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'.

N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.

The Wiskott-Aldrich syndrome protein (WASP) family of molecules integrates upstream signalling events with changes in the actin cytoskeleton. N-WASP has been implicated both in the formation of cell-surface projections (filopodia) required for cell movement and in the actin-based motility of intracellular pathogens. To examine N-WASP function we have used homologous recombination to inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos survive beyond gastrulation and initiate organogenesis, they have marked developmental delay and die before embryonic day 12. N-WASP is not required for the actin-based movement of the intracellular pathogen Listeria but is absolutely required for the motility of Shigella and vaccinia virus. Despite these distinct defects in bacterial and viral motility, N-WASP-deficient fibroblasts spread by using lamellipodia and can protrude filopodia. These results imply a crucial and non-redundant role for N-WASP in murine embryogenesis and in the actin-based motility of certain pathogens but not in the general formation of actin-containing structures.

Sludge and stone formation in the gallbladder in bedridden elderly patients with cerebrovascular disease: influence of feeding method.

PURPOSE: The incidence of gallbladder sludge or gallstone formation in bedridden patients with cerebrovascular disease (CVD) remains obscure. The aim of this study was to determine the incidence, relationship to feeding method, and mechanisms of gallbladder sludge and gallstone formation in elderly patients with CVD. METHODS: Using ultrasonography, we determined the development of gallbladder sludge and gallstone over a 12-month period, the area of the gallbladder, the gallbladder contractile response to cerulein, and fasting levels of plasma cholecystokinin (CCK) in 40 bedridden elderly patients with CVD. The patients were divided into three groups based on the feeding method: oral ingestion (OI), nasogastric feeding (NF), and total parenteral nutrition (TPN). RESULTS: Gallbladder sludge and gallstone were not observed in any of the 14 OI patients, but occurred in 6 and 1 of the 11 NF patients, and in 14 and 3 of the 15 TPN patients, respectively. Fasting gallbladder areas were significantly larger in the TPN group than in the other two groups. The TPN group showed a marked decrease in cerulein-induced gallbladder contractility. Fasting plasma CCK levels were lower in the TPN group than in the OI group. CONCLUSIONS: Our results indicate that elderly patients with CVD confined to bed over long periods are not necessarily at risk of gallbladder sludge or gallstone formation, and the development of these features may be associated with the feeding method. The predisposition of CVD patients on TPN to gallbladder disease is probably caused by failure of gallbladder contraction, resulting from insufficient secretion of CCK and impaired sensitivity of the gallbladder to CCK.

Progressive systemic sclerosis associated with primary small cell carcinoma of the stomach.

A 64-year-old man with a 5-year history of progressive systemic sclerosis (PSS) was hospitalized because of melena. Radiological and endoscopic examinations showed an ulcerative lesion with sharply demarcated and raised margins in the fornix of the stomach. Tumor markers--serum carcinoembryonic antigen (CEA, 11.3 mg/ml) and neuron-specific enolase (NSE, 38.9 ng/ml) were elevated. Histological examination of endoscopic biopsy specimens (and of necropsy specimens) showed proliferation of atypical small round cells. Immunohistological examination of these cells showed they were positive for epithelial membranous antigen (EMA), and neuron-specific enolase (NSE), but negative for UCHL1, leukocyte common antigen (LCA), anti-leukocyte B-cell (MB1), and anti-leukocyte T-cell (MT1) antigens. Based on these histological and immunohistological tests, a definite diagnosis of small cell carcinoma of the stomach with PSS was established. Our case is a rare combination of PSS and gastric small cell carcinoma. We also reviewed the literature for the association between PSS and gastric cancer in Japanese patients.

Acinar cell carcinoma of the pancreas associated with hypoglycemia: involvement of "big" insulin-like growth factor-II.

Apart from insulinomas, pancreatic tumors are rarely complicated by hypoglycemia and some may produce insulin-like growth factor II (IGF-II). To our knowledge, IGF-II-producing pancreatic tumors associated with hypoglycemia have not been reported previously. We describe what we believe to be the first case of "big" IGF-II-producing pancreatic acinar cell carcinoma. A 68-year-old man presented with a history of recurrent hypoglycemia. Abdominal computed tomography scan and magnetic resonance imaging showed a mass, approximately 5 cm in diameter, in the tail of the pancreas and two low-density areas in the liver. Low serum glucose was associated with low insulin levels and high levels of hormones (i.e., glucagon and IGF-II) that are functionally opposite to insulin. Although serum IGF-II level was within the normal range, most IGF-II was of the high molecular weight form, as determined by Western immunoblot analysis. Based on these findings, a diagnosis of hypoglycemia induced by IGF-II-producing pancreatic tumor was made. Surgery was not possible because of the patient's poor general condition. The patient ultimately died as a result of malignant cachexia. At autopsy, a yellowish-white tumor was found in the tail of the pancreas, and a histopathologic diagnosis of acinar cell carcinoma was made. Immunohistologically, the tumor cells contained IGF-II in an irregular staining pattern, suggesting that the hypoglycemia was caused by a pancreatic tumor producing "big" IGF-II.

Low prevalence of Helicobacter pylori in individuals with HTLV-I infection.

BACKGROUND: The prevalence of Helicobacter pylori in HIV-positive individuals is significantly lower than in HIV-negative controls. However, its prevalence in individuals infected with human T-cell leukaemia virus type I (HTLV-I), another important member of the human retrovirus family, has not been previously investigated. OBJECTIVE: To establish the prevalence of H. pylori in HTLV-I-positive individuals in the Nagasaki Prefecture, which is an area endemic for HTLV-I. METHODS: We examined sera from 146 HTLV-I-positive individuals with a mean age of 56.7 years, consisting of 45 adult T-cell leukaemia (ATL) patients, 13 HTLV-I-associated myelopathy (HAM) patients and 88 healthy carriers. Serum samples of 292 age- and sex-matched HTLV-I-negative controls were also examined. Serum anti-H. pylori immunoglobulin (Ig) G antibody was examined using an enzyme-linked immunosorbent assay kit. Twenty-eight HTLV-I-positive patients were examined endoscopically, assessed for H. pylori by culture, histology and CLO test using gastric biopsy specimens, and gastritis in these patients was also graded histologically. RESULTS: The seroprevalence of H. pylori was 48% in HTLV-I-positive individuals versus 64% in HTLV-I-negative controls (P < 0.01). In the three HTLV-I-positive groups, ATL patients and carriers had significantly lower seroprevalence of H. pylori than the HTLV-I-negative controls (P < 0.05). Assessment of H. pylori using gastric biopsy specimens also showed a significantly lower prevalence of H. pylori infection in HTLV-I-positive patients than controls (46% versus 70%, P < 0.05). Histological examination showed a significantly higher degree of activity, inflammation and glandular atrophy in the antrum and corpus in H. pylori-positive patients compared to H. pylori-negative patients. H. pylori-positive patients with HTLV-I infection had a more severe degree of glandular atrophy in the corpus than H. pylori-positive controls without HTLV-I infection. CONCLUSION: We have found a reduced prevalence of H. pylori in HTLV-I-positive individuals. Whatever the explanation, infection with HTLV-I does not predispose to the risk of H. pylori infection.

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.

Hydronephrosis caused by a left renal vein in a patient with horseshoe kidney: a case report.

We report a rare case of hydronephrosis secondary to ureteropelvic stenosis caused by a branch of the left renal vein in horseshoe kidney. We were unable to determine the etiology of hydronephrosis of the horseshoe kidney by means of radiological images. When radiological images fail to show any etiology of hydronephrosis in horseshoe kidney, the possibility of compression of the ureteropelvic junction by a branch of the renal vein should be borne in mind, and re-assessment of the venous phase of angiography and evaluation by coronal or sagittal images of MRI is recommended.

Effect of intrarectal prostaglandin E2 analogue (enprostil) on trinitrobenzenesulphonic acid-induced colitis in rats.

Prostaglandins exert a protective effect on colonic mucosa in experimentally induced colitis. This study investigated the effect of enprostil, a prostaglandin E2 (PGE2) analogue, on trinitrobenzenesulphonic acid (TNBS)-induced colitis in rats. Each rat received a rectal enema containing TNBS (30 mg), followed 24 h later by intrarectal once-daily enprostil (200 microg). Enprostil-treated and control rats were killed on day 3 (enprostil group, n = 5; control, n = 6) or day 10 (enprostil group, n = 5; control, n = 5) after TNBS treatment. The area of damaged mucosa of the colon was measured relative to the total colonic area. We also determined the macroscopic score of mucosal damage, and measured PGE2, 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2) concentration in portal vein blood samples. Enprostil significantly reduced both the area of damaged mucosa (including the ulcer area) and the macroscopic score after 3 days' treatment compared with control. Similarly, enprostil significantly reduced plasma concentration of PGE2, 6-keto-PGF1alpha and TXB2 during the acute phase at day 3 of treatment compared with control, but not at day 10. These results suggest that PGE2 enema may have therapeutic potential for treating patients with proctitis or left-sided colitis.

Micronutrient status and glutathione peroxidase in bedridden patients on tube feeding.

Deficiency of micronutrients, especially selenium, is common in critically ill patients. We investigated the micronutrient status (selenium, zinc, copper and manganese) and glutathione peroxidase (GSH-Px) activity in 30 tube-fed patients and 21 hospitalized non-tube-fed control patients. Serum levels of selenium, copper and manganese in tube-fed patients were significantly lower than in control patients (selenium: 4.85+/-1.38 microg/dl versus 8.67+/-1.45 pg/dl; copper: 44.7+/-36.9 microg/dl versus 92.1+/-21.2 microg/dl; manganese 0.59+/-0.41 microg/dl versus 1.52+/-0.59 microg/dl). However, zinc and log GSH-Px in the serum were similar in the two groups. Serum selenium concentration correlated with the daily intake of selenium in tube-fed patients, but zinc, copper and manganese concentrations did not correlate with the daily intake of the respective trace elements in tube-fed patients. Blood GSH-Px activity correlated positively with serum selenium concentrations in the control patients, but not in tube-fed patients. These results demonstrate that selenium content of enteral feed appears to be insufficient to maintain normal serum levels in elderly bedridden patients. Our findings emphasize the importance of monitoring micronutrient status in patients on enteral feeding to avoid trace element deficiencies.

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.

Comparison of the microbicidal activities of superoxidized and ozonated water in the disinfection of endoscopes.

The microbicidal activities of superoxidized water (electrolysed strong acid water [ESAW] or electrolysed weak acid water [EWAW]), ozonated water, 0.05% chlorhexidine and 2% glutaraldehyde were tested against seven strains of clinical micro-organism isolates. Following incubation of bacterial suspensions in ESAW and EWAW for 10 s, the number of micro-organisms was reduced below the detection limit. The microbicidal activities of ESAW and EWAW were similar to that of glutaraldehyde, and superior to ozonated water and 0.05% chlorhexidine. The microbicidal activities of ESAW, EWAW and ozonated water were markedly diminished in the presence of albumin. Microbial contamination of upper gastrointestinal endoscopes was detected after 90 endoscopic procedures, but treatment of the endoscope with ESAW, EWAW or ozonated water eradicated the microbes. These results indicate that ESAW and EWAW are effective disinfectants after mechanical cleaning of upper gastrointestinal endoscopes, and can, therefore, be used in the endoscopy unit.

Polymorphism of CYP2C19 and gastric emptying in patients with proton pump inhibitor-resistant gastric ulcers.

The aim of the present study was to investigate whether CYP2C19 polymorphism status and gastric emptying are related to healing in patients with gastric ulcers. We studied the CYP2C19 status in seven patients with proton pump inhibitor (PPI)-resistant ulcers, 21 with PPI-sensitive ulcers and 46 healthy volunteers using polymerase chain reaction restriction fragment length polymorphism to detect CYP2C19m1 mutation in exon 5 and CYP2C19m2 mutation in exon 4. Gastric emptying was evaluated using the 13C-acetate breath test. The frequency of phenotypes, indicated by genotypes, did not differ significantly between the three patient groups. The peak time of 13C excretion in patients with PPI-resistant ulcers was significantly longer than that of patients with PPI-sensitive ulcers and healthy volunteers. Our results suggest that rate of gastric emptying, but not CYP2C19 polymorphism, is likely to be an important factor in the delayed healing of patients with PPI-resistant gastric ulcer.