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.

Altered serum profile of the interleukin-22 system in inflammatory bowel disease.

BACKGROUND AND AIM: Interleukin-22 (IL-22), plays a vital role in the mucosal repair of inflammatory bowel disease (IBD). Serum levels of IL-22 and IL-22 binding protein (IL-22BP), a soluble inhibitory IL-22 receptor, were measured in patients with IBD to investigate the profile of IL-22 in the systemic circulation. METHODS: Blood samples from 92 healthy subjects, 98 patients with ulcerative colitis (UC), and 105 patients with Crohn's disease (CD) were analyzed for serum levels of IL-22, IL-22BP, human ß-defensin 2 (hBD-2), and serum inflammatory parameters. Disease activity was assessed by the partial Mayo score and Harvey-Bradshaw index for UC and CD, respectively. RESULTS: Serum IL-22 level was lower in UC (P < 0.001) and CD (P < 0.001) vs control and its decrease was more pronounced in CD than in UC (P = 0.019). Serum IL-22BP level was lower in UC (P < 0.001) and CD (P < 0.001) vs control and correlated with inflammatory parameters (albumin and C-reactive protein (CRP) in UC; hemoglobin, albumin, and CRP in CD). Serum IL-22/IL-22BP ratios were higher in UC (P = 0.009) vs control and correlated with inflammatory parameters (albumin and CRP). Serum hBD-2 level was higher only in CD (P = 0.015) but did not correlate with serum IL-22 levels, IL-22BP levels, IL-22/IL-22BP ratios, or inflammatory parameters. CONCLUSIONS: Dysregulation of the IL-22 system in the blood may play a role in the pathogenesis of IBD. Further studies are needed to understand the pathogenic and clinical significance of the blood IL-22 system in IBD.

Effect of a concomitant elemental diet with maintenance anti-tumor necrosis factor-α antibody therapy in patients with Crohn's disease: A multicenter, prospective cohort study.

BACKGROUND AND AIM: The aim of this study was to clarify the additional effect of a concomitant elemental diet (ED) for patients with Crohn's disease on maintenance anti-tumor necrosis factor-α antibody (anti-TNF). METHODS: Crohn's disease patients who received anti-TNF induction therapy were enrolled. Patients who achieved clinical response (defined as delta Crohn's disease activity index [CDAI] > 70 and CDAI < 200) at 10-14 weeks after the start of infliximab or adalimumab were included. Eligible patients took a tolerability test of ED (900 kcal/day) for 3 days. Then, patients who preferred concomitant ED and whose ED tolerance was confirmed were allocated to the ED group and given Elental 900 kcal/day or more. Other patients were allocated to the non-ED group. The primary endpoint was the cumulative remission rate at 2 years after baseline. Clinical relapse was defined as CDAI > 200 and/or need for additional treatment. Adherence to the ED was confirmed at each visit. RESULTS: Seventy-two patients were included. Thirty-seven were allocated to the ED group, and 35 were allocated to the non-ED group. The cumulative remission rate at 2 years was not significantly different between the two groups (60.9% vs 56.7%, P = 0.98). Adherence to the ED in the ED group was relatively low, and only 11 patients were maintained on an ED of 900 kcal/day. CONCLUSIONS: The addition of ED for Crohn's disease patients who responded to initial anti-TNF induction therapy was not found to improve outcomes. The efficacy of concomitant ED in other clinical settings, such as loss of response, needs to be clarified in the future (UMIN000009789).

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.

[A case of a simple ulcer associated with ulcerative colitis that demonstrated a good clinical response to infliximab].

We present a case of a man in his 60s who had been in clinical remission of ulcerative colitis (UC) after treatment with 5ASA. Over the clinical course, he developed an isolated deep ulcer at the end of the ileum. There were moderate active UC findings in the rectum. We diagnosed a simple ulcer associated with UC and started treatment with azathioprine and infliximab (IFX). Shortly after the treatment, the ulcer began to scar. We report a rare case of a simple ulcer that accompanied UC, and for which IFX was effective.

Endoscopic balloon dilatation using double-balloon endoscopy is a useful and safe treatment for small intestinal strictures in Crohn's disease.

BACKGROUND: Endoscopic balloon dilatation (EBD) is a therapeutic option for intestinal strictures of Crohn's disease (CD). Double-balloon endoscopy (DBE) enables EBD to be performed even for deep-situated strictures of the small intestine. The aim of this study was to clarify the efficacy and safety of EBD using DBE for small bowel strictures in patients with CD. PATIENTS AND METHODS: The subjects comprised 25 patients with CD who underwent EBD using DBE for small intestinal strictures for which a colonoscope or gastrointestinal scope could not be inserted. All subjects had obstructive symptoms due to strictures that were confirmed using small intestinal enteroclysis. They were observed for at least 6 months after the initial EBD. The short-term success rate of EBD using DBE, the complication rate and the long-term outcome were investigated. RESULTS: This procedure was successful with regard to short-term dilatation in 18 of the 25 CD patients (72%). Long strictures measuring more than 3 cm were seen in six out of seven (85.7%) of the unsuccessful EBD cases, compared with two out of 18 (11.1%) of the successful EBD cases (P=0.001). Complications were encountered in two of the 25 patients (8%). The cumulative surgery-free rate for all the subjects was 83% and 72% at 6 and 12 months, respectively. CONCLUSION: EBD using DBE is a useful and safe procedure for small intestinal short strictures in CD patients. We conclude that this procedure is a therapeutic option that should be attempted before resorting to surgical therapy.

Novel zoom endoscopy technique for diagnosis of small flat gastric cancer: a prospective, blind study.

BACKGROUND & AIMS: During gastroscopy we frequently encounter flat reddened lesions in the stomach. Making a correct diagnosis of flat small early gastric cancer is dependent not on endoscopic diagnosis, but on histopathologic diagnosis of biopsy specimens alone. We investigated the diagnostic accuracy of magnified endoscopic findings for differentiating between reddened mucosa caused by gastritis and flat reddened gastric cancer, prospectively and blindly. METHODS: A total of 603 consecutive patients were examined by upper-gastrointestinal zoom endoscopy and the prevalence of each of the following magnified endoscopic findings, which already had been reported as characteristic for differentiated carcinoma, was recorded: (1) presence of a demarcation line between the reddened lesion and the surrounding mucosa, (2) disappearance of the regular subepithelial capillary network pattern, and (3) presence of an irregular microvascular pattern within the flat reddened lesion. Patients with known gastric carcinomas were excluded from this study. RESULTS: A total of 158 flat reddened lesions from 158 patients were detected. Pathologically, 144 flat reddened lesions showed only gastritis, whereas 14 lesions were newly diagnosed as carcinoma. Regarding diagnostic accuracy for carcinoma, the negative predictive values of the presence of a demarcation line and disappearance of the regular subepithelial capillary network pattern were 100% and 100%, respectively, and the diagnostic accuracy of the irregular microvascular pattern was 98.7%. CONCLUSIONS: The novel zoom endoscopic findings based on microvascular architecture are very useful for making a differential diagnosis between flat early gastric carcinoma and gastritis.

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.

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.

Novel zoom endoscopy technique for visualizing the microvascular architecture in gastric mucosa.

We have developed and established a zoom endoscopy technique based on visualization of the mucosal microvascular architecture in units as small as the capillary in the normal stomach and early gastric cancer. With regard to the microvascular architecture of the normal stomach, the findings differed according to the section of the stomach. The gastric body showed a honeycomb-like subepithelial capillary network pattern with collecting venule, whereas the gastric antrum showed a coil-shaped subepithelial capillary network pattern. Regarding early gastric cancer, the following findings seemed to be specific for differentiated carcinoma: (1) a demarcation line between the cancerous and the noncancerous mucosa, (2) the disappearance of the regular subepithelial capillary network pattern, and (3) the presence of an irregular microvascular pattern. These findings, which were visualized by magnified observation, could be useful in clinical practice when we attempt to make a correct endoscopic diagnosis of flat reddened lesions (gastritis vs cancer) and when we attempt to determine the precise horizontal margin of early gastric cancer. This could help us to perform successful endoscopic resection based on endoscopic findings alone. In conclusion, our zoom endoscopy for visualizing the microvascular architecture in gastric mucosa could be a new system for diagnosing early gastric cancer.

Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial.

Acute hepatitis C often progresses to chronic infection. We undertook a randomized controlled trial to determine whether short-term therapy with interferon (IFN) during acute hepatitis C is effective in preventing the development of chronic hepatitis. Thirty patients with acute hepatitis C were randomized into 1 of 2 treatment groups. IFN therapy was initiated 8 weeks after the onset of acute hepatitis in the early-intervention group and after 1 year of observation in the late-intervention group. Short-term therapy consisted of natural IFN-alfa (6 million units) administered on consecutive days for a period of 4 weeks. Any signs of recrudescence of disease were immediately followed by interval IFN therapy (3 times weekly for 20 weeks). In the early-intervention group, short-term therapy was associated with a sustained virological response in 13 of 15 patients (87%). Follow-up treatment was associated with a sustained virological response in both of the remaining 2 patients (100%). The sustained virological response rate was significantly higher in the early-intervention group (87%, 13 of 15 patients after short-term therapy alone, and 100%, 15 of 15 patients after short-term with or without follow-up therapy) than in the late-intervention group (40%, 6 of 15 patients after short-term therapy alone, and 53%, 8 of 15 patients after short-term therapy with or without follow-up therapy, P =.021 and P =.006, respectively). In conclusion, short-term (4 weeks) IFN treatment of patients with acute hepatitis C may be associated with satisfactory results, if initiated at an early stage of the disease.

Efficacy of early retreatment with interferon beta for relapse in patients with genotype Ib chronic hepatitis C.

BACKGROUND: Interferon (IFN) retreatment for hepatitis C virus (HCV) relapsers has been effective under some conditions. We conducted a randomized, controlled trial of IFN beta retreatment for HCV relapsers after IFN alpha. PATIENTS AND METHODS: We gave IFN beta 6MIU therapy to 43 patients who had relapse of HCV after the 24 weeks IFN alpha monotherapy. The 43 patients were randomly assigned to two groups: Group A started retreatment within 4 weeks after relapse; and Group B started retreatment 24 weeks or more after relapse. RESULTS: Nine patients showed sustained virological response (SR) to the retreatment. All of these patients were in a low viral load subgroup. The SR rate in Group A (8/22, 36%) was significantly higher than in Group B (1/21, 5%) (P=0.0128). Among patients with lower viral load, the SR rate in Group A (8/10, 80%) was also significantly higher than in Group B (1/8, 13%) (P=0.0076). CONCLUSION: The retreatment with IFN beta is effective for patients with HCV low viral load, and the sooner after the relapse the retreatment is started, the better the clinical results will be.

Pilot study of prolonged interferon-alpha retreatment in chronic hepatitis C patients with genotype 1b.

OBJECTIVES: To investigate the efficacy of prolonged IFN retreatment for 3 years in chronic hepatitis C patients with high viral load and IFN treatment-resistant genotype 1b. PATIENTS AND METHODS: The study was conducted in 12 patients, not HCV RNA-negative after completion of the initial treatment. Retreatment consisted of administration of 6 million international units (MIU) of natural interferon-alpha, two or three times a week for 3 years. RESULTS: One patient was withdrawn for personal reasons. All other 11 patients completed treatment without any serious adverse reactions and were followed for 3 years. Of the patients, 4 (36%) showed a sustained virological response, 5 (45%) showed a biochemical response, and 2 (18%) relapsed after retreatment. All patients with a sustained response had a transient response to initial therapy. Patients showing a sustained response tested negative for HCV RNA within the first 6 months of retreatment. CONCLUSIONS: After prolonged IFN retreatment, a significant number of patients showed a sustained response for the first time and long-term improvement in ALT level.