Measurement of intragastric pressure: an objective method to ascertain whether gastric wall extension is sufficient for assessment of the non-extension sign.

Background and study aims The optimal intragastric pressure (IP) for strong gastric wall extension is unclear. We aimed to develop an accurate method to measure IP using endoscopy and determine the pressure required for strong gastric wall extension. Methods An in vitro experiment using an endoscope with a rubber attached at its tip was conducted. The process of inserting the pressure measurement probe into the forceps channel was skipped, and the tube of the pressure measurement device was directly connected to the forceps channel. In vivo, the pressure in 51 consecutive patients at the time of strong gastric wall extension was measured. Strong extension of the gastric wall was defined as when the folds in the greater curvature were flattened as a result of sufficient extension of the gastric wall by insufflated air during upper gastrointestinal endoscopy. The IP at that time was measured. Results In vitr o , 20 mL of tap water was injected once into the forceps channel and then aspirated for 10 seconds. Pressure measurement after irrigation of the forceps channel as well as the measurement by inserting the probe procedure were accurately performed. In vivo, among the 51 included patients, the mean IP (range) was 14.7 mmHg (10-23). Strong extension of the gastric wall was obtained in 96.1 % of patients when the IP was 20 mmHg. Conclusions We developed an accurate method to measure IP using upper gastrointestinal endoscopy. Strong extension of the gastric wall was obtained in almost all patients when the IP was 20 mmHg.

Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations.

BACKGROUND: We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2A1 gene (CEAS). Crohn's disease (CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from CD. AIM: To examine whether prostaglandin E major urinary metabolites (PGE-MUM) can serve as a biomarker to distinguish CEAS from CD. METHODS: This was a transactional study of 20 patients with CEAS and 98 patients with CD. CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2A1. We measured the concentration of PGE-MUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic (ROC) curve analysis. RESULTS: Twenty Japanese patients with CEAS and 98 patients with CD were enrolled. PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD (median 102.7 vs 27.9 µg/g × Cre, P < 0.0001). One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS [95% confidence interval (CI) 3.2-16.7]. A logistic regression analysis revealed that the association was significant even after adjusting confounding factors (adjusted odds ratio 29.6, 95%CI 4.7-185.7). ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9 µg/g × Cre with 95.0% sensitivity and 79.6% specificity. CONCLUSION: PGE-MUM measurement is a convenient, non-invasive and useful test for the distinction of CEAS from CD.

Crohn's disease-specific mortality: a 30-year cohort study at a tertiary referral center in Japan.

BACKGROUND: In this study, survival and cause of death were investigated in patients with Crohn's disease (CD) at a tertiary referral center. METHODS: A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000. RESULTS: The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7; 95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis. CONCLUSION: The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs.

Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn's disease.

BACKGROUND: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a hereditary disease caused by mutations in the SLCO2A1 gene and characterized by multiple small intestinal ulcers of nonspecific histology. SLCO2A1 is also a causal gene of primary hypertrophic osteoarthropathy (PHO). However, little is known about the clinical features of CEAS or PHO. METHODS: Sixty-five Japanese patients recruited by a nationwide survey of CEAS during 2012-2016 were enrolled in this present study. We reviewed the clinical information of the genetically confirmed CEAS patients. RESULTS: We identified recessive SLCO2A1 mutations at 11 sites in 46 patients. Among the 46 patients genetically confirmed as CEAS, 13 were men and 33 were women. The median age at disease onset was 16.5 years, and parental consanguinity was present in 13 patients (28%). Anemia was present in 45 patients (98%), while a single patient experienced gross hematochezia. All patients showed relatively low inflammatory markers in blood tests (median CRP 0.20 mg/dl). The most frequently involved gastrointestinal site was the ileum (98%), although no patient had mucosal injuries in the terminal ileum. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO. CONCLUSIONS: The clinical features of CEAS are distinct from those of Crohn's disease. Genetic analysis of the SLCO2A1 gene is therefore recommended in patients clinically suspected of having CEAS.

A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter.

Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn's disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of "chronic enteropathy associated with SLCO2A1 gene" (CEAS).

Chronic nonspecific multiple ulcer of the small intestine segregates in offspring from consanguinity.

BACKGROUND AND AIMS: Chronic nonspecific multiple ulcer of the small intestine is a recently proposed enteropathy characterized by persistent blood and protein loss from the small-bowel. We examined possible segregation of the disease in family pedigrees. METHODS: All cases of the disease diagnosed at our institution were reviewed with respect to particular focuses on the presence of close consanguinity in the families, the enteroscopic findings and the long-term clinical course. The diagnosis was based on persistent occult gastrointestinal bleeding and hypoproteinemia for more than 5 years, and irregularly shaped shallow ulcers in the ileum. RESULTS: During a 45-year-period, 13 patients were diagnosed as having the disease. There were 11 females and 2 males, with ages ranging from 8 to 37 years at the time of the initial presentation and with those from 13 to 38 years at the diagnosis. Enteroscopy performed in 11 patients with a time duration ranging from 0.5 to 44 years after the diagnosis revealed active ileal ulcers in 10 patients. Parents' consanguineous marriage was verified in 6 patients, two of whom also had siblings with the enteropathy. Another patient without consanguinity had a sibling with protein-losing enteropathy. CONCLUSION: Chronic nonspecific multiple ulcer of the small intestine seems to segregate in offspring from consanguineous marriage.

[Nonsteroidal anti-inflammatory drug-induced enteropathy and chronic nonspecific multiple ulcers of the small intestine].

With the development of double balloon endoscopy and video-capsule endoscopy, it has become inevitable for gastroenterologist to diagnose small intestinal ulcers accurately. Chronic nonspecific multiple ulcers of the small intestine (CNSU) and nonsteroidal antiinflammatory drugs-induced enteropathy (NSAIDs-enteropathy) share common clinicopathologic features characterized by histologically nonspecific ulcers and persistent blood loss. In addition, the two disorders had common enteroscopic findings, namely, circular ulcers and concentric stenoses. However, CNSU is distinctive of NSAIDs-enteropathy with respect to intractable ulcers of various configurations. In consideration of widespread use of NSAIDs, a strategy for the prevention of NSAIDs-enteropathy should be examined. Also, much more cases of CNSU should be analyzed to establish the pathophysiology of the disease.

Diagnosis and treatment of small-bowel stricture by double balloon endoscopy.

BACKGROUND: The source of small-bowel stricture is often difficult to diagnose due to the difficulty of placing an endoscope into the small bowel. It has recently become possible to examine the entire small bowel and perform balloon dilatation for stricture by means of double balloon endoscopy (DBE). OBJECTIVE: To identify clinical features of small-bowel stricture and determine the validity of balloon dilatation as a treatment option. DESIGN: Retrospective multicenter study. SETTING: Researchers at 7 institutions affiliated with the DBE Working Group. PATIENTS: One hundred seventy-nine patients with stricture among a total of 1035 patients who underwent DBE at the 7 institutions. INTERVENTIONS: Surgical treatment or balloon dilatation was performed as clinically indicated. MAIN OUTCOME MEASUREMENTS: Ability to detect stricture lesions by DBE, types of lesions, locations of small-bowel strictures, details of strictures, treatments for strictures, and outcomes of balloon dilatation for strictures associated with inflammatory disease. RESULTS: The total number of patients with strictures was 179. Lesions were detected within the small bowel in 156 patients. Inflammatory disease was the most common (n = 87) in patients with small-bowel stricture, and the ileum was the most common site of the inflammatory disease. Crohn's disease was the most common of the inflammatory diseases (n = 57). Balloon dilatations were performed in 31 patients with inflammatory disease, and long-term success was achieved in 22 patients. LIMITATIONS: The number of patients treated by balloon dilatation was small. CONCLUSION: DBE appears to be useful for the detection as well as treatment of small-bowel lesions.

Diagnosis and treatment of obscure GI bleeding at double balloon endoscopy.

BACKGROUND: Double balloon endoscopy (DBE) and videocapsule endoscopy (VCE) have been useful in managing obscure GI bleeding (OGIB). OBJECTIVE: This study evaluated the usefulness of DBE for diagnosis, treatment, and prognosis of OGIB and compared diagnostic yield between DBE and VCE in Japan. METHODS: Detection rates of abnormalities and diagnostic yields between VCE and DBE were compared in 74 patients at 5 centers. Of 244 patients who underwent DBE at Nagoya University Hospital, 130 (53%) with OGIB were enrolled for investigation of therapeutic procedures. SETTING: Seven Japanese medical centers. PATIENTS: Of 1034 patients who underwent DBE between September 2000 and December 2005 at 7 medical centers, 479 (46%) with OGIB were enrolled. RESULTS: Overall diagnostic yield of DBE for OGIB was 277 of 479 (58%). In patients with overt-ongoing bleeding, overt-previous bleeding of sporadic type, overt-previous bleeding of first attack only, occult bleeding with continuous positive fecal occult blood test (FOBT), or occult bleeding with 1 positive FOBT with iron deficiency anemia, diagnostic yield was 24 of 31 (77%), 179 of 310 (58%), 34 of 72 (47%), 24 of 35 (71%), and 56 of 93 (60%), respectively. Regarding positive findings in 277 patients, ulcers or erosions (53%) were the most frequent, followed by angiodysplasia (23%), tumors or polyps (22%), and diverticula (4%). Diagnoses in these patients were as follows: chronic inflammatory diseases (24%), vascular diseases (24%), tumor or polyps (21%), drug or radiation injury (7%), other small-bowel diseases (7%), upper GI diseases (9%), colorectal diseases (9%), and biliary disease (0.4%). Small-bowel diseases were confirmed in 226 patients (47%). Comparison of overall detection rate of abnormalities in the small bowel between VCE (65%) and DBE (53%) was not significantly different, nor was that of overall diagnostic yield between VCE (50%) and DBE (53%). Eight acute pancreatitis and 4 perforation episodes occurred with no mortalities at DBE. Of 130 patients at Nagoya University Hospital, 78 (60%) were diagnosed with small-bowel diseases and underwent treatments as follows: medication or observation only (n = 30), enteroscopic therapies (electrocoagulation in 21, clipping in 4, and polypectomy in 3), and surgery (n = 22). Small-bowel vascular diseases were more prone to rebleeding than small-bowel nonvascular diseases in patients without surgical treatment at a median follow-up of 423 days. CONCLUSIONS: DBE was relatively safe and useful for diagnosis and treatment of OGIB. A spectrum of small-bowel diseases presenting with OGIB in Japan may be distinct from that in the Western world.

Factors regulating tumor pressure in cases of small hepatocellular carcinoma.

BACKGROUND/AIMS: There is scare information regarding tumor pressure in hepatocellular carcinoma. As the tumor diameter increases, histological manifestations become more diverse. Therefore, studies based on relatively small tumors are needed in order to search for those underlying factors that are directly related to tumor pressure in hepatocellular carcinoma. The purpose of this study was to determine which factors regulate tumor pressure in cases of hepatocellular carcinoma where the diameter of the tumor is 3cm or less. METHODOLOGY: The study included 54 patients with small hepatocellular carcinoma in whom tumor pressure had been determined and in whom the tumor had been confirmed histologically. Tumor pressure was determined percutaneously under ultrasonographic guidance. RESULTS: Hepatic tissue pressure (p = 0.01), tumor size (p < 0.01), number of tumors (p = 0.01), degree of tumor differentiation (p < 0.01), ultrasonographic halo (p < 0.01), angiographic tumor staining (p < 0.01) and angiographic tumor vessel (p = 0.03) all showed significant correlation with tumor pressure. Multivariate analysis revealed that angiographic tumor staining (p = 0.001), hepatic tissue pressure (p = 0.013), and tumor size (p = 0.044) were significant factors associated with tumor pressure. CONCLUSIONS: It was suggested that tumor pressure in small hepatocellular carcinoma was mainly regulated through development of the neovasculature.

Differentiating enterocutaneous fistulae from suture abscesses complicating Crohn's disease using oral administration of indocyanine green.

BACKGROUND AND AIM: Clinicians encounter difficulties distinguishing enterocutaneous fistulae from postoperative suture abscesses solely by diagnostic imaging in patients with Crohn's disease. The aim of this study was to examine whether use of intraintestinal administration of indocyanine green (ICG) could differentiate the conditions. METHODS: Twenty-four patients with Crohn's disease and a possible enterocutaneous fistula at the abdominal wall based on manifestations of pus drainage and exudate were enrolled. A positive test was defined by macroscopic confirmation of staining by ICG dye, which had been administered orally, on the gauze dressing applied to the lesion site. RESULTS: Positive responses occurred in 16 of the 24 patients. In 13 of the 16 positive patients, a fistulous communication between the lesion and the gastrointestinal tract was documented by either surgery or X-ray examination. In the remaining three, fistulae were completely closed after administration of infliximab. The positive predictive value of the oral ICG test was 16/16 (100%). Six of the eight negative oral ICG test patients (75%) had subcutaneous (silk-suture) abscesses that were easily closed following fistulotomy. The other two patients had fistulas confirmed either by surgery or fistulography, indicating a false negative response from the oral ICG test. The negative predictive value of the oral ICG test was 6/8 (75%); thus, the ability of the oral ICG test to correctly diagnose was 22/24 (92%). CONCLUSIONS: This oral ICG test offers a suitable methodology for those patients possessing an occult fistulous lesion at an early stage, and where a differential diagnosis is difficult using diagnostic imaging.

[Clinical course of 4 cases of hepatic peribiliary cysts and a summary of the 38 clinical cases reported in Japan].

We encountered 4 cases of hepatic peribiliary cysts (HPBC) in our hospital. Two were asymptomatic, one was complicated by a choledocholithiasis, and one by cholangitis and sepsis. Based on a review of the 38 cases of HPBC clinically diagnosed in Japan, the main problem associated with this disease seemed incorrect preoperative diagnosis leading to an unnecessary hepatectomy. Another problem was concomitant cholangitis, which tended to recur and in some cases needed aggressive treatment using drainage.

Three-dimensional computed tomography pancreatography of an annular pancreas with special reference to embryogenesis.

OBJECTIVES: Several hypotheses have been proposed to explain the embryogenesis of an annular pancreas. Three-dimensional (3D) imaging of the annular pancreas may be useful to elucidate the embryogenesis. The aim of this case report is to clarify the pancreatic ducts in the annular pancreas by 3D computed tomography pancreatography (3D-CTP), stereographically. METHODS: Three-dimensional CTP under endoscopic retrograde pancreatography using a balloon catheter was performed with a helical CT scanner. Three-dimensional images of the pancreatic duct were obtained with simple threshold, shaped surface display. RESULTS: Wirsung duct that surrounds the ventral side of the descending portion of the duodenum and Santorini duct that surrounds the dorsal side of the descending portion of the duodenum were reconstructed by 3D-CTP, stereographically, and the presence of an annular pancreas was confirmed. These findings suggest that the formation of the annular pancreas in the current case may be attributable not only to abnormal development of the right lobe of the ventral pancreatic bud, but also to overgrowth of the dorsal pancreatic bud toward the ventral aspect of the duodenum or excessive rotation of the duodenum following fusion of the ventral bud to the dorsal bud. CONCLUSION: Three-dimensional CTP is expected to contribute usefully toward clarifying the embryogenesis of an annular pancreas.

Hemorrhagic duodenal lipoma managed by endoscopic resection.

The patient, an 81-year-old woman, was admitted to our hospital for a detailed examination; the chief complaint being melena. An upper gastrointestinal roentgenologic study revealed a submucosal tumor with a smooth surface and a stalk measuring 50 mm at the third part of the duodenum. Endoscopy depicted it as a yellowish submucosal tumor. Based on computed tomography and fluoroscopy of the small intestine, a diagnosis of duodenal lipoma was made. The esophagus, stomach, and the small and large intestines were free of lesions so the duodenal lipoma was judged to be the hemorrhagic source. The tumor was endoscopically polypectomized using a 2-channel scope. The excised specimen, measuring 50 x 20 x 20 mm, was covered by a normal duodenal mucosa with small ulcers in part. Photomicrographic findings included a tumor that was composed of mature adipose tissue in the submucosa, which coincided with a diagnosis of lipoma. Small ulcers had formed in part, exposing vessels, thus indicating the cause for hemorrhage. Lipoma is a benign tumor; and if the lesion is found to be pedunculated and an endoscope can reach it for treatment, minimally invasive endoscopic procedures should be selected.