Endoscopic observation of Meckel's diverticulum by double balloon endoscopy: report of five cases.

BACKGROUND AND AIM: Most cases of Meckel's diverticula are asymptomatic, however, some cases presented with gastrointestinal (GI) bleeding. It is often difficult to determine whether Meckel's diverticulum is a source of obscure GI bleeding. Double balloon endoscopy allows endoscopic access to the entire small intestine. The aim of this study was to compare endoscopic findings of three hemorrhagic and two non-hemorrhagic Meckel's diverticula in patients with obscure GI bleeding using this novel technique. METHODS: Between September 2000 and April 2005, 354 enteroscopies, including 162 anterograde and 192 retrograde procedures, were performed on 217 patients at the Jichi Medical University Hospital, Japan, using the double balloon endoscopy system. Five consecutive patients where Meckel's diverticulum was endoscopically observed were selected and analyzed. RESULTS: Double balloon endoscopy enabled direct observation of Meckel's diverticula in all five patients. Surgical procedures were indicated for three patients where double balloon endoscopy discovered ulcers. By contrast, double balloon endoscopy detected other sources of bleeding in the remaining two patients where no ulcers were found in the Meckel's diverticula. CONCLUSION: Endoscopic observation of the ulcers in Meckel's diverticula was important evidence of bleeding in patients with obscure GI bleeding. Other sources of bleeding should be considered when no ulcers are found in the Meckel's diverticula.

Endoscopic classification of vascular lesions of the small intestine (with videos).

BACKGROUND: Small-intestinal vascular lesions observed by endoscopy vary in appearance. Angioectasia is a venous lesion that requires cauterization; a Dieulafoy's lesion and arteriovenous malformation may cause arterial bleeding, which requires clipping or laparotomy. For selection of the appropriate treatment, it is necessary to distinguish between venous and arterial lesions. PATIENTS AND METHODS: We classified these lesions into the following 6 groups: type 1a, punctulate erythema (< 1 mm), with or without oozing; type 1b, patchy erythema (a few mm), with or without oozing; type 2a, punctulate lesions (< 1 mm), with pulsatile bleeding; type 2b, pulsatile red protrusion, without surrounding venous dilatation; type 3, pulsatile red protrusion, with surrounding venous dilatation; type 4, other lesions not classified into any of the above categories. Types 1a and 1b are considered angioectasias. Types 2a and 2b are Dieulafoy's lesions. Type 3 represents an arteriovenous malformation. Type 4 is unclassifiable. Three endoscopists independently reviewed images and video to classify 102 vascular lesions into the above types. The rate of concordance among the 3 endoscopists was calculated. RESULTS: Eighty-four lesions (82%) were classified into the same type by all of 3 endoscopists. The mean kappa value (standard deviation) for the concordance was 0.72 +/- 0.07, which confirmed substantial interobserver concordance. LIMITATIONS: This classification is applicable only to endoscopic findings. It was desirable to correlate the histopathologic findings with endoscopic observations. CONCLUSIONS: This classification will be useful for selecting the hemostatic procedure and outcome studies.

[Diagnosis and treatment using double balloon endoscopy].

Double balloon endoscopy (DBE) and video capsule endoscopy (VCE) are breakthrough methods for endoscopic examination of the small intestine. Using these modalities, it has been clarified that use of nonsteroidal anti-inflammatory drugs (NSAIDs) induces ulcers not only in upper gastrointestinal tract but also in the small intestine. Furthermore, concentric membranous strictures, so called "diaphragm disease" can be induced with long-term NSAID use in some cases. The best therapy for ulcers induced by NSAIDs in small intestine is cessation of NSAIDs use so far. For these diaphragm-like small intestinal strictures, a balloon dilation therapy using DBE can be performed safety and effectively.

Non-steroidal anti-inflammatory drug-induced small bowel injuries identified by double-balloon endoscopy.

AIM: To clarify clinical features of the NSAID-induced small bowel lesions using a new method of endoscopy. METHODS: This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone double-balloon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at Jichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient. RESULTS: Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively. The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug. CONCLUSION: NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon.

beta-Catenin splice variants and downstream targets as markers for neoplastic progression of esophageal cancer.

This study characterizes the frequency of exon 3 CTNNB1 mutations and compares the expression of CTNNB1 transcript variants and downstream targets MYC and WAF1 (p21) across the neoplastic progression of esophageal squamous cell carcinomas (ESCCs). Mutational analysis was performed on 56 tumors and corresponding germline DNA, using primers to exon 3 of CTNNB1 and SSCP DNA sequencing gels. Quantitative Real Time RT-PCR was performed on 45 foci representing the histological spectrum from normal to invasive cancer, using specific primer sets for alternative splice variants that differ by the presence (16A) or absence (16B) of a 159-bp noncoding segment of exon 16 of CTNNB1, in conjunction with downstream targets MYC and WAF1. Two unique mutations were identified, S37F in the SxxxS repeat region, and a germline polymorphism, T59A. Thus, mutation of CTNNB1 exon 3 is a rare event in this population. RT-PCR analysis successfully confirmed the presence of both beta-catenin splice variants in histologically normal and preneoplastic squamous epithelium, and invasive tumors of the esophagus, and identified a significant reduction in the 16A/16B ratio (P = 0.014) and an accompanying significant increase in the MYC/WAF1 expression ratio (P = 0.001) with progression from normal mucosa to dysplasia. This represents the first identification of two CTNNB1 transcripts in histologically "normal" esophageal squamous cells, squamous dysplasia, and invasive ESCC. These results show an increase in the minor mRNA (16B) isoform and changes in the expression of downstream markers consistent with increased transcription during the histological progression from normal to squamous dysplasia.

Technical modification of the double-balloon endoscopy to access to the proximal side of the stenosis in the distal colon.

BACKGROUND: The inability to pass endoscopes beyond strictures is a considerable problem in patients with a colonic stricture. METHODS: In patients with bowel obstruction, we have modified the insertion method for double-balloon endoscopy with a long, transnasal decompression tube. OBSERVATIONS: We have succeeded in reaching the proximal side of the stricture from the oral approach across the entire small bowel in a patient. CONCLUSIONS: This modified double-balloon enteroscopy is useful for patients with bowel obstruction in whom a long decompression tube is already placed.

Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine.

AIM: To evaluate the clinical outcome of enteroscopy, using the double-balloon method, focusing on the involvement of neoplasms in strictures of the small intestine. METHODS: Enteroscopy, using the double-balloon method, was performed between December 1999 and December 2002 at Jichi Medical School Hospital, Japan and strictures of the small intestine were found in 17 out of 62 patients. These 17 consecutive patients were subjected to analysis. RESULTS: The double-balloon enteroscopy contributed to the diagnosis of small intestinal neoplasms found in 3 out of 17 patients by direct observation of the strictures as well as biopsy sampling. Surgical procedures were chosen for these three patients, while balloon dilation was chosen for the strictures in four patients diagnosed with inflammation without involvement of neoplasm. CONCLUSION: Double-balloon enteroscopy is a useful method for the diagnosis and treatment of strictures in the small bowel.

Nuclear accumulation of beta-catenin occurs commonly in the epithelial cells of juvenile polyps.

In the two conditions juvenile polyps (JPs) and juvenile polyposis coli (JPC), colonic polyps may have overlapping histologic and phenotypic appearance, but JPC confers a significant risk for colon adenocarcinoma. Although not thought to contain adenomatous polyposis coli (APC) mutations, the status of beta-catenin and full-length APC protein expression in JPs is not known. We evaluated beta-catenin and full-length APC protein expression in JPs from children with JPs and JPC. Cases were identified through endoscopic procedure records. Immunohistochemistry was performed for beta-catenin and full-length APC protein. Loss of heterozygosity at the APC gene locus on chromosome 5 was assessed using two APC-linked microsatellite markers. Polyp and normal colonic tissue were analyzed from 36 children with JPs and 9 with JPC. Both APC and beta-catenin immunoreactivity were present in epithelial cells from all samples but in different patterns. In all normal colon and polyp samples, APC expression was cytoplasmic with maximal immunoreactivity in the goblet cells. In contrast, beta-catenin immunoreactivity in epithelial cells was limited to the plasma membrane in normal colon but was both cytoplasmic and nuclear in all 45 JPs. No evidence of APC gene loss of heterozygosity was found. In polyps from children with JPs and JPC, nuclear beta-catenin accumulation is a consistent feature, and it is not due to APC gene mutation or loss of full-length APC protein expression. Thus, beta-catenin accumulation may be intrinsic to the formation of juvenile-type polyps through an as-yet-undefined mechanism.

Gastrointestinal stromal tumor in the jejunum: diagnosis and control of bleeding with electrocoagulation by using double-balloon enteroscopy.

A 43-year-old man presented with gastrointestinal bleeding. A tumor with central ulceration was observed in the jejunum, with the use of a new enteroscopy system called "double-balloon enteroscopy". Bleeding after biopsy sampling of the tumor was controlled endoscopically by using electrocoagulation. Histological findings of the biopsy specimens were consistent with gastrointestinal stromal tumor, and this was surgically resected. Double-balloon enteroscopy was useful for the diagnosis as well as the control of bleeding in this patient.

Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases.

BACKGROUND & AIMS: A specialized system for a new method for enteroscopy, the double-balloon method, was developed. The aim of this study was to evaluate the usefulness of this endoscopic system for small-intestinal disorders. METHODS: The double-balloon endoscopy system was used to perform 178 enteroscopies (89 by the anterograde approach and 89 by the retrograde approach) in 123 patients. The system was assessed on the basis of the rates of success in jejunal and ileal insertion and the entire examination of the small intestine, diagnostic yields, ability to perform treatment, and complications. RESULTS: Insertion of the endoscope beyond the ligament of Treitz or ileocecal valve was possible in all 178 procedures. It was possible to observe approximately one half to two thirds of the entire small intestine by each approach, and observation of the entire small intestine was possible in 24 (86%) of 28 trials. The source of bleeding was identified in 50 (76%) of 66 patients with GI bleeding, scrutiny of strictures was possible in 23 patients, and a tumor was examined endoscopically in 17 patients. Two complications (1.1%) occurred. Endoscopic therapies in the small intestine including hemostasis (12 cases), polypectomy (1 case), endoscopic mucosal resection (1 case), balloon dilation (6 cases), and stent placement (2 cases) were performed successfully. CONCLUSIONS: Double-balloon endoscopy permits the exploration of the small intestine with a high success rate of total enteroscopy. The procedure is safe and useful, and it provides high diagnostic yields and therapeutic capabilities.

Direct observation with double-balloon enteroscopy of an intestinal intramural hematoma resulting in anticoagulant ileus.

In the case presented here, we have succeeded in describing the endoscopic findings of anticoagulant ileus and evaluated the degree of bleeding as well as ischemia through endoscopic observation. We have demonstrated that enteroscopy using the double-balloon method is a useful diagnostic tool in the evaluation of a patient suspected to have anticoagulant ileus.

Her-2/neu expression and gene amplification in gastrinomas: correlations with tumor biology, growth, and aggressiveness.

A proportion of gastrointestinal neuroendocrine tumors are aggressive; however, little is known of molecular determinants of their growth, and molecular studies have identified no useful prognostic factors. Overexpression of HER-2/neu is common in some nonendocrine tumors, frequently correlates with increased tumor aggressiveness, and can be used as a basis of treatment with trastuzumab. Little is known of its expression in malignant pancreatic endocrine tumors. In the present study HER-2/neu gene amplification and expression was determined in 43 gastrinomas from different patients. Results were correlated with clinical, laboratory, and tumor characteristics including tumor growth. HER-2/neu gene amplification was assessed by differential PCR, mRNA levels assessed by quantitative PCR, and protein by immunohistochemistry. Fourteen percent of patients had HER-2/neu gene amplification in tumors compared with levels in their WBCs. HER-2/neu mRNA varied over a 700-fold range. However, only 3% exceeded levels seen in normal pancreas, and immunohistochemistry did not show protein overexpression in any tumor (n = 10). HER-2/neu mRNA levels were significantly higher (P = 0.032) in tumors associated with liver metastases but not with tumor location or size. These results show that HER-2/neu amplification/overexpression does not seem to play a role in the molecular pathogenesis of most gastrinomas, as suggested in a previous study involving small numbers of cases. However, mild gene amplification occurs in a subset, and overexpression is associated with aggressiveness. Therefore, HER-2/neu levels could have prognostic significance as well as identify a patient subset with gastrinomas who might benefit from trastuzumab treatment.

Overexpression of epidermal growth factor and hepatocyte growth factor receptors in a proportion of gastrinomas correlates with aggressive growth and lower curability.

PURPOSE: Growth factor receptor expression and activation, particularly for epidermal growth factor (EGF) and hepatocyte growth factor (HGF), in many endocrine and nonendocrine tumors is important in determining tumor recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear. EXPERIMENTAL DESIGN: To address this question, we analyzed the extent of EGFR and HGFR expression in gastrinomas from 38 patients with Zollinger-Ellison syndrome and correlated it with clinical and tumor characteristics. EGFR (n = 38) and HGFR (n = 22) mRNA levels were determined by competitive PCR, and immunohistochemistry was performed on a subset. RESULTS: In each of the gastrinomas studied, detectable levels of EGFR and HGFR mRNA were present. Low levels of EGFR protein expression were detected in 40% of gastrinomas and HGFR protein expression in 90%. EGFR mRNA expression varied by 1050-fold and HGFR by 375-fold. Eighteen percent of gastrinomas overexpressed EGFR mRNA and 14% overexpressed HGFR mRNA, compared with normal pancreas. Maximal EGFR and HGFR mRNA levels were 4- and 1.2-fold increased and correlated with the presence of liver metastases (P = 0.034) and decreased long-term curability (P = 0.027) but not tumor location, size, or tumor functional characteristics. CONCLUSIONS: These above results indicate that EGFR and HGFR mRNA are universally expressed in gastrinomas. Furthermore, each is overexpressed in a minority (15-20%) of the gastrinomas, and the overexpression correlates with aggressive growth and lower curability.