenocarcinoma of the stomach.

Phosphatase activity of nuclear PTEN is required for CDX2-mediated intestinal differentiation of gastric carcinoma.

The PTEN tumor suppressor localizes predominantly to the cytoplasm, where it negatively regulates the phosphatidylinositol 3-kinase-AKT signaling pathway; however, the biological significance of nuclear PTEN in gastric carcinoma (GC) remains unknown. In this study, transduction of recombinant PTEN into GC-derived TMK-1 cells promoted PTEN nuclear localization with increased mRNA levels of CDX2 and intestinal claudins (CLDN3 and CLDN4), whereas the G129E phosphatase 'dead' mutant had no effect. In GC tissue samples, tumors with nuclear PTEN expression frequently demonstrated the intestinal-type claudin phenotype. Our results suggested that nuclear localization of PTEN is important for determining intestinal differentiation of GCs.

Prognostic significance of intestinal claudins in high-risk synchronous and metachronous multiple gastric epithelial neoplasias after initial endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is useful in en bloc curative resection and enables patients with early gastric carcinoma (GC) to have a better quality of life. But metachronous recurrence of GC at other sites in the stomach has become a major issue after initial ESD. The purpose of the present paper was to examine gastric (claudin-18) and intestinal claudin (claudin-3 and claudin-4) expression in early GC on immunohistochemistry to clarify the association with clinicopathology, mucin phenotypes, microsatellite instability (MSI) status and the incidence of synchronous and metachronous gastric epithelial neoplasias after initial ESD. According to intestinal claudin expression, a total of 73 early GC were divided into two groups: intestinal claudin-positive (I-CLDN(+)) phenotype (n = 52; 71%); and intestinal claudin-negative (I-CLDN(-)) phenotype (n = 21; 29%). Although no significant association was found with clinicopathology and the MSI status, the I-CLDN(+) early GC correlated with the mucin phenotypes and had a significantly higher incidence of synchronous and metachronous multiple GC and gastric adenomas (P = 0.049). These results indicate that early GC demonstrating I-CLDN(+) phenotype have a high risk of synchronous and metachronous secondary gastric epithelial neoplasias.

Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma.

According to the expression of gastric (claudin-18) and intestinal claudins (claudin-3 and claudin-4), the authors have previously proposed a new phenotypic classification of gastric carcinoma (GC): the gastric (G-CLDN), intestinal (I-CLDN) and unclassified claudin (U-CLDN) phenotypes. The aim of the present study was to examine the role of Cdx2, the caudal-related transcription factor, on the regulation of intestinal claudins expression in vitro and in vivo. It was confirmed on immunohistochemistry that non-neoplastic gastric mucosa with intestinal metaplasia (IM) expressed Cdx2 with increased levels of intestinal claudin expression. In addition, Cdx2 expression was detected in 28 (30%) of 94 GC at the invasive front. Interestingly, Cdx2 expression had a significant association with the I-CLDN phenotype (P < 0.001), which was almost identical to the established gastric and intestinal mucin-based GC classification. Furthermore, the transfection of a recombinant human CDX2-expressing vector into TMK-1 (Cdx2-negative) GC cells specifically elevated the expression of claudin-3 and claudin-4 at the mRNA (CLDN3, 3.9-fold; CLDN4, 2.8-fold) and protein levels (claudin-3, 8.6-fold; claudin-4, 9.8-fold), whereas no induction of the other claudins was detected. These findings suggest that Cdx2 plays an important role in the regulation of intestinal claudin expression not only in gastric mucosa with IM but also GC.