Multicenter feasibility study of bowel preparation with castor oil for colon capsule endoscopy.

BACKGROUND AND AIM: Extensive use of laxatives and incomplete excretion rates are problematic for colon capsule endoscopy (CCE). The aim of the present study was to determine the effectiveness of castor oil as a booster. METHODS: At four Japanese hospitals, 319 examinees undergoing CCE were enrolled retrospectively. Before and after the introduction of castor oil, other preparation reagents were unchanged. RESULTS: Of 319 examinees who underwent CCE, 152 and 167 examinees took regimens with castor oil (between November 2013 and June 2016) and without castor oil (between October 2015 and September 2017), respectively. Capsule excretion rates within its battery life in the groups with and without castor oil were 97% and 81%, respectively (P < 0.0001). Multivariate analysis showed that ages younger than 65 years (adjusted odds ratio [OR], 3.00; P = 0.0048), male gender (adjusted OR, 3.20; P = 0.0051), and use of castor oil (adjusted OR, 6.29; P = 0.0003) were predictors of capsule excretion within its battery life. Small bowel transit time was shorter and total volume of lavage and fluid intake was lower with castor oil than without (P = 0.0154 and 0.0013, respectively). Overall adequate cleansing level ratios with and without castor oil were 74% and 83%, respectively (P = 0.0713). Per-examinee sensitivity for polyps ≥6 mm with and without castor oil was 83% and 85%, respectively, with specificities of 80% and 78%, respectively. CONCLUSION: Bowel preparation with castor oil was effective for improving capsule excretion rate and reducing liquid loading.

ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry.

Using high-density oligonucleotide microarrays, we investigated DNA copy-number aberrations in cell lines derived from hepatocellular carcinomas (HCCs) and detected a novel amplification at 17p11. To identify the target of amplification at 17p11, we defined the extent of the amplicon and examined HCC cell lines for expression of all seven genes in the 750-kb commonly amplified region. Mitogen-activated protein kinase (MAPK) 7, which encodes extracellular-regulated protein kinase (ERK) 5, was overexpressed in cell lines in which the gene was amplified. An increase in MAPK7 copy number was detected in 35 of 66 primary HCC tumors. Downregulation of MAPK7 by small interfering RNA suppressed the growth of SNU449 cells, the HCC cell line with the greatest amplification and overexpression of MAPK7. ERK5, phosphorylated during the G2/M phases of the cell cycle, regulated entry into mitosis in SNU449 cells. In conclusion, our results suggest that MAPK7 is likely the target of 17p11 amplification and that the ERK5 protein product of MAPK7 promotes the growth of HCC cells by regulating mitotic entry.

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres.

BACKGROUND AND AIM: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis. METHODS: We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 +/- 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group. RESULTS: On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST. CONCLUSIONS: The FSSG score reflects the severity of the endoscopic findings of GERD.

Sildenafil, an inhibitor of phosphodiesterase subtype 5, prevents indomethacin-induced small-intestinal ulceration in rats via a NO/cGMP-dependent mechanism.

We examined the effect of sildenafil, an inhibitor of phosphodiesterase subtype 5, that catalyzes hydrolysis of 3',5'-cyclic guanosine monophosphate (cGMP), on indomethacin-induced small-intestinal ulceration in rats and investigated the mechanism of this action, especially in relation to endogenous nitric oxide (NO). Animals without fasting were given indomethacin (10 mg/kg) s.c. and then killed 24 h later. Indomethacin produced hemorrhagic lesions in the small intestine, accompanied by a promotion of enterobacterial invasion and the expression of inducible NO synthase (iNOS) as well as myeloperoxidase (MPO) activity in the mucosa. Sildenafil (3-20 mg/kg), given p.o. 30 min before indomethacin, dose-dependently reduced the severity of these lesions, with concomitant suppression of the increase in MPO activity, iNOS expression and bacterial invasion. These effects were attenuated by the prior administration of the nonselective NOS inhibitor, N (G)-nitro-L-arginine methyl ester, in an L-arginine-reversible manner. Indomethacin also decreased the secretion of mucus and fluid (enteropooling) and enhanced intestinal motility, but these responses were all prevented by the prior administration of sildenafil. Likewise, pretreatment of the animals with NOR-3, a NO donor, also reversed the functional changes caused by indomethacin, followed by suppression of bacterial invasion and iNOS expression, and prevented the development of intestinal lesions. These results suggest that sildenafil prevents indomethacin-induced small-intestinal ulceration in rats, via a NO/cGMP-dependent mechanism, and this effect is functionally associated with an increase in the secretion of mucus/fluid and a decrease of hypermotility, resulting in the suppression of bacterial invasion and iNOS expression following indomethacin treatment.

MELD score, child-pugh score, and decreased albumin as risk factors for gastric variceal bleeding.

BACKGROUND/AIMS: Ruptured esophagogastric varices are commonly associated with bleeding in patients with portal hypertension. However, the prediction of esophageal variceal bleeding is not matched by means of predicting gastric variceal bleeding. The present study aim is to elucidate risk factors for gastric variceal bleeding. METHODOLOGY: Twelve patients with gastric variceal bleeding and 18 patients receiving preventive treatment for gastric varices were included in the study. RESULTS: The Child-Pugh (8.0 +/- 0.9 vs. 5.5 +/- 0.3; p = 0.0025) and Model for end-stage liver disease (MELD) (10.6 +/- 2.7 vs. 4.0 +/- 0.9; p = 0.0095) scores were significantly higher for patients with bleeding than for those receiving preventive treatment. Serum albumin concentration was significantly lower in bleeding than in preventive treatment cases, as determined by univariate (2.9 +/- 0.2 vs. 3.7 +/- 0.1 mg/dL; p < 0.0001) and multivariate analyses of serological data (odds ratio, 0.02, 95% confidence interval, 0.001-0.479; p = 0.0144). CONCLUSIONS: The Child-Pugh and MELD scores were significantly higher for patients with gastric variceal bleeding than for those receiving preventive treatment, and multivariate analysis revealed that serum albumin was significantly lower in patients with gastric variceal bleeding. Control of serum albumin is important in preventing gastric variceal bleeding.

IL-17 is involved in Helicobacter pylori-induced gastric inflammatory responses in a mouse model.

BACKGROUND: Helicobacter pylori (H. pylori) is the major cause of chronic active gastritis and peptic ulcer disease. Recent studies have shown that H. pylori produces various cytokines that are related to neutrophil or mononuclear cell accumulation. Interleukin-17 (IL-17) is the founding member of an emerging family of inflammatory cytokines whose biological activities remain incompletely defined. In this study, the contributions of IL-17 to the induction of gastric inflammation and to the protection from H. pylori infection were investigated using IL-17 gene-knockout (IL-17(-/-)) mice. MATERIALS AND METHODS: IL-17(-/-)and wild-type C57BL/6 mice were challenged with H. pylori CPY2052 (2 x 10(8) CFU/mL) and the histological and microbiological evaluation were carried out at specified times. IL-17 and myeloperoxidase (MPO) protein levels in tissues were assayed in duplicate using ELISA kits. RESULTS: In wild-type mice, IL-17 was undetected at baseline; however, the protein expression of IL-17 was induced after infection with H. pylori. A severe infiltration of neutrophils appeared in the submucosa and the lamina propria in wild-type mice. In contrast, the degree of neutrophil infiltration in IL-17(-/-) mice was significantly lower than that in wild-type mice. Although wild-type mice infected with H. pylori showed drastically higher MPO activity compared with uninfected wild-type mice, any significant increase in the enzyme activity was not revealed in infected IL-17(-/-) mice. The number of H. pylori colonized in the stomach of IL-17(-/-) mice was significantly lower than that of wild-type mice from 1 to 6 months after infection. CONCLUSIONS: These results suggest that IL-17 may play an important role in the inflammatory response to the H. pylori infection and ultimately influence the outcome of the H. pylori-associated disease.

Dual role of nitric oxide in gastric hypersecretion in the distended stomach: inhibition of acid secretion and stimulation of pepsinongen secretion.

AIMS: We investigate the role of nitric oxide (NO) in the hypersecretion of acid and pepsinogen induced by stomach distension. MAIN METHOD: The rat stomach was distended by instillation of saline through an acute fistula under urethane anesthesia. KEY FINDINGS: Both secretions of acid and pepsinogen were increased by the distension depending on the volume of saline introduced, and responses were attenuated by bilateral cervical vagotomy or prior administration of atropine. N(G)-nitro-l-arginine methyl ester (L-NAME) had a dual effect on these responses, causing an increase in the acid response and a decrease in the pepsin response, both in an l-arginine-sensitive manner. Distension of the stomach increased the luminal NO release; this response was suppressed by vagotomy and L-NAME. Intragastric application of FK409, a NO donor, dose-dependently increased pepsinogen secretion while decreasing acid secretion in the stomach without distension. However, serosal application of both FK409 and 8-bromo-guanosine cyclic 3', 5'-monophosphate (8-Br-cGMP) stimulated the secretion of pepsinogen in isolated mouse stomachs in vitro. The stimulatory effect of FK409 on pepsinogen secretion was totally abolished by LY83583, a guanylate cyclase inhibitor. SIGNIFICANCE: Distension of the stomach increases both acid and pepsinogen secretion through a vagal-cholinergic pathway in addition to the luminal release of NO, and NO affects these responses in opposite ways, suppressing the acid response while enhancing the pepsin response, both mediated by a guanylate cyclase/cGMP pathway.

Clear cell adenocarcinoma of the colon: a case report and review of literature.

A primary clear cell adenocarcinoma of the colon is a rare oncologic entity. We herein report a case of such a tumor of the sigmoid colon in a 71-year-old woman who was successfully treated by an endoscopic polypectomy in our hospital. We also reviewed the published reports regarding cases of primary clear cell tumors in the colon.

Acute pancreatitis from mumps re-infection in adulthood. A case report.

CONTEXT: Acute pancreatitis is a complication of mumps which mainly affects children who then usually acquire permanent immunity. We present the case of a woman with acute pancreatitis caused by mumps re-infection in adulthood. CASE REPORT: A 34-year-old woman developed mild acute pancreatitis caused by re-infection with mumps, as confirmed serologically by enzyme-linked immunosorbent assays mumps-specific IgM and IgG. Acute pancreatitis was indicated by the elevation of amylase and other pancreatic enzymes such as lipase and elastase-1 as well as by swelling of the pancreatic head visualized by abdominal computed tomography. The abdominal symptoms were resolved soon after the administration of a pancreatic enzyme inhibitor. As the swelling of the right and left parotids decreased, serum amylase levels also gradually normalized. CONCLUSION: We believe that this is the first reported case of acute pancreatitis caused by mumps re-infection in an adult. Such re-infection should be considered a possible though rare cause of acute pancreatitis in adulthood.

[A case of adult-onset type II citrullinemia having a liver histology of nonalcoholic steatohepatitis (NASH)].

A 47-year man was hospitalized to our hospital because of consciousness disturbance. He had been abnormally fond of soy bean products since childhood. His plasma levels of ammonia and citrulline were elevated, and we suspected of adult-onset type II citrullinemia (CTLN2). Gene examination demonstrated abnormality in the SLC25A13 gene, confirming CTLN2. Serum levels of hepatobiliary enzymes were increased and his liver biopsy revealed nonalcoholic steatohepatitis. Although we considered that living donor liver transplantation was suitable for the treatment, unfortunately, there was no appropriate donor candidate in his family. He has received conservative treatments, showing a symptom-free course.

ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation.

Array-based comparative genomic hybridization (CGH-array) has a powerful potential for high-throughput identification of genetic aberrations in cell genomes. We identified a homozygous loss of ADAM23 (2q33.3) in the course of a program to screen a panel of gastric cancer (GC) cell lines (1/32, 3.1%) for genomic copy-number aberrations using our custom-made CGH-array. Infrequent homozygous deletion of ADAM23 was also seen in primary gastric tumors (1/39, 2.6%). ADAM23 mRNA was expressed in normal stomach tissue, but not in the majority of GC cell lines without homozygous deletion of this gene. Expression of ADAM23 mRNA was restored to gene-silenced GC cells after treatment with 5-aza 2'-deoxycytidine. The methylation status of the ADAM23 CpG island, which showed promoter activity, correlated inversely with its expression. Methylation of this CpG island was observed both in GC cell lines and in primary GC tissues; in primary tumors with a hypermethylated CpG island, expression of ADAM23 was lower than in adjacent noncancerous tissues. Moreover, restoration of ADAM23 in GC cells reduced their numbers in colony-formation assays. These results suggest that genetic or epigenetic silencing by hypermethylation of the ADAM23 CpG-rich promoter region leads to loss of ADAM23 function, which may be a factor in gastric carcinogenesis.

[A case of pancreatic intraductal papillary-mucinous carcinoma with penetration to the stomach and splenic abscess].

We report the case of an 80-year-old man given a diagnosis of pancreatic intraductal papillary-mucinous carcinoma (IPMC) and early gastric cancer. He refused surgery, therefore endoscopic mucosal resection (EMR) for gastric cancer and careful observation were performed. Penetration of the IPMC to the stomach was observed 3 months later. Ten months after the initial diagnosis, he was found to have a splenic abscess and was subsequently treated by antibiotics and percutaneous drainage, and a fistula between the IPMC and the splenic abscess was observed. We suppose IPMC penetration to the spleen and bacterial transmission from the stomach through the fistula caused the splenic abscess. While IPMC is recognized as a low-grade malignancy, some cases of invasive carcinoma with fistulation to adjacent organs have been reported. To the best of our knowledge, this is the first case of IPMC associated with splenic abscess due to pancreatosplenic fistula.

[A case of minimal invasive carcinoma from intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas].

A 69-year-old man was referred to our hospital for epigastralgia. He was found to have elevation of serum amylase and CA19-9. Ultrasonography, abdominal CT, MRCP, ERCP and EUS showed the cystic lesion and a possibility of an other tumor. There was a stenosis of the main pancreatic duct (MPD) at the pancreas head and dilatation of the MPD from the body to the tail. Intraductal papillary mucinous neoplasm (IPMN) of the branch pancreatic duct was diagnosed, and there was a likelihood of ductal carcinoma of the pancreas. We therefore performed pancreatoduodenectomy. Pathological finding showed invasive carcinoma from an intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas.

Endoscopic resection for the diagnosis of visceral Kaposi's sarcoma.

Kaposi's sarcoma is an uncommon neoplasm that occasionally involves the gastrointestinal tract in immunosuppressed individuals. Infection with human herpes virus 8 is known to be necessary for developing all forms of Kaposi's sarcoma. We report a renal transplant recipient who developed visceral Kaposi's sarcoma 18 months after the transplantation. In Oriental countries, the incidence of Kaposi's sarcoma is extremely low, and this is the first case of Kaposi's sarcoma arising from a transplant recipient in Japan. Standard forceps biopsies of the gastric lesions failed to make the correct diagnosis. However, endoscopic resection successfully led to the correct diagnosis of Kaposi's sarcoma and herpes simplex virus 8 infection as well. This is the first report of a patient with visceral Kaposi's sarcoma who underwent endoscopic resection that reliably confirmed histological diagnosis and the viral genome at the same time.

Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy.

AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosa-associated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy. METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy, the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissue-fluorescence in situ hybridization (FISH), using chromosome-specific alpha-satellite DNA probes for chromosomes 3,7,12, and 18 and YAC clones for t(11;18)(q21;q21). RESULTS: Seven of the 13 patients had complete regression (CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients. CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

Small bowel non-Hodgkin's lymphoma remaining in complete remission by surgical resection and adjuvant rituximab therapy.

A 44-year-old man was referred to our hospital with intermittent abdominal pain. Because distention of fluid- and gas-filled loops of small intestine was proved by X-ray, the patient was diagnosed as having small bowel obstruction. A laparotomy revealed a segmental stenosis in the jejunum, which showed diffuse thickening of the intestinal wall. Some mesenteric lymph nodes were swollen. Pathological examination was defined. We diagnosed diffuse large B-cell lymphoma based on the pathological findings of diffuse transmural infiltration of large lymphoid cells and flow-cytometric analyses. Rituximab was administered as adjuvant therapy at weekly doses of 375 mg/m2. Four cycles were performed every 6 mo and he remained CR. Rituximab may be effective as adjuvant therapy.

Recurrent chromosomal rearrangements at bands 8q24 and 11q13 in gastric cancer as detected by multicolor spectral karyotyping.

AIM: To identify chromosomal translocations specific to gastric cancer (GC), spectral karyotyping (SKY) analysis was performed on established cell lines and cancerous ascitic fluids. METHODS: SKY analysis of 10 established cell lines and seven cancerous ascitic fluid samples identified recurrent chromosomal breakpoints and translocations in GC, several of which involved chromosomal loci of oncogenes or tumor suppressor genes. RESULTS: A total of 630 chromosomal breaks were identified. Chromosome no.8 was the most frequently involved in rearrangements (65 breaks), followed by chromosomes no.11 (53), no. 1 (49), no. 7 (46), no. 13 (37), no. 3 (36), no. 17 (33), and no. 20 (29). Frequent breakpoints were detected in 8q24.1 (30 breaks), 11q13 (29), 13q14 (16), 20q11.2 (14), 7q32 (13), 17q11.2 (13), 18q21 (12), 17q23 (9), 18q11.2 (9). SKY analysis identified a total of 242 chromosomal rearrangements including 190 reciprocal and non-reciprocal translocations. The recurrent combinations of chromosomal bands involved in translocations were 8q24.1 and 13q14 (3 cases), 8q24.1 and 11q13 (3), 11q13 and 17q11.2 (2), and 18q11.2 and 20q11.2 (2). Our study validated the ability of SKY to characterize in detail the chromosomal rearrangements in solid tumors and derived cell lines. Moreover, fluorescence in situ hybridization helped to identify the insertions, translocations, and homogeneously staining regions of MYC and CCND1 gene loci. CONCLUSION: The non-random co-localization of certain cytogenetic bands suggests the importance of chromosomal translocations in gastric carcinogenesis, by serving as landmarks for the cloning of GC causing genes.

Overexpression of CD10 and reduced MUC2 expression correlate with the development and progression of colorectal neoplasms.

There are two opposing theories of the natural history of colorectal neoplasm, adenoma-carcinoma sequence and de novo carcinogenesis. To elucidate the histogenesis of colorectal carcinoma, we investigated the expression of CD10, MUC2, MUC5AC, MUC6, and p53 in colorectal neoplasms. Sixty-seven morphologically distinct neoplastic specimens were divided into the following groups according to morphology: adenoma (groups A and B), protruded-type carcinoma (group C), superficial-type carcinoma with adenomatous component (group D), or superficial-type carcinomas without any adenomatous component (group E). Diagnoses of adenomas and carcinomas were based upon the Vienna classification of gastrointestinal epithelial neoplasia. The expression of CD10 in group E lesions was more intense than in the other groups. Regardless of morphology, MUC2 expression was significantly decreased in CD10-positive carcinomas, and the p53-positive rate was much higher in CD10-positive than in CD10-negative carcinomas. The overexpression of CD10 and reduced expression of MUC2 may be associated with the development and progression of colorectal carcinoma. A specific tendency was evident in superficial-type carcinomas without any adenomatous component (de novo carcinomas). These carcinomas are considered to be more aggressive than other morphologically distinct carcinomas.

[A case report of esophageal cancer with tracheoesophageal fistula--improving the quality of life by using a covered self-expandable metallic stent].

We present the case of a 64-year-old male who was diagnosed with esophageal cancer with tracheal invasion and distant lymph node metastases, and he received chemoradiation therapy. The therapy resulted in complete remission. However, he was unable to eat anything because of missed swallowing caused by a large tracheoesophageal fistula. The placement of a covered self-expandable metallic stent (SEMS) improved his quality of life and palliated dysphagia for 3 months. Stenting in the cervical or upper esophagus may cause discomfort. However, the placement of a covered SEMS is one of the useful palliative treatments for esophageal cancer with tracheoesophageal fistula.

Effects of etodolac, a selective cyclooxygenase-2 inhibitor, on the expression of E-cadherin-catenin complexes in gastrointestinal cell lines.

BACKGROUND: Recent studies have shown that cyclooxygenase-2 (COX-2) inhibitors may participate in the proliferation of cancer cells. Because the cadherin-catenin complex is not only a key component of the adherens junction but also has been suggested to regulate cell proliferation, modulation of these molecules may be a mechanism by which COX-2 activity affects cell proliferation. In this study, we evaluated the effect of a COX-2 inhibitor on the proliferation and expression of E-cadherin-complexes in gastrointestinal cancer cell lines. METHODS: The gastrointestinal cancer cell lines Caco2, HT29, and MKN45 were grown for 24 h in the presence and absence of a selective COX-2 inhibitor, etodolac (10(-5), 10(-4), and 10(-3) M). Cell proliferation was assessed by (3)H-thymidine incorporation, and the expression of E-cadherin and catenins was assessed by Western blotting, Northern blotting, and immunofluorescence. RESULTS: Etodolac induced a significant reduction in cell proliferation in Caco2 and MKN45 cells. E-cadherin expression was upregulated after stimulation with etodolac in Caco2 cells, whereas the expression of alpha-, beta-, gamma- and p120-catenins was not modified. The expression of E-cadherin mRNA was also upregulated in Caco2 cells, and was upregulated also in MKN45 cells, which did not express normal E-cadherin protein by the use of a mouse monoclonal antibody against human E-cadherin, HECD-1 antibody. Immunofluorescence revealed that the increased E-cadherin was localized at the cytoplasmic membrane. CONCLUSIONS: The inhibition of cell growth by etodolac in Caco-2 cells was associated with a dose-dependent upregulation and intense cytoplasmic localization of E-cadherin. No quantitative change in catenin expression was found in this phenomenon. These findings suggest that the COX-2 inhibitor affects the transcription of E-cadherin, or that there may be some homeostatic link between the cell cycle and E-cadherin transcription.