林 芳和

AIM: To identify a predictor of successful primary Helicobacter pylori (H. pylori) eradication assessed in routine clinical practice. METHODS: From February 2013 to January 2015, 186 patients underwent primary eradication therapy. We retrospectively reviewed the medical records. All patients underwent EGD before eradication therapy and H. pylori infection was diagnosed by ≥10 U/mL serum anti-H. pylori IgG. We used standard triple therapy including a proton pump inhibitor (PPI) (rabeprazole 10 mg or lansoprazole 30 mg), clarithromycin 200 mg and amoxicillin 750 mg twice daily for seven days. To determine if eradication succeeded, a 13C-urea breath test was performed on all patients more than eight weeks after primary eradication. RESULTS: The overall success rate of H. pylori eradication therapy was 62% (116/186). We assessed potential predictors of successful primary H. pylori eradication therapy including gender, age, smoking habits, prior PPI intake, kind of PPI, serum IgG value and degree of atrophy. Univariate analysis showed that high serum IgG significantly predicts successful eradication (odds ratio (OR) 2.583, 95% confidence interval (CI) 1.285-5.191, p=0.008). The eradication rate was 77% (43/56) in the ≥45 U/mL group and 56% (73/130) in the &lt 45 U/ mL group, and significance was confirmed by multivariate analysis (OR 2.626, 95% CI 1.269-5.436, p=0.009). Multivariate analysis showed a trend that advanced age (≥70 year-old) increased the rate of successful eradication (OR 1.669, 95% CI 0.857-3.252, p=0.132). CONCLUSION: Elevated serum IgG significantly predicts successful primary H. pylori eradication.

Pulmonary complications of ulcerative colitis (UC) are relatively rare. Generally, pulmonary lesions with cavity formation are difficult to distinguish from infections or Wegener's granulomatosis lesions. A 15-year-old female with no remarkable past medical history had multiple pulmonary nodules on chest X-ray. Since empirical treatment with wide-spectrum antibiotics did not improve her symptoms, she was transferred for further evaluation. Chest radiography and computed tomography (CT) scan showed multiple bilateral pulmonary nodules with cavity formation, 8-65 mm in diameter, located mainly in the right lung. She was diagnosed with UC based on sigmoidoscopy. She was treated with mesalazine and granulocyte-monocyte apheresis (GMA). Steroids were not administered, because an infectious disease could not be excluded. Seven days after starting GMA, her symptoms and laboratory findings improved, and she was discharged. After the completion of 10 courses of GMA, chest radiography and CT scan showed marked diminution of the pulmonary lesions. UC-associated pulmonary lesions can be treated without steroid administration, and we suggest that this strategy is an option for a patient with UC-associated pulmonary lesions that cannot be differentiated from an infection.

BACKGROUND: Double-balloon endoscopy (DBE) has become a new standard in enteroscopy. However, it may be difficult to make a diagnosis or plan treatment strategy with endoscopic visualization alone. The addition of endoscopic ultrasonography (EUS) has the potential to improve the ability to establish the diagnosis and develop a treatment strategy. The present study was conducted to assess the feasibility and usefulness of EUS with DBE. METHODS: EUS with DBE was performed in 31 of 891 patients who underwent DBE from July 2004 to March 2011 at Jichi Medical University Hospital. We analyzed the EUS findings for lesions and evaluated the usefulness of EUS considering the following three factors: qualitative diagnostic value for lesions, depth grading of lesions, and evaluation of the structure of severe strictures prior to endoscopic balloon dilation. RESULTS: EUS was performed for 31/32 lesions (97%) in 31 patients. EUS findings were informative for 29/32 lesions (91%). EUS findings were useful for establishing a qualitative diagnosis in 15/25 lesions (60%). EUS findings for depth grading provided useful information for determining the therapeutic strategy in 11/13 lesions (85%). EUS with DBE was useful in the evaluation of strictures for all six lesions (100%). The overall usefulness of EUS with DBE on decision making was 72% (23/32) in this study. CONCLUSIONS: EUS with DBE is feasible and useful. It provides additional information on small-bowel disease and contributes to establishing a precise diagnosis and selection of an appropriate therapeutic strategy.

BACKGROUND: GI bleeding secondary to small-intestine vascular lesions (SIVLs) is associated with rebleeding despite initial hemostasis by endotherapy applied at double-balloon endoscopy (DBE). OBJECTIVE: To evaluate the long-term outcomes of DBE endotherapy of SIVL (as described by the Yano-Yamamoto classification). The impact of repeat DBE endotherapy for recurrent bleeding also was assessed. DESIGN: Retrospective cohort study. The mean (± standard deviation [SD]) follow-up period was 4.9 (± 1.7) years (range 2.4-9.1 years). SETTING: Tertiary-care referral center. PATIENTS: A total of 43 patients, who underwent 69 sessions of DBE endotherapy of SIVLs. INTERVENTION: DBE endotherapy. MAIN OUTCOME MEASUREMENTS: Frequency of overt rebleeding after the initial DBE endotherapy. RESULTS: Overt rebleeding occurred in 16 of 43 patients (37%). Patients with multiple SIVLs showed a significantly higher rate of overt rebleeding than did those with a solitary SIVL (12/23 [52%] vs 4/20 [20%]; P = .017). The trend toward frequency of rebleeding after the first DBE hemostasis appeared to be higher for patients with type 1a SIVLs than for those with type 1b or type 2 lesions: type 1a (8/16, 50%) versus type 1b (5/19, 26%) (P = .12) and type 1a (8/16, 50%) versus type 2 (2/7, 29%) (P = .31), respectively. In 12 of 16 patients (75%) who underwent repeat DBE endotherapy at each episode of overt rebleeding (median 3 times, range 2-6), the frequency of rebleeding decreased significantly after the first year of follow-up, as compared with the remaining 4 patients who did not undergo repeat DBE; mean (± SD) 0.12 (± 0.19) versus 0.52 (± 0.33) times per year per patient (P = .006). LIMITATIONS: Single-center, retrospective study. CONCLUSION: Although the presence of multiple SIVLs was associated with rebleeding, repeat DBE endotherapy resulted in an improved long-term outcome in patients with refractory SIVL bleeding.

Human intestinal spirochetosis (HIS) is a colorectal infectious disease caused by Brachyspira species. We describe HIS in an immunocompromised, 62-year-old Japanese man who presented at Jichi Medical University Hospital with symptoms of diarrhea and bloody stool. He had rheumatoid arthritis that had been treated with immunosuppressive drugs for 10 years. Colonoscopy revealed multiple erythematous spots in the cecum and colon. A histopathological examination identified intestinal colonization by spirochetes, and Brachyspira pilosicoli was isolated from biopsy specimens, indicating a diagnosis of HIS. Metronidazole eradicated the spirochetes, the intestinal mucosa recovered to normal, and the clinical symptoms disappeared. This case suggests that it is important to keep in mind HIS in the differential diagnosis of immunocompromised patients with chronic diarrhea and bloody stool.

BACKGROUND: The major problem in the management of Peutz-Jeghers syndrome (PJS) is small-bowel polyps, which can cause intussusception and bleeding. Double-balloon endoscopy (DBE) enables endoscopic resection of small-bowel polyps. OBJECTIVE: The aim of this study was to determine the efficacy and safety of endoscopic management of small-bowel polyps in PJS patients by using DBE. DESIGN: Retrospective chart review. SETTING: Single university hospital. PATIENTS: Consecutive patients with PJS who underwent multiple sessions of DBE for evaluation or treatment of small-bowel polyps between September 2000 and April 2009. INTERVENTIONS: Endoscopic resection of small-bowel polyps in PJS patients was performed by using DBE. MAIN OUTCOME MEASUREMENTS: Efficacy, safety, and long-term laparotomy rate after the procedures were evaluated. RESULTS: Fifteen patients (10 men, mean age 34.0 ± 15.8 years) underwent DBE for a mean 3.0 ± 1.0 sessions. The mean numbers of resected polyps larger than 20 mm significantly decreased as sessions advanced (first, 3.6; second, 1.3; third, 0.7; fourth, 0.4; and fifth, 1.0; P = .02). The mean maximum sizes of resected polyps also significantly decreased at each session: 33, 19, 12, 17, and 30 mm (P = .01). One patient had a perforation, but was managed conservatively. Other complications were pancreatitis (n = 2) and bleeding (n = 2). Only 1 patient underwent surgery for intussusception during the study period. LIMITATIONS: This was a small single-center retrospective study of short duration. CONCLUSIONS: Endoscopic management of small-bowel polyps in PJS patients by using DBE is safe and effective and avoids urgent laparotomy.

BACKGROUND & AIMS: It is often difficult to determine the cause of obscure gastrointestinal bleeding (OGIB). We evaluated the diagnostic yield and long-term outcome of patients with OGIB by using double-balloon endoscopy (DBE). METHODS: In this large, retrospective cohort study, DBE was performed in 200 consecutive patients with OGIB. Follow-up data were available from 151 patients for 29.7 months (range, 6-78 months), and clinical outcome was assessed. RESULTS: DBE detected bleeding sources in 155 of 200 patients (77.5%). The most frequent source detected was small intestine ulcers/erosions (64 patients). Patients who underwent DBE within 1 month after the last episode of overt bleeding had a better yield of positive findings than those who did not (84%, 107/128 patients vs 57%, 24/42; P = .002). The overall rate of control of OGIB was 64% (97/151 patients). Patients with vascular lesions of the small intestine had a significantly lower rate of control of OGIB than those with other small intestine lesions (40%, 12/30 patients vs 74%, 52/70; P = .001). A requirement for a large transfusion before DBE (P = .012), multiple lesions (P = .010), and suspicious (not definite) lesions (P = .038) each significantly increased the likelihood of overt rebleeding in patients with vascular lesions of the small intestine. CONCLUSIONS: DBE is useful for the diagnosis of patients with OGIB and should be performed as soon as possible after overt OGIB. Patients with vascular lesions of the small intestine should be followed with particular care.

BACKGROUND: Although double-balloon enteroscopy (DBE) is performed increasingly often in adults, few findings are available on the use of DBE in pediatric patients in the published literature. OBJECTIVES: The aim of our study was to evaluate the safety and efficacy of DBE in pediatric patients. DESIGN: A retrospective database review. SETTING AND PATIENTS: A database analysis was performed on all pediatric patients (18 years old or younger) who underwent DBE at the Jichi Medical University Hospital between September 2000 and October 2008 selected from a total of 825 patients. MAIN OUTCOME MEASUREMENTS: Clinical utility and safety of DBE in pediatric patients. RESULTS: A total of 92 procedures were performed in 48 patients (27 male, 21 female) with a median age (range) of 12.2 (4-18) years. DBE was performed with the patients under general anesthesia in 43 procedures and under moderate sedation in 49 procedures. The most common indication for DBE was treatment of a stricture of a biliary anastomosis after living-donor liver transplantation with establishment of Roux-en-Y hepaticojejunostomy (23 patients). Endoscopic retrograde cholangiography using DBE was performed, and endoscopic therapy could be performed successfully in 13 (56%) patients. The second most common indication was obscure GI bleeding (10 patients); the lesions responsible for the bleeding were found in 7 (70%) patients. Other indications included surveillance and treatment of hereditary polyposis syndromes (5 patients), abdominal pain (4 patients), and inflammatory bowel disease (2 patients). The overall diagnostic yield was 65% (31 of the 48 patients). Postpolypectomy bleeding occurred in 1 case, but no other complications such as perforation and pancreatitis were observed. LIMITATIONS: Small number of patients, participation bias, and single center's experience. CONCLUSIONS: DBE is a safe and clinically useful endoscopic procedure in pediatric patients.

The new methods of capsule endoscopy (CE) and double-balloon endoscopy (DBE) have revolutionized the diagnostic approach to middle (mid) gastrointestinal bleeding (MGIB) in recent years. DBE also has therapeutic options and enables us to treat the MGIB endoscopically. In this review, we discuss endoscopic diagnosis and management of three major categories of sources of MGIB - vascular lesions, ulcers/erosions and tumors/polyps.

BACKGROUND: The diagnostic accuracy of conventional endoscopy for small colonic polyps is not satisfactory. Optimal band imaging (OBI) enhances the contrast of the mucosal surface without the use of dye. OBJECTIVE: To evaluate the diagnostic accuracy for the differentiation of neoplastic and non-neoplastic colorectal polyps by using magnified OBI colonoscopy. DESIGN: An open prospective study. SETTING: Jichi Medical University, Japan. PATIENTS: A total of 133 colonoscopy cases. MAIN OUTCOME MEASUREMENT: A comparative study of the overall accuracy, sensitivity, and specificity for the differentiation of neoplastic and non-neoplastic colorectal polyps < or =5 mm in size by capillary-pattern diagnosis by using conventional colonoscopy, capillary-pattern diagnosis in OBI, and pit-pattern diagnosis in chromoendoscopy with low magnification. RESULTS: A total of 107 polyps, composed of 80 neoplastic and 27 non-neoplastic polyps, were evaluated. OBI clearly showed the capillary network of the surface mucosa of neoplastic polyps at low magnification, whereas the surface mucosa of non-neoplastic polyps showed up as a pale lesion. The capillary pattern in conventional colonoscopy had 74% accuracy, 71% sensitivity, and 81% specificity for neoplastic polyps. The accuracy and sensitivity were significantly lower than those that used the capillary pattern in OBI (accuracy 87% and sensitivity 93%) and the pit pattern in chromoendoscopy (accuracy 86% and sensitivity 90%). There were no significant differences in specificity (OBI 70% and chromoendoscopy 74%). The kappa analysis indicated good agreement in both OBI and chromoendoscopy. CONCLUSIONS: Capillary-pattern diagnosis in OBI is superior to that in conventional endoscopy and is not significantly different from pit-pattern diagnosis for predicting the histology of small colorectal polyps.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) occasionally induce small-bowel injury. However, the clinical features have only been partially clarified. The aim of this study was to clarify the clinical features of the disease and evaluate the effectiveness of endoscopic balloon dilation therapy for diaphragm disease, using double-balloon endoscopy (DBE). METHODS: This is a retrospective case study using our DBE database. Our inclusion criteria required patients to meet all the following criteria: (1) history of NSAID use; (2) endoscopic findings of erosion and/or ulcer and/or typical diaphragm-like strictures; (3) improvement in clinical findings (signs and symptoms) and/or endoscopic findings by cessation of NSAIDs, except for diaphragm disease; and (4) exclusion of other causes (e.g., malignant tumor, inflammatory bowel disease, and infectious disease). The clinical records of patients were investigated. RESULTS: Eighteen patients were included. Sixteen patients showed ulcerative lesions, and the remaining 2 patients showed diaphragm diseases. For localized lesions, 12 patients evidenced lesions in the ileum, 5 patients had lesions in the duodenum and/or jejunum, and 1 had lesions in both intestines. The ulcerative lesions were multiple with various morphologies that were located unrelated to mesenteric or antimesenteric sides. The endoscopic balloon dilations were performed safely, and all patients improved with regard to their symptoms. CONCLUSIONS: Symptomatic NSAID-induced small-bowel injuries exhibit a variety of patterns of ulcerative lesions as observed in the ileum in many cases. The endoscopic balloon dilation appears to be a safe and effective treatment for diaphragm disease.

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.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease, and thus is a major worldwide public health problem. Recently, an estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation for Japanese patients was proposed by the Japanese Society of Nephrology. However, the role of eGFR in the assessment of atherosclerosis is not well understood in Japanese patients. We analyzed the relationship between eGFR and severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 647 adult Japanese patients. baPWV correlated significantly and positively with age, hypertension, diabetes, prior cardiovascular disease, blood pressure, pulse pressure and heart rate, and negatively with eGFR (r=-0.405, p<0.0001). A multiple regression analysis revealed that baPWV correlated independently with eGFR. Furthermore, there was a stepwise increase in baPWV, corresponding to advances in CKD through stages 1 to 5. When CKD stage 3 was divided at eGFR 45 mL/min/1.73 m2, the baPWV of stage 3b (eGFR 30 to 44) was significantly higher than that of stage 3a (eGFR 45 to 59) independent of traditional risk factors, suggesting that an eGFR of 45 mL/min/1.73 m2 may be a critical cut off value to predict arterial stiffness in CKD. In conclusion, the newly proposed eGFR is significantly associated with arterial stiffness, independent of traditional risk factors for cardiovascular disease.

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.

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.

The small intestine is one of the most difficult organs in the gastrointestinal tract for performing endoscopy, and the method of enteroscopy so far has never been satisfactory. However, two new methods, capsule endoscopy and double-balloon endoscopy, have recently been developed to observe the entire small intestine, which is leading us to a new era for enteroscopy. The double-balloon endoscope is an electronic endoscope system developed by Fujinon based on the double-balloon method, a new endoscope insertion method devised by us. It enabled endoscopy even in the distal small intestine. The most remarkable characteristics of the double-balloon endoscope are its excellent ability to reach into deep portions of the small intestine while shortening and holding the intestine and its excellent controllability resulted from stabilizing the intestine by holding with balloons. It has been demonstrated that the double-balloon endoscope can be inserted deep into the small intestine either per os or per anum, and it has been reported that endoscopic diagnosis and treatment in the entire small intestine without general anesthesia have become possible. According to reports to date, the device boasts an excellent safety record with low incidence of complications, and its utility in the diagnosis and treatment of bleeding, tumor, stenosis, and polyposis in the small intestine has been demonstrated. Double-balloon endoscopy may become a standard procedure of enteroscopy, replacing conventional push enteroscopy and intraoperative enteroscopy. Double-balloon endoscopy is expected to play an important role in the management of small intestinal diseases together with capsule 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.

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.

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.

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.