Duodenal cancer diagnosed by capsule endoscopy and double balloon enteroscopy in a patient with hereditary nonpolyposis colorectal cancer.
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Biomedical subjects
Kazuhide Higuchi
Publications and source records attributed to Kazuhide Higuchi.
Successful treatment of giant rectal varices by modified percutaneous transhepatic obliteration with sclerosant: Report of a case.
We present a female patient with continuous melena, diagnosed with rectal variceal bleeding. She had a history of esophageal varices, which were treated with endoscopic therapy. Five years after the treatment of esophageal varices, continuous melena occurred. Since colonoscopy showed that the melena was caused by giant rectal varices, we thought that they were not suitable to receive endoscopic treatment. We chose the modified percutaneous transhepatic obliteration with sclerosant, which is one of the interventional radiology techniques but a new clinical procedure for rectal varices. After the patient received this therapy, her condition of rectal varices was markedly improved.
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Regression of primary low-grade mucosa-associated lymphoid tissue lymphoma of duodenum after long-term treatment with clarithromycin.
A 74-year-old woman was referred to our department because of epigastralgia. Endoscopic findings revealed yellowish bumpy mucosa from the bulbus to the second portion of the duodenum. The patient was admitted to our hospital for further examinations and treatment for this lesion. Endoscopic mucosal resection (EMR) was performed on part of the lesion to obtain the final diagnosis, and then mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum was diagnosed using this procedure. In this case, no evidence of Helicobacter pylori infection in the patient's stomach was detected by any of the diagnostic examinations used, such as the urea breath test, histological study, culture, and serological antibody. For this reason, the patient's duodenal MALT lymphoma was treated solely with long-term clarithromycin, which had an inhibitory action on lymphocyte activation. The lesion showed slight improved during the first 12 days of treatment, and complete regression was reached after 6 months of treatment. It is suggested that the long-term use of clarithromycin may be effective for diseases of the gastrointestinal tract associated with the lymphocyte proliferation.
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Close association between activated platelets and neutrophils in the active phase of ulcerative colitis in humans.
BACKGROUND: Neutrophils are considered to play a causative role in inflammatory mucosal injury in ulcerative colitis (UC), and an association between platelets and neutrophils may contribute to the progression of the inflammatory processes. To test this hypothesis, we performed immunohistochemical and flow cytometric analyses on tissue and blood samples from patients with UC. MATERIALS AND METHODS: Colonic mucosal tissues of patients with active (n = 27) or inactive (n = 16) UC and normal controls (n = 11) were subjected to immunohistochemical staining for markers of activated platelets (glycoprotein IIb/IIIa and P-selectin) and neutrophils (neutrophil elastase, myeloperoxidase, and CD66b). The amounts of stained cells were evaluated by computer-aided morphometry. Peripheral blood samples from patients (n = 8) and healthy volunteers (n = 8) were subjected to comparative flow cytometric analysis of activated platelets. RESULTS: P-selectin-positive activated platelets were frequently aggregated in the inflamed mucosa, especially in ulcerative lesions, and were close to regions of dense neutrophil infiltration. An increase in the number of activated platelets in the colonic lesions was associated with an increase in infiltrating neutrophils and was related to the severity of the disease. The flow cytometric analysis indicated that circulating platelets of patients with UC were highly activated. CONCLUSIONS: The present study demonstrated that a close association between activated platelets and neutrophils is a prominent pathological change in both the affected colonic mucosa and peripheral blood of patients with active-phase UC. This suggests that platelet-neutrophil association may play an important role in the progression of inflammatory processes in UC.
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Slow-wave photic stimulation relieves patient discomfort during esophagogastroduodenoscopy.
BACKGROUND AND AIM: Although pretreatment with a sedative drug is effective in relieving pain during esophagogastroduodenoscopy (EGD), such drugs can cause significant side-effects. The aim of this study was to examine the effect of slow-wave photic stimulation on discomfort and/or pain felt during EGD. METHODS: Forty consecutive patients (25 men and 15 women) who underwent diagnostic EGD in our hospital were included in the study. Twenty patients received photic stimulation for 25 min, and underwent electroencephalographic recording, in addition to the usual premedications. Twenty control patients received the same treatment but without photic stimulation. All patients evaluated the discomfort/pain felt during endoscopy against a five-grade scale in comparison with what they had experienced in their previous examination. RESULTS: Patients with an improved discomfort/pain score were 18/20 and 3/20 in the treated and control groups, respectively. Overall comparison of pain scores between both groups was significant (P<0.0001). The proportion of slow-wave activity recorded in patients' electroencephalograms significantly increased in the treated group compared to control values (36.6+/-6.8% vs 29.1+/-3.4%, P<0.001). There was a close correlation between the degree of discomfort/pain felt during endoscopy and the proportion of slow-wave activity (P<0.001). CONCLUSION: Slow-wave photic stimulation shows promise as a treatment for relieving the discomfort and/or pain felt by patients undergoing EGD.
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Production of reactive oxygen species in peripheral blood is increased in individuals with Helicobacter pylori infection and decreased after its eradication.
BACKGROUND: Helicobacter pylori infection has been reported to cause gastroduodenal ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Recent studies have suggested that H. pylori infection may also associate with other diseases, including hematologic and dermatologic disorders, and cardiovascular injury, by unknown mechanisms. METHODS: Production of reactive oxygen species (ROS) was determined in peripheral blood samples from 86 patients (34 H. pylori-negative and 52 H. pylori-positive subjects) using a highly sensitive chemiluminescence probe, L-012 (8-amino-5-chloro-7-phenylpyrido(3,4-d) pyridazine-1 and 4 (2H, 3H) dione). Eleven H. pylori-positive individuals were also analyzed their ROS production in peripheral blood after H. pylori eradication. RESULTS: ROS production was significantly higher in individuals with H. pylori infection than in those without infection. Enhanced production of ROS was decreased significantly after eradication of H. pylori. No correlation was found between the extent of ROS production and sex, age, smoking status, alcohol ingestion, use of medications, or serum level of C-reactive protein. CONCLUSION: These findings suggest that ROS production was enhanced in peripheral blood by H. pylori infection. Chemiluminescence analysis of blood samples using L-012 permits evaluation of systemic oxidative stress in patients with H. pylori infection.
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Evaluation of deep small bowel involvement by double-balloon enteroscopy in Crohn's disease.
OBJECTIVES: Double-balloon enteroscopy (DBE) enables inspection of deep small bowel, and total small bowel examination can be performed by either antegrade or retrograde DBE. The aim of this study was to evaluate ileal involvement, which cannot be achieved using conventional colonoscopy, by DBE in patients with Crohn's disease. METHODS: From December 2003 to September 2005, a total of 44 patients with Crohn's disease underwent 53 examinations using DBE. RESULTS: Forty patients with Crohn's disease, seven women and 33 men, underwent DBE, and the ileum was investigated in 38 patients. There were 25 cases of ileitis, 2 of colitis, and 13 of ileocolitis. Jejunal lesions were found in two and ileal lesions proximal to the terminal ileum were found in 24 patients with Crohn's disease. DBE was superior to radiological study to detect aphthae, erosions, and small ulcers in the ileum. Small bowel stricture was demonstrated in six and nine patients with DBE and small bowel barium study (SBBS), respectively. An additional mucosal finding was demonstrated in one of the eight patients who underwent wireless capsule endoscopy, and one patient had a capsule removed by DBE that had become lodged because of an ileal stricture. One ileal perforation because of overtube balloon pressure occurred in 53 examinations of patients with Crohn's disease (1.9%). CONCLUSION: DBE is useful to evaluate small bowel lesions in patients with Crohn's disease; however, special attention should be paid to mesenteric longitudinal ulcers during insertion and the overtube balloon should not be inflated if a clear intestinal view is not possible.
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Efficacy and safety of Helicobacter pylori eradication therapy with omeprazole, amoxicillin and high- and low-dose clarithromycin in Japanese patients: a randomised, double-blind, multicentre study.
OBJECTIVE: Seven-day administration of omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day is currently approved in Japan for the eradication of Helicobacter pylori infection. We investigated the efficacy and safety of an omeprazole-based triple therapy regimen in combination with amoxicillin and low-dose clarithromycin in Japanese patients. METHODS: Patients were randomly assigned to either the low-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 400 mg/day) or the high-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day). A total of 288 patients were allocated to the low-dose (143) and high-dose (145) groups and were treated twice daily for 1 week. RESULTS: For the full-analysis set, H. pylori eradication rates were 81.1% (116/143 patients, 90% confidence interval [CI] 74.9, 86.3) in the low-dose group and 80.0% (116/145 patients, 90% CI 73.7, 85.3) in the high-dose group. Per-protocol eradication rates were 81.7% (103/126 patients, 90% CI 75.1, 87.2) and 84.1% (90/107 patients, 90% CI 77.1, 89.6), respectively. When patients with non-susceptibility to clarithromycin were excluded, eradication rates were >80% for both gastric and duodenal ulcers in the two groups. The results suggested that eradication rates were affected more by susceptibility to clarithromycin than to amoxicillin. Both regimens were well tolerated. CONCLUSION: This study demonstrated that an omeprazole-based triple-therapy regimen with clarithromycin 400 mg/day was as effective as that with clarithromycin 800 mg/day for H. pylori eradication.
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[Rumination syndrome in an adult with normal intelligence].
A 32-year-old woman visited our department because of repeated regurgitation of food, and was diagnosed with rumination syndrome based on possession of symptoms typical for it. Although rumination syndrome is classified as a functional esophageal disorder according to the Rome II criteria, it is not well known in Japan, and there have been no previous reports of it in an adult with normal intelligence. Since patients with rumination syndrome are often misdiagnosed and receive unnecessary treatment, awareness of it by physicians is important.
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[Post infectious irritable bowel syndrome experimental model].
Irritable bowel syndrome may be consisted of several subsets of functional disorders including a subset of post inflammatory and post infectious disorders. Animal models revealed prolonged hyper-kinesis of the intestinal muscle and visceral hyperalgesia in adult mice previously received phychological stress or bowel irritation in neonatal period. Murine infectious experiment reproduced adult post infectious functional disorders. Involvement of acute phase Th2 cytokine production and prolonged TGFbeta1 production contribute to intestinal hyper-kinesis in post nematode infectious rat model. Pathogenesis of irritable bowel syndrome may be further subdivided by the results of experimental models, and a novel therapeutic approach is expected from such experimental models.
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Risk factors for bleeding after endoscopic mucosal resection.
AIM: To clarify the risk factors for bleeding after endoscopic mucosal resection (EMR). METHODS: A total of 297 consecutive patients who underwent EMR were enrolled. Some of the patients had multiple lesions. Bleeding requiring endoscopic treatment was defined as bleeding after EMR. Odds ratios (OR) with 95% confidence intervals (CI), calculated by logistic regression with multivariate adjustments for covariates, were the measures of association. RESULTS: Of the 297 patients, 57 (19.2%) patients with bleeding after EMR were confirmed. With multivariate adjustment, the cutting method of EMR, diameter, and endoscopic pattern of the tumor were associated with the risk of bleeding after EMR. The multivariate-adjusted OR for bleeding after EMR using endoscopic aspiration mucosectomy was 3.07 (95%CI, 1.59-5.92) compared with strip biopsy. The multiple-adjusted OR for bleeding after EMR for the highest quartile (16-50 mm) of tumor diameter was 5.63 (95%CI, 1.84-17.23) compared with that for the lowest (4-7 mm). The multiple-adjusted OR for bleeding after EMR for depressed type of tumor was 4.21 (95%CI, 1.75-10.10) compared with elevated type. CONCLUSION: It is important to take tumor characteristics (tumor size and endoscopic pattern) and cutting method of EMR into consideration in predicting bleeding after EMR.
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Roles of epidermal growth factor and Na+/H+ exchanger-1 in esophageal epithelial defense against acid-induced injury.
Epidermal growth factor (EGF) is predominantly secreted by salivary glands and activates Na(+)/H(+) exchanger-1 (NHE-1), which regulates intracellular pH (pH(i)). We investigated the roles of EGF and NHE-1 in esophageal epithelial defense against acid using human esophageal epithelial cell lines and a rat chronic esophagitis model. Esophageal epithelial cells were incubated with acidified medium in the absence or presence of EGF. Cell viability and changes in pH(i) were measured. Chronic acid reflux esophagitis was induced in rats with and without sialoadenectomy. Esophageal lesion index, epithelial proliferation, and expression of EGF receptors and NHE-1 were examined. EGF protected esophageal epithelial cells against acid in a dose-dependent manner, and the cytoprotective effect of EGF was completely blocked by treatment with NHE-1 inhibitors. Tyrosine kinase, calmodulin, and PKC inhibitors significantly inhibited cytoprotection by EGF, whereas MEK, phosphatidylinositol 3-kinase, and PKA inhibitors had no effect. EGF significantly increased pH(i) recovery after NH(4)Cl pulse acidification, and this increase in pH(i) recovery was significantly blocked by inhibitors of calmodulin and PKC. Sialoadenectomy led to an increase in the severity of chronic esophagitis but affected neither epithelial proliferation nor expression of EGF receptors. Expression of NHE-1 mRNA was increased in esophagitis and upregulated in rats with sialoadenectomy. The increasing severity of esophagitis in rats with sialoadenectomy was prevented by exogenous administration of EGF. In conclusion, EGF protects esophageal epithelial cells against acid through NHE activation via Ca(2+)/calmodulin and the PKC pathway. Deficiency in endogenous EGF is associated with increased severity of esophagitis. EGF and NHE-1 play crucial roles in esophageal epithelial defense against acid.
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15th anniversary of rebamipide: looking ahead to the new mechanisms and new applications.
Rebamipide, a gastro-protective drug, was developed in Japan for the treatment of peptic ulcer disease. It was proven superior to the former same category drug cetraxate in a randomized, controlled, double-blind, comparative clinical study in 1989. Rebamipide's mechanisms of actions are different from anti-secretory drugs; it accelerates and improves the quality of ulcer healing and reduces ulcer recurrence rate. Numerous studies have been conducted to explain the mechanisms responsible for these actions, 37 papers were published by 1998. Major properties of rebamipide include: stimulation of prostaglandin and mucus glycoprotein synthesis, inhibition of reactive oxygen species, inflammatory cytokines and chemokines, and inhibition of neutrophils activation. Since 1998, 107 papers were published, clarifying further effects of rebamipide on cyclooxygenase-2, prostaglandin E receptors, growth factors (i.e., HGF, EGF, and VEGF), heat-shock proteins, nitric oxide, adhesion molecules, neutrophils, and Helicobacter pylori- and NSAID-related pathology. Moreover, inhibitory action of rebamipide on gastric cancer growth has also been shown. In this issue we reviewed recent advances in understanding of rebamipide's mechanism of action and its newest clinical applications.
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Rebamipide reduces delay in gastric ulcer healing in cyclooxygenase-2-deficient mice.
Rebamipide is an antiulcer drug capable of various actions including the induction of cyclooxygenase-2 (COX-2). In this study, we investigated the effect of rebamipide on gastric ulcer healing in COX-2-deficient mice. Wild-type (N=34) and COX-2-deficient mice (N=28) with gastric ulcers were administered 30 mg/kg of rebamipide or the vehicle. Ulcerous tissues were subjected to measurements of ulcer size, immunohistochemical staining of CD31 (an endothelial cell marker), and mRNA levels. COX-2 deficiency delayed ulcer healing and inhibited angiogenesis and bFGF mRNA expression in the granulation tissue. In wild-type mice, rebamipide accelerated ulcer healing and increased COX-2 mRNA expression. In COX-2-deficient mice, rebamipide prevented delayed ulcer healing and reversed the inhibition in angiogenesis and bFGF mRNA expression. The effect of rebamipide on the enhancement of ulcer healing, angiogenesis, and induction of bFGF expression was more prominent in wild-type mice than in COX-2-deficient mice. In conclusion, rebamipide may accelerate gastric ulcer healing through both COX-2-dependent and COX-2-independent mechanisms.
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Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan.
BACKGROUND AND AIM: Epidemiological studies have shown that 10-48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects. METHODS: A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self-report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week. RESULTS: Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety-nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD. CONCLUSION: Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.
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Association between dinner-to-bed time and gastro-esophageal reflux disease.
OBJECTIVE: It is generally recommended that patients with gastro-esophageal reflux disease (GERD) refrain from eating within 3 h of going to sleep. In addition to a remarkable lack of supporting clinical evidence, whether GERD patients have shorter dinner-to-bed time is unknown. This study was designed to determine a possible association between dinner-to-bed time and GERD, compared with healthy adults. METHODS: In a matched case-control study, we enrolled 147 GERD patients, and age- and sex-matched 294 controls without GERD symptoms such as heartburn and acid regurgitation during the previous year. Dinner-to-bed time, defined as the time intervals until going to bed after finishing eating dinner, was examined by a self-report questionnaire. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (CI) for GERD. RESULTS: After adjustment for smoking habits, drinking habits, and body mass index, shorter dinner-to-bed time was significantly associated with an increased OR of GERD (p < 0.0001) and the OR for patients whose dinner-to-bed time was less than 3 h was 7.45 (95% CI 3.38-16.4) compared with patients whose dinner-to-bed time was 4 h or more. These observations were consistent in both patients with non-erosive GERD and erosive esophagitis, and there was no significant difference in dinner-to-bed time intervals between non-erosive GERD and erosive esophagitis. CONCLUSION: In this matched case-control study, shorter dinner-to-bed time was significantly associated with an increased OR for GERD.
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Differences in clinical characteristics between patients with endoscopy-negative reflux disease and erosive esophagitis in Japan.
OBJECTIVE: Helicobacter pylori infection and atrophic gastritis are inversely related to erosive esophagitis. Whether these factors affect the pathogenesis of endoscopy-negative reflux disease is not clear. We aimed to elucidate the differences in clinical characteristics between endoscopy-negative erosive disease and erosive esophagitis. METHODS: 253 subjects (89 with endoscopy-negative reflux disease and 164 with erosive esophagitis) were studied. Gastric atrophy was assessed by measurement of serum pepsinogen. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) of endoscopy-negative reflux disease compared with erosive esophagitis. RESULTS: Among GERD patients, female gender (OR = 2.27, 95% CI, 1.25-4.10), smoking (OR = 0.45, 95% CI, 0.22-0.91), and the presence of hiatal hernia (OR = 0.30, 95% CI, 0.17-0.56) were significantly associated with endoscopy-negative reflux disease compared with male gender, not smoking, and absence of hiatal hernia, respectively. Body mass index (BMI) was also significantly associated with a decreased OR for endoscopy-negative reflux disease. Although H. pylori infection and gastric atrophy were significantly more common in patients with endoscopy-negative reflux disease, these associations did not persist in a multiple-adjustment model. After adjustment for gender, BMI, smoking, and hiatal hernia, a decrease in serum pepsinogen I/II ratio was significantly associated with an increased OR for endoscopy-negative reflux disease (p for trend = 0.018). CONCLUSIONS: Female gender, low BMI, not smoking, absence of hiatal hernia, and severity of gastric atrophy were positively associated with endoscopy-negative reflux disease compared with erosive esophagitis among Japanese patients.
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AP-1 and colorectal cancer.
Activator protein-1 (AP-1) is a transcription factor that consists of either a Jun-Jun homodimer or a Jun-Fos heterodimer. AP-1 regulates the expression of multiple genes essential for cell proliferation, differentiation and apoptosis. Numerous reports suggest that AP-1 plays an important role in various human diseases. Among them, the roles relating to human cancers have been strongly suggested for a long time. In human cancers, colorectal cancer is still a leading cause of morbidity and mortality in the world. Since there are some reports about the role of AP-1 in colorectal cancer response to a number of stimuli, such as cytokines and growth factors, and oncogenictransformation, therapeutic inhibition of AP-1 activity has attracted considerable interest. Here, we demonstrate the biological properties of AP-1 and its role in colorectal cancer, and discuss a possibility of an AP-1 inhibitor, an adenovirus dominant-negative mutant of c-Jun, as a therapeutic agent for gene therapy.
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