Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases.

BACKGROUND: The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured. PATIENTS AND METHODS: This study was carried out with the participation of 14 facilities in Japan, and 2283 samples were collected. The subjects with bile acid concentrations equal to or higher than the limit of detection were divided into four groups of equal size (group A: 0-25%, group B: 26-50%, group C: 51-75%, and group D: 76-100%). Thus, including the control group, there were five groups in total. The odds that the control group would develop atrophic gastritis and intestinal metaplasia was set as 1,and the odds ratios (OR) in groups A, B, C and D were calculated based on the odds in the control group. RESULTS: Regarding the development of atrophic gastritis, no increased risk was observed in either the Helicobacter pylori (H. pylori)-positive or -negative cases. The OR for the development of intestinal metaplasia were significantly higher, for both cases with and without H. pylori infection, in group D. CONCLUSION: High concentrations of bile acid seem to be associated with an elevated risk of intestinal metaplasia.

Endoscopic submucosal dissection for early gastric cancer using a cross-counter technique.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) in early gastric cancer has rapidly come into widespread use. However, since complications such as bleeding and perforation often occur, and the procedure time is longer for ESD than endoscopic mucosal resection (EMR), development of safer and more reliable technique is required. PATIENTS AND METHODS: The subjects comprised 45 patients with lesions diagnosed histologically as early gastric cancer. They were divided into three groups: cross-counter technique group (CC, n = 15), peroral traction-assisted ESD with suture material group (PT, n = 15), and no-traction group (NT, n = 15). ESD was carried out by two endoscopists who had experienced fewer than 30 cases of ESD. To compare safety and efficacy of a new traction method (CC group) for ESD in early gastric cancer with other methods (PT group and NT group), procedure time, dissected area per unit time, complete resection rate, perforation rate, and bleeding rate were evaluated. RESULTS: There was no significant difference among these three groups in terms of complications, complete resection rate or procedure time. The dissection area per unit time was 22.4, 15.7, and 13.5 mm(2)/min in the CC, PT, and NT groups, respectively, and there was a significant difference between the CC and NT groups (p = 0.007). CONCLUSIONS: The cross-counter technique shortened the treatment time for endoscopists without abundant experience in gastric ESD, and it is considered a useful method to institute in order to introduce ESD.

Endoscopic ablation therapy for gastrointestinal superficial neoplasia.

AIM: In Japan, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been widely accepted and standardized for the treatment of gastrointestinal superficial neoplasia. METHODS: In contrast, mucosal ablation techniques are more common in Western countries and a variety of endoscopic ablation modalities, including argon plasma coagulation (APC), photodynamic therapy (PDT) and lasers, are used. RESULTS: Recently developed modalities such as radiofrequency ablation (RFA) and cryotherapy are also available for the treatment of superficial lesions such as dysplasia of Barrett's esophagus. CONCLUSION: Although we should understand that the completeness of destruction of neoplastic tissue can only be judged at follow up, endoscopic ablation is a viable alternative to endoscopic resection for dysplasia and early-stage malignancies, especially for poor candidates of surgery or endoscopic resection.

[Successful rituximab monotherapy in a patient with mucosa-associated lymphoid tissue lymphoma of the rectum with trisomy 3, 18].

A 62-year-old man was referred to our hospital with enlargement of mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum after the eradication of Helicobacter pylori. The patient was given a diagnosis of stage I MALT. Endoscopic observation revealed an enlarged rectal tumor with 3, 18 double trisomy. Rituximab monotherapy was given and complete remission was achieved. Rituximab monotherapy can be useful for MALT lymphoma of the rectum.

Ultrasonographic comparison of gastric motility between diabetic gastroparesis patients with and without metabolic syndrome.

BACKGROUND AND AIMS: Diabetic patients with poor glycemic control or long standing disease often have impaired gastric motility. Recently, metabolic factors such as blood glucose have been reported as influencing gastric motility independently of autonomic neuropathy. Many diabetic patients have metabolic syndrome, which is strongly associated with coronary and other diseases. We investigated whether metabolic syndrome influences diabetic gastroparesis patients. METHODS: We observed gastric motility ultrasonographically in diabetic gastroparesis patients including nine with and nine without metabolic syndrome. Both groups complained of upper abdominal symptoms when hospitalized to improve blood sugar control. All patients underwent upper gastrointestinal endoscopy to rule out gastric and duodenal lesions. All had autonomic neuropathy. Gastric motility was evaluated within 3 days after admission by transabdominal ultrasonography after a test meal. RESULTS: Gastric emptying was 45.0 +/- 13.7% in patients with and 39.1 +/- 11.9% in patients without metabolic syndrome, which was not statistically significant. Frequency of gastric contractions was 8.33 +/- 2.78 per 3 min in patients with metabolic syndrome and 7.44 +/- 2.13 per 3 min in the others, which was not statistically significant. The motility index, which involves antral contractility, was 3.21 +/- 2.18 in patients with metabolic syndrome and 2.80 +/- 1.87 in the others, which was not statistically significant. CONCLUSIONS: Metabolic syndrome did not appear to contribute to delayed gastric motility in diabetic gastroparesis.

[Cancer chemoprevention-basic and clinical aspects].

Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis, and was proposed in the United States in view of the cost-benefits. Since recent progress in molecular biology revealed several signal transduction routes in carcinogenesis, the search for mechanism-based chemopreventive agents is under way. Many chemopreventive clinical trials for various cancers including colorectal cancer, prostate cancer and breast cancer, have been performed. Chemoprevention to eradicate viruses or bacteria such as hepatitis viruses or Helicobacter pylori is also important in order to prevent development of cancer.

Relationship between mucin expression and preoperative bile juice cytology in biliary tract carcinoma.

The present study evaluated correlations between preoperative bile juice cytology and mucin expression of surgical specimens in biliary tract carcinoma. Twenty-five patients with biliary tract carcinoma surgically treated at our hospital, whose bile juice cytology had been evaluated before operation, were allocated to this study. Biliary cytology was classified into three categories based on the Papanicolaou classification. Immunohistochemical staining of tissues was performed using MUC1 and MUC2 monoclonal antibodies. Lesions showing MUC1 expression of ++ or higher and MUC2 expression of - were classified as Group A, and the remaining lesions as Group B. According to the epithelial site, preoperative cytology was highly correlated in Group A, while it was negative in Group B (p<0.05). In the advanced site of carcinomas, preoperative cytology tended to highly be positive in Group A, while it tended to be negative in Group B (p<0.05). These results suggest that the bile juice cytology results are affected by characteristics of mucin expression in the tissue. Based on the possibility that mucin expression correlates with the prognosis of each carcinoma, a positive cytological result suggests a poor prognosis for the carcinoma, which may be informative for predicting the post-operative courses and choosing treatments.

Evaluation of serum amylase and gabexate mesilate with endoscopic papillary balloon dilatation.

Gabexate mesilate (GM) relaxes the papilla of Vater in addition to inhibiting the several proteases. We evaluated whether prophylactic administration of GM would prevent the occurrence of acute pancreatitis in endoscopic papillary balloon dilation (EPBD). Nineteen patients with common bile duct stones were separated into two groups according to the admission year. The group A has been administered GM intravenously at 2mg/kg/hr after EPBD till six hours later, and the group B has been administered GM before fifteen minutes of EPBD till six hours later. The mean value of sphincter of Oddi (SO) basal and peak pressure in the group B was significantly lower than that in the group A, moreover the mean value of the pancreatic pressure in the group B was significantly lower than that in the group A. However two cases had mild acute pancreatitis in the group B. GM loosened SO and pancreatic duct pressure by direct stimulation of SO, although it could not have enough effect to prevent the acute pancreatitis in EPBD.

[A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy].

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.

A patient with esophageal hemangioma treated by endoscopic mucosal resection: a case report and review of the literature.

In a 58-year-old male, upper digestive endoscopy revealed a protruding lesion in the esophagus on a medical examination. The patient was referred to the Department of Surgery in our hospital to undergo surgery. On the initial consultation, upper digestive endoscopy showed a smooth, soft, black purple, type II protruding lesion measuring approximately 25 mm at 35 cm apart from the incisor. For diagnostic treatment and patient's request, endoscopic mucosal resection (EMR) was performed. The resected specimen measured 25 mm x 25 mm. The histological findings suggested cavernous hemangioma. To treat esophageal hemangioma, esohagectomy, tumor enucleation, or sclerotherapy has been performed. However, recently, thorough preoperative examination, such as endoscopic ultrasonography (EUS), has facilitated endoscopic resection, such as EMR.

Ultrasonographic assessment of gastric motility in diabetic gastroparesis before and after attaining glycemic control.

BACKGROUND: Glycemic control is important for maintaining gastric motility in diabetic patients, but gastric motility has not yet been studied ultrasonographically in relation to glycemic control. METHODS: We made such observations before and after establishing glycemic control in diabetic patients with gastroparesis. We studied 30 diabetic patients with upper abdominal digestive symptoms who were hospitalized for correction of poor blood sugar control and who underwent upper digestive tract endoscopy to rule out structural causes such as gastric/duodenal lesions. Gastric motility was evaluated by transabdominal ultrasonography, using a test meal, before and after attainment of glycemic control (within 3 days after admission and 3 days before discharge). Also, upper abdominal digestive symptoms present on admission and at discharge were compared. RESULTS: After glycemic control was established, contractions of the antral region were more frequent than before the attainment of control (8.93 +/- 1.17/3 min vs 7.63 +/- 2.22/3 min, respectively; P < 0.001). Glycemic control also significantly improved gastric emptying (before glycemic control, 49.2 +/- 14.8%; after, 67.1 +/- 11.5%; P < 0.001). This was also true for the motility index, concerning antral gastric contractility (before control, 2.97 +/- 1.57; after, 3.75 +/- 1.09; P < 0.05). Upper abdominal symptom scores were also significantly lower after attainment of control than before (0.47 +/- 0.78 vs 3.17 +/- 2.00, respectively; P < 0.001). CONCLUSIONS: These findings suggest that attaining glycemic control improves gastric motility and attainments upper abdominal symptoms in diabetic patients with gastroparesis.

Colorectal xanthomas with polypoid lesion: report of 25 cases.

Little attention has been paid to colorectal xanthoma. To clarify the clinical and pathological features of colorectal xanthoma, we report 28 colorectal xanthomas biopsied from 25 patients. All were composed of typical xanthoma cells and showed polypoid configuration. Median age of the patients was 64 years and there were 15 men and 10 women. Diabetes mellitus, constipation, and hyperlipidemia were found in two, one, and seven patients, respectively. Seventeen (60.7%) of the 28 polyps were located in the sigmoid colon and the remaining 11 in the rectum. Twenty-three polyps (82.1%) were sessile. Twelve (60.0%) of twenty polyps that were recorded were reddish in color. Only two polyps revealed a yellowish tone. Microscopically, foamy cells were present in the lamina propria, but the submucosa did not contain foamy cells. Immunohistochemically, the foamy cells invariably expressed extensive positivity for CD68. The colonic glands showed a deformity in the case with moderate to intense density of the foamy cells. The surface epithelium showed a hyperplastic change in 22 (78.6%) xanthomas. The colonic glands in four xanthomas were also associated with hyperplastic changes. The basement membrane of the surface epithelium was often thickened. Cell debris and proliferation of the capillaries were observed just below the surface epithelium in 19 (67.9%) and 22 (78.6%) xanthomas, respectively. Previous mucosal minute injury was suggested as the pathogenesis of colorectal xanthomas. Colorectal xanthomas were not identical to gastric and esophageal xanthoma, endoscopically or microscopically. We prefer the term "xanthomatous polyp" rather than xanthoma in the colorectal region. They may be regarded as a novel type of colorectal non-neoplastic polyp.

Clinical value of the determination of serum guanase activity in patients with chronic hepatitis type C.

The study examines the clinical significance of guanase (GU) measurement in patients with hepatitis C. 688 patients in whom either ALT was abnormal, or in whom HBsAg or HCVAb was detected in the serum, were enrolled into this study. The percentage of cases in which normal ALT while elevated GU was compared among the different disease groups. Then, the percentage of cases with normal ALT but elevated GU was compared between HBV and HCV groups. For the entire population, a significant correlation was observed between ALT and GU (r=0.872). The overall percentage of cases with normal ALT but elevated GU activity was 11.4%. In HCV group, 449 cases had normal ALT. Of these cases, 20.3% had elevated GU, while ALT was normal. Before 1989, no test to check donated blood for HCV antibody was available. However, screening of donated blood for high GU was associated with a reduced incidence of post-transfusion hepatitis. This is probably because following the screening, blood donated by patients with hepatitis C who had normal ALT but elevated GU was rejected. After the introduction of HCV antibody measurement, GU measurement is still useful to reveal the pathophysiological condition in-patients with chronic hepatitis type C.

A treatment using STI571 for jejunal gastrointestinal stromal tumor (GIST) accompanied with liver metastasis and peritoneal dissemination.

A 64-year-old man with a chief complaint of melena visited our emergency outpatient clinic. After several examinations, he was diagnosed as a gastrointestinal stromal tumor (GIST) with liver metastasis. Surgical resection of the jejunal lesion and postoperative adjuvant therapy with STI571 for one year was performed. Due to recent immunohistological studies and introduction of STI571, the diagnosis, treatment, and prognosis of GIST are about to change profoundly. Further accumulation of cases is necessary to investigate the diagnosis, treatment, and prognosis of GIST.

A pedunculated submucosal lesion in the stomach with inverted downgrowth.

A 70-year-old man with a gastric lesion was referred to our hospital because of an unusual pedunculated lesion in the gastric body. Endoscopic ultrasound showed scattered cystic lesions within a heterogeneous area confined to the submucosal layer. Endoscopic mucosal resection was performed to obtain a precise diagnosis, as well as for removal. The lesion was histopathologically diagnosed as a heterotopic submucosal gland. We herein describe this rare type of gastric polyp and provide a literature review.

A mechanism for abnormal angiogenesis in human radiation proctitis: analysis of expression profile for angiogenic factors.

BACKGROUND: Radiation proctitis is an increasingly prevalent problem, with many patients being treated with radiotherapy for pelvic cancers. However, the mechanisms by which radiation proctitis develops in humans are not well understood. In this study, the expression profiles of angiogenic factors were analyzed to clarify their role in the etiology of radiation proctitis. METHODS: Rectal biopsies were taken from 8 patients with radiation proctitis and 8 normal subjects. Protein lysates of the tissues were applied to an antibody array for angiogenesis-related factors. The mRNA level of each factor was evaluated by Taqman real-time PCR. Immunohistochemistry was performed using the labeled streptavidin biotin method. RESULTS: Antibody array analysis revealed 2.12- to 7.31-fold higher expression levels of angiogenin, fibroblast growth factor 1 (FGF1), endoglin, matrix metalloproteinase (MMP)-8, urokinase-type plasminogen activator (uPA) and maspin in radiation proctitis tissues compared with normal rectal mucosa. The mRNA level of each factor in radiation proctitis tissue was significantly higher than in normal rectal mucosa, suggesting their transcriptional activation. Immunohistochemical staining showed strong expression of angiogenin and maspin in rectal epithelia, MMP-8 and uPA in infiltrating lymphocytes, FGF1 in fibroblasts and endoglin in endothelial cells. The expression of VEGF was not evident. CONCLUSIONS: Our results suggest that in radiation proctitis, MMP-8 and uPA cooperatively degrade the extracellular matrix and basement membrane to provide space for angiogenesis. Simultaneously, angiogenin and FGF1 promote endothelial cell proliferation, and endoglin induces vessel formation, culminating in angiogenesis. Inhibitors of angiogenic factors such as angiogenin and FGF1 may be effective for treating radiation proctitis.

Migrated endoclip and stone formation after cholecystectomy: a case treated by endoscopic sphincterotomy.

Endoclip migration into the common bile duct following laparoscopic cholecystectomy (LC) is an extremely rare complication. Migrated endoclip into the common bile duct can cause obstruction, serve as a nidus for stone formation, and cause cholangitis. We report a case of cholangitis due to a migrated endoclip and consequent choledocholithiasis 6 years after LC, which was successfully treated by endoscopic extraction.

Infrared fluorescence endoscopy for the diagnosis of superficial gastric tumors.

BACKGROUND: Indocyanine green (ICG) is a fluorescent marker that is excited by rays at a wavelength of 768 nm to emit fluorescence at a wavelength of 807 nm in the infrared (IR) range. We developed an IR fluorescence endoscope (IRFE) to observe superficial gastric tumors and assessed its clinical usefulness. OBJECTIVE: To evaluate the clinical usefulness of an IRFE for the assessment of superficial gastric tumors. DESIGN: An observational study. SETTING: University hospital. INTERVENTIONS: Newly developed IRFE. PATIENTS: Thirty patients with gastric tumors were enrolled in this study, and their lesions were subjected to endoscopic submucosal dissection (ESD), or laparoscopic gastrectomy after observation with the IRFE. METHODS: Gastric lesions were subjected to conventional observation, followed by IR fluorescence observation before and after intravenous ICG (0.01 mg/kg) injection. MAIN OUTCOME MEASUREMENTS: The relationship between the positive fluorescence and invasivity of each tumor. RESULTS: Fluorescence was positive in 8 of 10 gastric cancers with submucosal invasion (80%) and 1 of 20 adenomas or intramucosal gastric cancers (5%); the difference was statistically significant (P<.01). CONCLUSION: IRFE is a useful diagnostic tool for estimating the invasivity of gastric tumors.

Evaluation of solitary and scattered esophageal varices according to infrared endoscopy and endoscopic ultrasonography.

BACKGROUND AND AIM: The aim of this study was to clarify the etiology and clinical significance of solitary and scattered esophageal varices by evaluating their hemodynamics and other characteristics using infrared endoscopy and endoscopic ultrasonography. METHODS: The study group comprised 44 lesions of these two related types detected in 28 patients by visible-light endoscopy. Infrared endoscopy was used to characterize blue-black coloration before and after rapid intravenous injection of indocyanine green (2 mg/kg). During endoscopic ultrasonography, depth within the esophagus and echo patterns of these varices were characterized. RESULTS: Diameters of these varices were significantly smaller in lesions more strongly staining by infrared endoscopy. Lesion diameter was significantly smaller in varices showing homogeneous low echogenicity than in those showing mixed echogenicity. Lesions showing homogeneous high echogenicity stained most weakly followed in turn by lesions with mixed echogenicity and finally those showing homogeneous low echogenicity. CONCLUSION: Indocyanine green injection was useful for infrared observation of the hemodynamics of solitary and scattered esophageal varices, as was endoscopic ultrasonography in defining the location and morphology of these lesions. Varices with larger diameters stained more persistently when hemodynamics were evaluated by infrared endoscopy, and often showed a mixture of low and high echogenicity by endoscopic ultrasonography. These observations suggest that blood flow in the varices is slowed, and that the risk of hemorrhage increases with increased diameter especially with uniform enhancement and uniform echogenicity.