Significance of background coloration in endoscopic detection of early esophageal squamous cell carcinoma.

Endoscopic diagnostics of early squamous cell carcinoma (SCC) in the laryngo-esophageal region have dramatically improved together with development of less invasive endoscopic treatment. It is essential for gastrointestinal endoscopists to detect lesions when they are still endoscopically treatable, especially in this region since surgical approach can still be extremely invasive. Pioneers have found some notable fundamental alterations in early SCC and created several classifications. Inoue [Dig Endosc 2001;13(suppl): 40-41] proposed the intrapapillary capillary (IPCL) classification, which focused on the microvascular change of the mucosal surface. One of the significances of this classification is that it clearly distinguished the lesions that require further pathological evaluation by categorizing the diameter change of the IPCLs. On the other hand, Arima et al. [Esophagus 2005;2:191-197] advocated the alteration of microvessels as well as change of the vascular arrangement in the area. Most recently, the Japan Esophageal Society constructed a new classification uniting these two exemplary classifications as the 'Japanese Classification of Magnifying Endoscopy for Early Squamous Cell Carcinoma'. This classification was intended to be simple and easily applicable in general clinical practice. Brownish color change between the IPCLs has reported to be one of the useful findings in distinguishing early SCC from benign changes such as inflammatory change and low-grade intraepithelial neoplasia. Nevertheless, the exact cause of this phenomenon remains unclear. We recently examined the association of color change with hemoglobin (Hb) in cancer tissue, since NBI exclusively detects the wavelength of Hb in superficial vessels in the gastrointestinal tract. This review article also describes our examination of a distinct finding in esophageal cancer, namely, 'background coloration'.

Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis: a prospective study report.

Rebamipide has a broad spectrum of pharmacological actions that include suppression of neutrophil functions and stimulation of mucosal epithelial cell regeneration by increasing the expression of epithelial growth factor (EGF) and the EGF receptor. Sixteen patients with active ulcerative colitis (UC; mild in 1 patient, moderate in 11, and severe in 4) were recruited. Enemas containing 150 mg rebamipide per dosing were administered during the daytime after passage of stool, twice a day for 4 weeks. UC disease activity index (UC-DAI), endoscopic activity index (EAI), and Floren's grading (FG) of mucosal biopsy specimens were measured at entry and at 4 weeks. Five of 16 patients did not complete the study, and therefore, final efficacy assessment was done on 11 patients who completed the 4 weeks of treatment. Improvements were observed in UC-DAI (P = 0.0049), EAI (P = 0.0043), and FG (P = 0.0084). There was no serious rebamipide-related side effect in any of the 16 patients. In conclusion, rebamipide topical therapy appears to be effective for the treatment of mildly to moderately active distal UC. Further controlled studies are warranted for this promising drug.

Ghrelin enhances gastric motility through direct stimulation of intrinsic neural pathways and capsaicin-sensitive afferent neurones in rats.

BACKGROUND: Ghrelin may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not yet been clearly defined. The present study was designed to investigate whether ghrelin accelerates gastric emptying via capsaicin-sensitive afferent neurones and directly affects the enteric neuromuscular function. METHODS: Gastric emptying of nutrient solids was assessed after intravenous administration of saline or ghrelin in conscious rats. The effects of ghrelin on gastric emptying were also examined in rats pretreated with capsaicin. Gastric emptying and intestinal transit of non-caloric liquids were evaluated using 51Cr solution. The effects of ghrelin on spontaneous contractile activities of isolated strips from stomach and jejunum were also investigated and the influence of ghrelin on motor responses to carbachol and electrical field stimulation was examined. RESULTS: Ghrelin significantly accelerated gastric emptying of both nutrient solids and non-caloric liquids in conscious rats. The intestinal transit of non-caloric liquids was also enhanced by ghrelin. Pretreatment with capsaicin prevented the ghrelin-induced acceleration of gastric emptying of nutrient solids. Ghrelin did not modulate spontaneous and carbachol-induced contractions of strips of gastric body, gastric antrum and jejunum. However, electrical field stimulation-induced contractions were significantly enhanced by ghrelin in the gastric body. CONCLUSIONS: The results suggest that the stimulatory effects of ghrelin on gastric motility are mediated by direct stimulation of the enteric neural pathway and capsaicin-sensitive afferent neurones.

Expression of interleukin 6 and its receptor in human gastric and colorectal cancers.

Interleukin 6 (IL-6) is a pleiotropic cytokine with many physiological functions. The present study was designed to determine the expression of IL-6 and its receptor (IL-6R) in human gastric and colorectal cancers. Nine gastric- and nine colorectal cancer cell lines were analysed. The IL-6 gene was expressed in two gastric cancer cell lines and one colorectal cancer cell line; however, most of the cancer cell lines studied expressed the IL-6R gene. The level of IL-6 secretion in the gastric cancer cell lines correlated with the level of soluble IL-6R secretion, and was significantly higher (< approximately 100 pg/ml) than the level of IL-6 secretion in the colorectal cancer cell lines (< approximately 50 pg/ml). These results suggest that IL-6 may act in a paracrine fashion rather than an autocrine fashion in these cell lines.

Accumulation of mast cells and macrophages in focal active gastritis of patients with Crohn's disease.

BACKGROUND/AIMS: Recent studies have shown that focal active gastritis seems to be the typical gastric pathology in Crohn's disease. The aim of this study was to compare the incidence of focal active gastritis, Helicobacter pylori infection and distribution of gastric mast cells and macrophages in patients with Crohn's disease, ulcerative colitis and H. pylori gastritis without inflammatory bowel disease. METHODOLOGY: Patients with histologically confirmed Crohn's disease (n = 25) or ulcerative colitis (n = 25) and control patients without inflammatory bowel disease (n = 25) were included in this study. Biopsy specimens were obtained from the antrum and corpus of each patient, and stained with hematoxylin and eosin and immunostained using antibodies to tryptase (AA1) and CD68. The number of mast cells and macrophages located in the lamina propria was determined. RESULTS: Focal active gastritis was detected in 54% of H. pylori-negative patients with Crohn's disease, but it was not found in patients with ulcerative colitis nor in the control group. The density of mast cells and macrophages in the lamina propria of H. pylori-positive patients was significantly higher than in H. pylori-negative patients in all groups. In the Crohn's disease group, the number of mast cells (antrum; 83 +/- 11, body; 89 +/- 11/mm2) and macrophages (antrum; 94 +/- 22, body; 92 +/- 17/mm2) in the lamina propria of H. pylori-negative patients with focal active gastritis was halfway between that in H. pylori-positive and H. pylori-negative patients. In focal active gastritis, mast cells accumulated at the border of focal active gastritis, whereas macrophages accumulated in the center of such lesions. CONCLUSIONS: Our findings indicated that the diagnosis of focal active gastritis, using immunostain for mast cells and macrophages, is the histological hallmark of gastric Crohn's disease. Macrophages might be associated with the formation of focal active gastritis in patients with Crohn's disease.

Heterotopic gastric mucosa in intrahepatic bile duct, presenting with hemobilia: a case report.

We present a 66-year-old man with unique heterotopic gastric mucosa in the intrahepatic bile duct causing hemobilia. Endoscopic retrograde cholangiography showed irregular stenosis of the left intrahepatic bile duct, and a provisional diagnosis of cholangiocarcinoma was made. Therefore, partial hepatic lobectomy and cholecystectomy were performed. Histological examination of the liver showed the presence of ectopic gastric mucosa in the intrahepatic bile duct containing mucous glands with parietal and chief cells and bile. Heterotopic gastric mucosa in the intrahepatic bile duct is a rare cause of hemobilia.

Clinical and endoscopic features of adult T-cell leukemia/lymphoma with duodenal involvement.

We describe three cases of adult T-cell leukemia/lymphoma (ATLL) with duodenal involvement and provide a review of the literature. The first case, a 74-year-old woman with acute subtype of ATLL, had multiple polypoid lesions from the bulbus extending into the descending portion of the duodenum. The second case, a 70-year-old man with lymphoma subtype of ATLL, had a polypoid tumor in the descending portion of the duodenum and multiple protruded lesions in the small and large intestines. The third case, a 67-year-old man with lymphoma subtype of ATLL, had a flat-elevated lesion in the descending portion of the duodenum, as well as a gastric ulcerated lesion. Biopsies from these lesions showed mucosal invasion of ATLL cells in each case. All patients received combination chemotherapy, which was successful in the first and third cases, accompanied by the disappearance of gastroduodenal lesions.

Expression of nuclear factor-kappaB in Helicobacter pylori-infected gastric mucosa detected with southwestern histochemistry.

BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) plays a pivotal role in inflammatory responses by upregulating mRNA expression of, for example, proinflammatory cytokines and chemokines. Although in vitro studies have shown that Helicobacter pylori can induce NF-kappaB activation in gastric cancer cell lines, there is little information on cellular localization of NF-kappaB in H. pylori-infected gastric mucosa. METHODS: H. pylori-infected and -negative patients with various endoscopic findings were examined. NF-kappaB expression was studied by means of Southwestern histochemistry, a new method of localizing transcription factors. Labeled double-stranded oligo-DNA with specific consensus sequence for the NF-kappaB binding site was reacted with frozen sections from gastric biopsy specimens. We compared mucosal interleukin-8 (IL-8) and IL-1beta levels as measured with enzyme-linked immunosorbent assay with the degree of NF-kappaB expression. RESULTS: NF-kappaB expression was often evident in nuclei of epithelial cells in H. pylori-infected gastric mucosa. The degree of NF-kappaB expression on the epithelium was significantly more severe in H. pylori-infected than in -negative mucosa. The degree of NF-kappaB expression also correlated with mucosal IL-8 levels but not with IL-8. CONCLUSIONS: H. pylori infection increases the expression of NF-kappaB in gastric mucosa, suggesting that NF-kappaB is involved in inflammatory responses to H. pylori.

Development of hepatocellular carcinoma in a patient with chronic hepatitis C after 6 years of a sustained and complete response to IFN-alpha.

The authors report a rare case of hepatocellular carcinoma (HCC) that developed 6 years after a sustained and complete response to interferon (IFN) therapy for chronic hepatitis C. A 61-year-old Japanese man presented with a mass in the liver that was diagnosed as HCC. Six years earlier he was treated with IFN-alpha and responded successfully to therapy, with sustained normalization of serum aminotransferases and eradication of serum hepatitis C virus (HCV)-ribonucleic acid (RNA). HCV-RNA was also not detected in the resected tumorous and nontumorous liver tissues. The findings suggest that all patients with chronic HCV infection should be followed closely for as long as possible for the potential development of HCC even after a complete and sustained response to IFN treatment.

Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes.

Adult T-cell leukemia (ATL) is a T-cell malignancy caused by human T-cell-leukemia-virus-I (HTLV-I) infection. ATL comprises 4 clinical forms: acute, chronic, smoldering and lymphoma types. ATL is usually resistant to conventional chemotherapy and has a relatively poor prognosis; however, the resistance mechanisms remain undetermined. To explore the multidrug-resistance (MDR) mechanisms of ATL, we examined the expression and functional activity of MDR-related genes in peripheral-blood mononuclear cells (PBMC) from ATL patients by semi-quantitative RT-PCR and FACScan with calcein-AM. PBMC from ATL patients expressed similar or higher levels of MRP, LRP and cMOAT mRNAs, as compared with normal PBMC. In normal controls and ATL patients, MDR1 mRNA expression was undetectable in this study. PBMC from acute and chronic ATL patients expressed significantly higher levels of MRP and LRP mRNA than did normal PBMC (p < 0.01 and p < 0.05 respectively). In chronic ATL, positive correlations were apparent between levels of MRP and LRP mRNA expression (r = 0.759, p = 0.018), and between each mRNA level and the absolute number of abnormal lymphocytes in peripheral blood. Probenecid, an inhibitor of the MRP pump, significantly increased the accumulation of calcein in PBMC from 3 chronic ATL patients. Our findings suggest that the MRP and LRP genes in ATL are often activated by HTLV-I infection and may confer MDR of ATL cells in vivo. Combined chemotherapy with inhibitors of these MDR genes may be promising in the treatment of ATL.

A close relationship between Helicobacter pylori infection and gastric xanthoma.

BACKGROUND: Although the pathogenesis of gastric xanthoma (GX) remains unclear, an association of GX with atrophic gastritis has been reported. Helicobacter pylori is closely related to atrophic gastritis. The aim of this study was to investigate the relationship among GX, H. pylori, and atrophic gastritis. METHODS: Sixty-seven patients with GX were assessed for H. pylori infection by serum anti-H. pylori IgG antibody, in addition to the rapid urease test, culture, and histologic examination using biopsy specimens of the antrum and corpus. The findings were compared with 67 age- and sex-matched control subjects without GX. The distribution of atrophic gastritis was assessed endoscopically. The severity of atrophic gastritis was determined endoscopically and histologically. Serum pepsinogen (PG) levels were also measured. Immunohistochemical staining of GX samples for H. pylori antigen was performed. H. pylori clinical isolates from patients with GX and controls were assessed for cagA by means of polymerase chain reaction. RESULTS: The prevalence of H. pylori was significantly higher in patients with GX than in controls (94% and 72%, respectively). A significantly more extensive atrophic gastritis was present in patients with GX, as determined endoscopically and histologically, than in controls. Serum PG-I levels and the PG-I/PG-II ratio were significantly lower in the GX group than in the control group. H. pylori antigens were frequently identified in the cytoplasm of xanthoma cells in H. pylori-positive specimens of GX (54 of 63 specimens, 86%), whereas no immunoreactivity for H. pylori antigens was detected in H. pylori-negative specimens of GX. There was no significant difference in the positive rate of cagA between the two groups. CONCLUSIONS: Our results identified a close relationship among H. pylori infection, GX, and atrophic gastritis. A proportion of GXs may be provoked by H. pylori infection.