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.

Novel findings of capsule endoscopy and double-balloon enteroscopy in a case of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis is a rare disease with unknown cause. It is characterized by marked eosinophilic infiltration in the gastrointestinal tract. There are few reports that include detailed endoscopic findings of eosinophilic gastroenteritis in the small intestine. A 48-year-old man complaining of abdominal pain was admitted to our hospital. A complete blood count showed eosinophilia, and ascites showed eosinophilia. Abdominal computed tomography indicated dilation, wall thickening of the small intestine, and ascites. Capsule endoscopy revealed stenosis, dilation, edematous mucosa, and aperistalsis in the upper jejunum, together with circumferential ulcerated lesions and ulcer scars in the ileum. Double-balloon enteroscopy revealed a 10-cm segmental mucosal edema and stenosis in the ileum. In one segment, there were several circumferential ulcerated lesions. These lesions included both small round ulcers and large ulcers with redness and mucosal edema. Histological examination revealed infiltration of eosinophils into biopsy specimens of the ileum. The patient was diagnosed with eosinophilic gastroenteritis. The patient recovered after rehydration therapy. After 9 months, capsule endoscopy revealed no ulcers or edema. In this report, we describe the findings of capsule endoscopy and double-balloon enteroscopy in a case of eosinophilic gastroenteritis.

Tissue factor pathway inhibitor 2 (TFPI2) is frequently silenced by aberrant promoter hypermethylation in gastric cancer.

Aberrant methylation of promoter CpG islands is associated with transcriptional inactivation of tumor-suppressor genes in cancer. TFPI2, a Kunitz-type serine proteinase inhibitor, has been identified as a putative tumor-suppressor gene from genome-wide screening for aberrant methylation, using a microarray combined with the methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dCyd) in various types of tumors. We assessed the methylation status of TFPI2 and investigated its expression pattern in human primary gastric cancer (GC) tissues and in GC cell lines. Hypermethylation of the promoter CpG island, which was observed in more or less all of GC cell lines, was prevalent in a high proportion of primary GC tissues (15/18, or 83%), compared with noncancerous (4/18, or 22%) or normal (0/3, or 0%) stomach tissues, and expression of TFPI2 mRNA was reduced in 7 of the 17 primary GC tissues (41%). Moreover, immunohistochemical analyses showed decreased levels of TFPI-2 protein, compared with adjacent noncancerous tissues in 8 of the 20 primary GC tissues examined (40%). TFPI2 mRNA expression was restored in gene-silenced GC cells after treatment with 5-aza-dCyd. Aberrant methylation of TFPI2 promoter CpG island occurred not only in GC cells but also in primary GC tissues at a high frequency, suggesting that epigenetic silencing of TFPI2 may contribute to gastric carcinogenesis.

Epigenetic silencing of RELN in gastric cancer.

RELN (Reelin) is an extracellular glycoprotein that plays a critical role in neuronal migration. Here we show that the RELN gene is frequently silenced in gastric cancers (GCs) by aberrant promoter hypermethylation. Although RELN was strongly expressed in non-tumor gastric epithelia, its expression was weak, or absent, in GC cell lines and primary GC tumors. Absence of RELN expression significantly correlated with a more advanced stage of GC. Methylation of the RELN promoter was frequently found in GC cell lines and in primary GC tumors. These findings suggest that disruption of the RELN pathway may be involved in gastric carcinogenesis.

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.

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.

Clostridium difficile-associated diarrhea with hematochezia is associated with ulcer formation.

OBJECTIVE: Clostridium difficile-associated diarrhea (CDAD) is a well-known iatrogenic infection with typical endoscopic features including pseudomembranes and intervening normal mucosa. Clinically, diarrhea frequently occurs, but occurrence of hematochezia is rare. The objective of this study was to investigate the background and endoscopic features of CDAD patients with hematochezia. MATERIAL AND METHODS: The endoscopic and clinical findings in 12 patients who showed evidence of C. difficile toxin A and who underwent colonoscopy between April 2002 and July 2007 were investigated retrospectively. RESULTS: Eight patients were diagnosed as having CDAD and 4 patients had a diagnosis of ulcerative colitis. Six of the patients with CDAD presented with hematochezia, and 4 of them were diagnosed with hematological malignancies and received anticancer chemotherapy. Colonic ulcer was demonstrated in all CDAD patients with hematochezia, and bleeding from the ulcer was endoscopically confirmed in all of them. CONCLUSIONS: CDAD accompanied by hematochezia is closely associated with ulcer formation. Ulcers are thought to occur during recovery from nadir after anticancer treatment, and white blood cells appear to be essential for their formation. Physicians should therefore pay close attention to the occurrence of colonic ulcer, especially in patients with CDAD during recovery from nadir.

Levels of interleukin-18 are markedly increased in Helicobacter pylori-infected gastric mucosa among patients with specific IL18 genotypes.

BACKGROUND: The cellular immune response in gastric mucosa infected with Helicobacter pylori is proposed to be predominantly of the T helper cell type 1 type. METHODS: Interleukin (IL)-18, IL-12, and interferon (IFN)-gamma levels were measured in gastric mucosal biopsy specimens by reverse-transcription polymerase chain reaction (PCR) and by enzyme-linked immunosorbent assay; IL18 polymorphisms were determined by PCR. RESULTS: Biopsy specimens from 128 patients (56 with nonulcer dyspepsia, 28 with gastric ulcers, 28 with duodenal ulcers, and 16 with gastric cancer) were examined; 96 patients had H. pylori infection. IL-18 levels were markedly up-regulated in mucosa infected with H. pylori (P < .001), whereas IL-12 and IFN-gamma levels were independent of H. pylori status. IL-18 levels correlated with IFN-gamma levels only in infected patients (R = 0.31 to R = 0.51). IL-18 levels were the determining factor for monocyte infiltration in H. pylori-infected mucosa (P < .001). H. pylori-infected patients displaying IL18 -607C/C and -137G/G had higher IL-18 levels than did those with other genotypes and were more likely to experience treatment failure. CONCLUSION: H. pylori infection induces IL-18 in the gastric mucosa. H. pylori-infected patients with IL18 -607C/C and -137G/G have higher IL-18 levels, which causes severe gastric inflammation. IL18 genotype might be a marker for predicting the effects of eradication therapy.

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.

[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.

Pseudomyxoma peritonei occurring after an uneventful 23 years interval from appendectomy.

A 77-year-old male was admitted to our hospital for a bulky abdominal mass. He had a history of appendectomy under the diagnosis of appendiceal rupture 23 years previously. He also had received a radical lung resection for an early lung cancer 2 years earlier in another hospital. Tentative diagnosis of peritoneal metastases from the lung cancer was made. He then received 3 courses of chemotherapy, but failed to reach a remission. The final diagnosis of pseudomyxoma peritonei was made by means of abdominocentesis, and he underwent debulking surgery. However, he died on day 56 after the surgery. Pseudomyxoma peritonei requires careful observation, as it has the possibility to be detected after a long-term follow-up period of more than 20 years.

Comparison of clinical features and patient background in functional dyspepsia and peptic ulcer.

To elucidate the clinical features of functional dyspepsia (FD), patients with FD were compared with patients with peptic ulcer. Fifty-eight FD and fifty-nine peptic ulcer patients were compared with respect to clinical features and patient background. In the FD group, symptoms of dyspepsia, especially upper abdominal fullness and nausea, were more common than in the peptic ulcer group. The FD group complained greater distress (severity of the most distressing symptom; P < .001) and showed higher State-Trait Anxiety Inventory (STAI) scores (trait-anxiety score; P < .05). A higher proportion of FD patients had consulted another physician (P < .01). Even when subjects from the FD and peptic ulcer group in this study were matched for age and gender and compared with respect to these variables, almost the same characteristics were seen. These results indicate that FD markedly decreases quality of life in a variety of aspects.

[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.

[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.

Cytogenetic and clinicopathological characterization by fluorescence in situ hybridization on paraffin-embedded tissue sections of twenty-six cases with malignant lymphoma of small intestine.

OBJECTIVE: In small intestinal malignant lymphoma (SIML), the correlation between specific chromosomal abnormalities and clinicopathological features remains unclear. The aim of this study was to determine the frequency of chromosomal translocations involving the BCL1, BCL2, c-MYC, BCL6 and MALT1 genes by using fluorescence in situ hybridization directly on paraffin-embedded tissue sections (tissue-FISH). MATERIAL AND METHODS: Twenty-six cases diagnosed as having SIML between 1996 and 2003 were the subjects of the clinicopathological investigation conducted in this study. Tissue-FISH was performed with specific probes on paraffin-embedded tissue sections as described previously. RESULTS: The primary site was frequently located at the duodenum (9 cases, 35%). In accordance with the World Health Organization classification, 14 (53%) cases were diagnosed as having diffuse large B-cell lymphoma (DLBCL) and 6 (23%) as marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Macroscopically, DLBCL and MALT lymphoma displayed various macroscopic features. Cytogenetically, IGH-BCL2 translocation was detected in 3 (21%) out of 14 DLBCL cases, but in none of the MALT lymphomas. BCL6 translocation was detected in 5 (35%) of 14 DLBCL cases and in 1 (17%) of 6 MALT lymphoma cases (17%). API2-MALT1 translocation was detected in 1 (7%) of 14 DLBCL cases and in 1 (17%) of 6 MALT lymphoma cases. CONCLUSIONS: The duodenum was preferentially involved in SIML. DLBCL and MALT lymphoma showed various macroscopic features. Tissue-FISH analysis disclosed that DLBCL is cytogenetically heterogeneous. Furthermore, our study validated tissue-FISH as an additional promising diagnostic tool for detecting specific chromosomal translocations in NHL.

Clinicopathological characteristics of esophageal squamous papillomas in Japanese patients--with comparison of findings from Western countries.

To clarify the characteristics of esophageal squamous papillomas (ESPs) in the Japanese population, we investigated 38 ESPs of 35 Japanese patients from a file with 17,387 upper gastrointestinal endoscopies in our university hospital. ESPs accounted for 0.20% of the total number of endoscopies and comprised 21 females and 14 males with an average age of 59.2 years. More than half of the ESPs (52.6%) were located in the middle esophagus. The ratio of human papilloma virus (HPV) positive ESPs was 10.5% and all were located in the middle esophagus of female patients only. HPV-positive ESP cases were younger (46.8 years) than HPV-negative cases (60.8 years). Based on comparison with the reports from western countries, we attribute the low prevalence in the lower esophagus to the relatively fewer occurrences of severe reflux esophagitis (RE) due to chronic gastritis with low gastric acid secretion among Japanese patients.

[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.

Expression of cytokeratins 7 and 20 in serrated adenoma and related diseases.

The entity of serrated adenoma of the colorectum was first proposed in 1990, and it was characterized as epithelial neoplasia combining the architectural features of a hyperplastic polyp with the cytological features of an adenoma. Over the past few years, various clinicopathological studies on serrated adenoma have been reported, but its histogenesis remains unclear. Recently the existence of a "serrated neoplasia pathway" leading to malignancy, which is different from the so-called adenoma-carcinoma sequence, has been discussed. Yao et al. reported that hyperplastic polyps and serrated adenomas share a common cell lineage with gastric differentiation. To clarify the existence of the serrated neoplasia pathway, we performed immunohistochemical staining of cytokeratin 7 (CK7) and cytokeratin 20 (CK20), which are commonly used to determine the primary site of a metastatic lesion, and we examined the pattern of CK7/CK20 expression in various colorectal lesions including 44 serrated adenomas, 25 hyperplastic polyps, 20 traditional adenomas, and 48 carcinomas. An obvious difference existed in the pattern of CK7/CK20 expression between the serrated lesions (hyperplastic polyps and serrated adenomas) and others. The majority of serrated adenomas and hyperplastic polyps presented a CK7+/CK20+ pattern, whereas most conventional adenomas and adenocarcinomas expressed CK7-/CK20+. Adenocarcinoma developing in serrated adenoma also presented a CK7+/CK20+ pattern. There are several reports that CK7 is a possible marker of transient dedifferentiation in the gastric carcinogenesis process. Taken together with the present results, a distinct pathway of colorectal carcinogenesis must exist, which is different from the adenoma-carcinoma sequence. CK7 is a possible marker for the serrated neoplasia pathway of colorectal carcinogenesis.