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Rie Miyaki,
Shigeto Yoshida,
Shinji Tanaka,
Yoko Kominami,
Yoji Sanomura,
Taiji Matsuo,
Shiro Oka,
Bisser Raytchev,
Toru Tamaki,
Tetsushi Koide,
Kazufumi Kaneda, Masaharu Yoshihara,
Kazuaki Chayama
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ABSTRACT: BACKGROUND AND AIM: Magnifying endoscopy with flexible spectral imaging color enhancement (FICE) is clinically useful in diagnosing gastric cancer and determining treatment options. There is a learning curve, however. Accurate FICE-based diagnosis requires training and experience. In addition, objectivity is necessary. Thus, we developed a software program that can identify gastric cancer quantitatively. METHODS: We applied a bag-of-features framework with densely sampled scale-invariant feature transform (SIFT) descriptors to magnifying endoscopy images of 46 mucosal gastric cancers. We compared our computer-based findings to histologic findings. We calculated the probability of gastric cancer by means of logistic regression and determined sensitivity and specificity of our system. RESULTS: The average probability was 0.78±0.25 for the images of cancer and 0.31±0.25 for the images of noncancer tissue, with a significant difference between the two groups. An optimal cut-off point of 0.59 was determined on the basis of the ROC curves. The computer-aided diagnosis system yielded a detection accuracy of 85.9% (79/92), sensitivity for a diagnosis of cancer of 84.8% (39/46), and specificity of 87.0% (40/46). CONCLUSION: Further development of our system will allow for quantitative evaluation of mucosal gastric cancers on magnifying gastrointestinal endoscopy images obtained with FICE.
Journal of Gastroenterology and Hepatology 02/2013; · 2.87 Impact Factor
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ABSTRACT: BACKGROUND AND AIM: Gastrin is a growth factor for the gastric epithelial cells. However, it is unknown how gastric receptor (GR) expression is regulated in the gastric mucosa. We studied GR expression using a newly raised antibody and investigated the relationship between GR expression and gastritis. METHODS: Gastric receptor expression in 63 human gastric mucosa was studied. Helicobacter pylori infection and histological gastritis status were evaluated in gastric biopsy samples. In gastric ulcer cases, additional biopsy specimens were taken from injured mucosa. Fasting sera were collected and serum gastrin level evaluated. MKN-28 cells were cultured at various pH conditions, and the change in GR expression was determined. RESULTS: Gastric receptor expression was detected in the foveolar epithelium of the gastric mucosa, and its expression was stronger in patients infected with H. pylori. In particular, higher expression was detected in regenerating injured mucosa. There was no association between gastritis score/serum gastrin level and GR expression in H. pylori-positive cases. In MKN-28 cells, GR protein expression was lower in neutral conditions than in acidic or alkaline conditions. CONCLUSION: Gastric mucosal injury with H. pylori infection destroys the pH barrier on the foveolar epithelium and may induce GR expression through pH changes.
Digestive Diseases and Sciences 10/2012; · 2.12 Impact Factor
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ABSTRACT: BACKGROUND: Endoscopic detection of superficial squamous epithelial lesions of the pharynx has increased. OBJECTIVE: To clarify the association between macroscopic and histologic characteristics of intraepithelial pharyngeal neoplasias, and to evaluate the effectiveness of endoscopic submucosal dissection (ESD) for their treatment. DESIGN: Retrospective analysis of the features of high-grade dysplasia or carcinoma in situ (HGD/CIS) versus low-grade dysplasia (LGD) and of ESD-based outcomes. SETTING: Endoscopy department at a university hospital. PATIENTS: Fifty-one patients with 66 lesions treated by ESD from November 2007 to March 2011. RESULTS: Primary hypopharyngeal lesions were significantly more frequent in HGD/CIS than in LGD (54.1% vs 20.7%, P = .011), and oropharyngeal lesions were significantly less frequent in HGD/CIS (45.9% vs 79.3%, P = .011). HGD/CIS lesions were significantly larger than LGD lesions (median 8 mm vs 4 mm, P < .01). Morphologically, type 0-IIa was significantly more frequent in HGD/CIS lesions than in LGD lesions (37.8% vs 3.4%, P < .001), and type 0-IIb was significantly less frequent in HGD/CIS lesions (59.5% vs 96.6%, P < .001). The type IV intraepithelial papillary capillary loop pattern was significantly less frequent in HGD/CIS lesions than in LGD lesions (27.0% vs 55.2%, P = .025), and type V-2 was significantly more frequent in HGD/CIS lesions (18.9% vs 0%, P = .015). The en bloc resection rate was 97%. No serious complications occurred. There were no recurrent or metachronous tumors in the 41 patients followed for more than 1 year (median follow-up 27 months). LIMITATIONS: Retrospective design and single-center study. CONCLUSIONS: HGD/CIS and LGD differ in various clinical features. ESD appears to be an effective treatment for pharyngeal intraepithelial neoplasias.
Gastrointestinal endoscopy 09/2012; · 6.71 Impact Factor
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ABSTRACT: BACKGROUND: Bile acid and Helicobacter pylori (H. pylori) are important toxic factors for gastric mucosal injury. We examined the role of bile acid in promoting histologic gastritis and gastric carcinoma in Japanese patients.METHODS: A total of 767 patients (452 men, mean age 51.1 years) were studied. Gastric juice was collected by gastro-endoscopic examination, and the bile acid concentration was examined by enzymatic method. The grade of histologic gastritis was evaluated by gastric biopsies, and the relationship between the bile acid concentration and the gastritis score was examined. The occurrence of gastric cancer was examined by a retrospective cohort study. CDX2/CINC1 expression in RGM-1 cells was evaluated by real-time PCR.RESULTS: In H. pylori-positive patients, we found significant positive correlation between the bile acid concentration and the grades of atrophy/intestinal metaplasia (P < 0.01). However, we found significant negative associations between the bile acid concentrations and the histologic scores of mononuclear cell/neutrophil infiltrations (P < 0.01). Patients with a high concentration of bile acid developed gastric cancer more frequently than those with a low concentration (P < 0.05). Cholic acid treatment significantly increased CDX2 expression in RGM-1 cells. CINC1 expression in RGM-1 cell was significantly induced by coculture with H. pylori, and the induction was reduced by glycochenodeoxycholic acid treatment.CONCLUSION: The bile acid in gastric juice contributes to the progression of histologic atrophy and intestinal metaplasia without inflammatory cell infiltration, followed by carcinogenesis in H. pylori-positive patients.Impact: Bile acid promotes intestinal metaplasia and gastric carcinogenesis without inflammatory cell infiltration. Cancer Epidemiol Biomarkers Prev; 21(11); 1-7. ©2012 AACR.
Cancer Epidemiology Biomarkers & Prevention 09/2012; · 4.12 Impact Factor
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Digestive Diseases and Sciences 04/2012; 50(1):163-166. · 2.12 Impact Factor
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Toshiko Onitake,
Yoshitaka Ueno,
Shinji Tanaka,
Rie Hanaoka,
Kyoko Yoshioka,
Tsuyoshi Hatakeyama,
Shiro Oka,
Shigeto Yoshida,
Toru Hiyama,
Masanori Ito,
Yasuhiko Kitadai, Masaharu Yoshihara,
Kazuaki Chayama
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ABSTRACT: Cheilitis granulomatosa (CG) is a rare disease, which presents usually as a persistent swelling of the soft tissues in the
orofacial region and is characterized histologically by a granulomatous inflammation. We report the case of a 19-year-old
man who suffered from anal fistula. The patient had a 6-year history of asymptomatic and persistent swelling of the lower
lip. Examinations for gastrointestinal lesions containing double-balloon total enteroscopy revealed erosions located longitudinally
throughout the small intestine and the patient was diagnosed Crohn’s disease (CD). Biopsy of the lower lip showed non-caseating
granuloma and confirmed the diagnosis of CG. Despite an elemental diet and mesalazine therapy, the lip swelling persisted.
The CG can be the first presenting symptom of CD. CG as a complication of CD is discussed.
Clinical Journal of Gastroenterology 04/2012; 2(3):190-193.
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The American Journal of Gastroenterology 01/2012; 107(1):143-4. · 7.28 Impact Factor
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Yoshito Takemura,
Shigeto Yoshida,
Shinji Tanaka,
Rie Kawase,
Keiichi Onji,
Shiro Oka,
Toru Tamaki,
Bisser Raytchev,
Kazufumi Kaneda, Masaharu Yoshihara,
Kazuaki Chayama
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ABSTRACT: Narrow-band imaging (NBI) classification of colorectal lesions is clinically useful in determining treatment options for colorectal tumors. There is a learning curve, however. Accurate NBI-based diagnosis requires training and experience. In addition, objective diagnosis is necessary. Thus, we developed a computerized system to automatically classify NBI magnifying colonoscopic images.
To evaluate the utility and limitations of our automated NBI classification system.
Retrospective study.
Department of endoscopy, university hospital.
Performance of our computer-based system for classification of NBI magnifying colonoscopy images in comparison to classification by two experienced endoscopists and to histologic findings.
For the 371 colorectal lesions depicted on validation images, the computer-aided classification system yielded a detection accuracy of 97.8% (363/371); sensitivity and specificity of types B-C3 lesions for a diagnosis of neoplastic lesion were 97.8% (317/324) and 97.9% (46/47), respectively. Diagnostic concordance between the computer-aided classification system and the two experienced endoscopists was 98.7% (366/371), with no significant difference between methods.
Retrospective, single-center in this initial report.
Our new computer-aided system is reliable for predicting the histology of colorectal tumors by using NBI magnifying colonoscopy.
Gastrointestinal endoscopy 01/2012; 75(1):179-85. · 6.71 Impact Factor
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American journal of infection control 12/2011; 40(1):80. · 3.01 Impact Factor
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ABSTRACT: The true prevalence of Helicobacter pylori-negative gastric cancer (HpNGC) is unknown. We attempt to clarify the prevalence and clinicopathologic features of HpNGC in Japanese.
Helicobacter pylori infection was detected by antibody titer and microscopic observation. In addition, we confirmed the lack of endoscopic atrophy and histologic gastritis. In these cases, we added urea breath test or rapid urease test to confirm the absence of H. pylori. The mucus phenotype of gastric cancer tissue was also evaluated by immunohistochemistry.
We screened 3161 gastric cancer cases from 1996 to 2010, and 21 cases were regarded as H. pylori negative. Clinically, patients with HpNGC were younger than patients with H. pylori-positive gastric cancer (controls), and revealed a lack of male dominancy. Histologically, diffuse type was frequently found. All patients examined were pepsinogen negative. Among HpNGC cases with endoscopic resection, the depressed macroscopic appearance was dominant. The prevalence of HpNGC was calculated as 0.66% (95% confidence interval = 0.41-1.01). The mucus phenotype of HpNGC was similar to that of the controls.
The prevalence of HpNGC is very low and its pathological characteristics are different from common gastric cancer.
Helicobacter 12/2011; 16(6):415-9. · 3.15 Impact Factor
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Keiichi Onji,
Shigeto Yoshida,
Shinji Tanaka,
Rie Kawase,
Yoshito Takemura,
Shiro Oka,
Toru Tamaki,
Bisser Raytchev,
Kazufumi Kaneda, Masaharu Yoshihara,
Kazuaki Chayama
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ABSTRACT: Various surface mucosal pit patterns, as recognized by endoscopists, correlate with the histologic features of colorectal cancers. We investigated whether magnified endoscopy images of these pit patterns could be analyzed quantitatively and thus facilitate computer-aided diagnosis of colorectal lesions.
We applied both texture analysis and scale-invariant feature transform (SIFT) descriptors and discriminant analysis to magnified endoscopy images of 165 neoplastic colorectal lesions (pit patterns: type III(L)/IV, n = 44; type V(I)-mildly irregular, n = 36; type V(I)-severely irregular, n = 45; type V(N), n = 40) [histologic findings: tubular adenoma (TA), n = 56; carcinoma with intramucosal or even scant submucosal invasion (M/SM-s), n = 52, carcinoma with massive submucosal invasion (SM-m), n = 57]. We analyzed differences in pit pattern values and corresponding histologic values to determine whether the values were diagnostically meaningful.
Gray-level difference matrix (GLDM) inverse difference moment and spatial gray-level dependence matrix (SGLDM) local homogeneity values differed significantly between type III(L)/IV and type V(N) pit patterns. Values differed significantly for each analyzed feature between type III(L)/IV and type V(I)-severely irregular patterns and were high but descending for type III(L)/IV, type V(I)-mildly irregular, and type V(I)-severely irregular pit patterns (in that order). Similarly, texture analysis yielded high but descending values for TA, M/SM-s, and SM-m (in that order). Furthermore, SIFT descriptors and discriminant analysis yielded differences that were superior to those obtained by texture analyses.
Computer analysis of magnified endoscopy images for the diagnosis of colorectal lesions appears feasible. We anticipate further developments in the computer-aided diagnosis of pit patterns on magnified endoscopy images.
Journal of Gastroenterology 09/2011; 46(12):1382-90. · 4.16 Impact Factor
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ABSTRACT: Serum screening systems are beneficial for gastric cancer mass surveys; however, the marker for diffuse type gastric cancer (DGC) is not defined. We attempted to define the high-risk group for DGC by using serum markers of anti-Helicobacter pylori antibody and pepsinogens (PG).
Forty-two patients in the early stage of DGC and 511 controls were enrolled. Fasting serum samples were collected, and anti-H. pylori antibody and PG were evaluated. The risk for DGC was calculated.
The prevalence of DGC was higher in H. pylori-positive patients (odds ratio [OR] = 4.3 in men, 9.6 in women). DGC prevalence was significantly higher in the PG1+ group in women (OR = 10.7); however, it was lower in the PG3+ group in both men and women. Patients with PG II ≥ 30 revealed a significantly higher risk for DGC. By combining factors, higher OR (OR = 12.5 in men, 42.7 in women) were obtained when we defined the risk group as H. pylori-positive, PG-negative, and having PG II ≥ 30.
The risk group for DGC can be defined by evaluating ordinary serum gastritis markers.
Journal of Gastroenterology and Hepatology 08/2011; 27(3):598-602. · 2.87 Impact Factor
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ABSTRACT: Serrated adenomas (SAs), recently subdivided into traditional SAs (TSAs) and sessile SAs (SSAs), are recognized as a distinct form of neoplasia of the colorectum. One of the characteristics of SAs is hypermaturation of the gland epithelium due to the low extent of cell loss by apoptosis. Mutations of mitochondrial DNA (mtDNA) are closely associated with abnormality in apoptosis. We therefore examined mtDNA mutations in colorectal lesions including hyperplastic polyps (HPs), SSAs, TSAs, and carcinomas.
Examined were 25 HPs, 32 SSAs, 19 TSAs, and 138 carcinomas. The D310 region of the mtDNAs was examined by microsatellite assay.
mtDNA mutations were detected in none of 25 (0%) HPs, one of 32 (3%) SSAs, six of 19 (32%) TSAs, and eleven of 133 (8%) carcinomas (five of the 138 carcinomas were not informative). The frequency of mtDNA mutations in the TSAs was significantly higher than that in the HPs, SSAs, and carcinomas (P = 0.004, P = 0.008, and P = 0.009, respectively). The frequency of mtDNA mutations in carcinomas was not significantly higher than that in HPs and SSAs (P = 0.14 and P = 0.28, respectively).
Our data suggest that mtDNA mutations may play an important role in the development of TSAs and could be used as a genetic marker to aid in the diagnosis of colorectal lesions.
Journal of Gastroenterology and Hepatology 06/2011; 26(10):1565-9. · 2.87 Impact Factor
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ABSTRACT: To determine whether contrast-enhanced ultrasonography (CEUS) can be used to discriminate between colon cancer and acute inflammation, and between mucinous and non-mucinous carcinoma.
CEUS (with perflubutane microbubbles) was performed in two study groups: colon cancer (n = 34) and acute inflammation (n = 14). For evaluation, the microvascular structure was classified as irregular or regular, and vessel diameter was classified as ≥2 mm or <2 mm. Tumor enhancement was classified as homogeneous, heterogeneous (obvious defect), or hypoenhancement. Moreover, the defect area was classified according to the presence or absence of vessels. Differences in imaging features between the two groups or between types of tumors were examined statistically.
The vascular structure was irregular in 76.5% of colon cancers but only 28.6% of acute inflammations (P < 0.01). A significantly greater number of cancers contained vessels ≥2 mm (70.6% vs. 7.1%) (P < 0.001). Both abnormalities were found in 58.8% of colon cancers but in none of the acute inflammations. Enhancement patterns differed between tumor types, with mucin pools being readily identifiable.
Differentiation between colon cancer and acute inflammation is possible with CEUS. Furthermore, prediction of mucinous vs. non-mucinous adenocarcinoma is possible.
Abdominal Imaging 04/2011; 37(2):297-303. · 1.73 Impact Factor
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ABSTRACT: To examine the frequency and prevention of musculoskeletal pain in Japanese gastrointestinal endoscopists and non-endoscopist physicians.
Questionnaires were sent to 275 endoscopists and 173 non-endoscopists working in Hiroshima University Hospital and its affiliated hospitals.
The completed questionnaires were returned by 190 (69%) endoscopists and 120 (69%) non-endoscopists. The frequency of pain in the hand and wrist, and especially the left thumb, was significantly higher in endoscopists than in non-endoscopists (17% vs 6%, P = 0.004). Using multivariate analysis, the only significant factor associated with this pain was the age of the endoscopist (odds ratio 2.77, 95% confidence interval, 1.23-6.71, P = 0.018). Interestingly, endoscopists had made significantly fewer modifications to their endoscopic practices than non-endoscopists (12% vs 33%, P < 0.0001) to prevent pain.
Pain in the hand and wrist may be endoscopy-related. However, endoscopists made little modifications in practice to prevent such pain. More attention to prevention appears necessary.
World Journal of Gastroenterology 03/2011; 17(11):1488-93. · 2.47 Impact Factor
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ABSTRACT: In the treatment of superficial esophageal tumors (SET), en bloc histologically-complete resection reduces the risk of local recurrence. Endoscopic oblique aspiration mucosectomy (EOAM) and endoscopic submucosal dissection (ESD) have been applied to resect SET. The aim of this study was to retrospectively determine whether ESD is more advantageous than EOAM for SET.
In the present study, there was a total of 122 patients in whom 162 SET were resected endoscopically at Hiroshima University Hospital. EOAM (83 lesions/63 patients) or ESD (79 lesions/59 patients) was performed. En bloc histologically-complete resection rates, operation time, complications, and the local recurrence rate were studied.
In SET > 20 mm, the en bloc histologically-complete resection rate was significantly higher with ESD than with EOAM (94% vs 42%, P < 0.001). In SET of 16-20 mm, the rate tended to be higher with ESD than with EOAM (100% vs 81%, P = 0.08). In SET < 15 mm, the rates did not differ significantly between groups. The average operation time was significantly longer for ESD than for EOAM, regardless of tumor size (49.7 ± 33.0 min vs 19.1 ± 6.1 min, P < 0.001). Complication rates did not differ significantly between groups. The local recurrence rate was significantly lower with ESD than with EOAM (0%, mean observation period: 18.9 months vs 9%, mean observation period: 30.7 months, P = 0.03).
Although increased operation time with ESD remains problematic, SET > 15 mm should be treated with ESD to reduce local recurrence. In lesions ≤ 15 mm, EOAM might be preferable, especially in high-risk patients.
Journal of Gastroenterology and Hepatology 02/2011; 26(2):275-80. · 2.87 Impact Factor
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ABSTRACT: Whether multiple esophageal squamous cell carcinomas (SCCs) in a patient develop through an identical genetic pathway is still unclear. We examined multiple esophageal SCCs for alterations of p53, p16, IRF and mitochondrial DNA (mtDNA) and microsatellite instability (MSI). Thirty patients with multiple superficial esophageal SCCs, 23 with double lesions and 7 with triple lesions, were enrolled. Loss of heterozygosity (LOH) of p53 (TP53), p16 (D9S171), IRF (IRF) and other microsatellite loci including D1S191, D17S858, D18S58 and D18S61 of the tumors was examined by microsatellite assay. Mutations of p16 and mtDNA were examined with PCR single-strand conformation polymorphism (SSCP) analysis. LOH of p53, p16 and IRF were detected in 16 of 50 (32%), 5 of 38 (13%) and 5 of 48 (10%) tumors, respectively. Mutations of p16 were detected in 4 of 67 (6%) tumors. Six of 67 (9%) tumors had mtDNA alterations and none of the tumors showed high-frequency MSI. All 30 patients showed one or more gene alterations in one or more genetic loci. Discordant genetic patterns among individual lesions within a patient were observed in 28 of the 30 (93%) patients. The most discordant locus was TP53, present in 11 of 29 (38%) informative cases, followed by D18S61, present in 11 of 30 (37%) informative cases. These results suggest that the genetic pathways of multiple esophageal SCCs may differ even within the same patient.
Oncology Reports 02/2011; 25(2):453-9. · 1.84 Impact Factor
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ABSTRACT: Few reports have described the cancer prevalence of peptic ulcer patients with long-term follow-up studies. We have conducted a long-term retrospective cohort study of Japanese peptic ulcer patients and evaluated the risk factors for the occurrence of gastric cancer (GCa). A total of 136 patients diagnosed with peptic ulcers from 1975 to 1983 were enrolled. These 136 cases [102 males and 34 females; 69 gastric ulcer (GU) and 67 duodenal ulcer (DU) patients at the time of enrollment; mean follow-up period of 14.4 years (range 1-30 years)] after being matched with a tumour registry database in Hiroshima prefecture were surveyed for GCa. We investigated Helicobacter pylori duodenal ulcer promoter gene A (dupA) using paraffin-embedded gastric biopsy specimens in 56 cases. Gastric acid secretion and basal acid output (BAO) in 40 cases, and maximal acid output in 68 cases, had been measured at first diagnosis of peptic ulcers. GCa was detected in 24 patients (17 with GU, 7 with DU) during the follow-up. The prevalence of GCa was significantly higher in GU patients than in DU patients (log-rank test P<0.05). dupA-positive H. pylori was detected not only in DU patients (9/20) but also in GU patients (9/36). Gastric acid output was significantly larger in quantity in patients with dupA-positive H. pylori than in those with dupA-negative H. pylori (P<0.05). The occurrence of GCa was significantly lower in patients with dupA-positive H. pylori and a high BAO level (log-rank test P<0.05). DUs, higher acid output and dupA-positive H. pylori were negatively associated with GCa.
Journal of Medical Microbiology 12/2010; 59(Pt 12):1484-9. · 2.50 Impact Factor
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ABSTRACT: Because pit pattern classification of colorectal lesions is clinically useful in determining treatment options for colorectal tumors but requires extensive training, we developed a computerized system to automatically quantify and thus classify pit patterns depicted on magnifying endoscopy images.
To evaluate the utility and limitations of our automated pit pattern classification system.
Retrospective study.
Department of endoscopy at a university hospital.
Performance of our automated computer-based system for classification of pit patterns on magnifying endoscopic images in comparison to classification by diagnosis of the 134 regular pit pattern images by an endoscopist.
For type I and II pit patterns, the results of discriminant analysis were in complete agreement with the endoscopic diagnoses. Type IIIl was diagnosed in 29 of 30 cases (96.7%) and type IV was diagnosed in 1 case. Twenty-nine of 30 cases (96.7%) were diagnosed as type IV pit pattern. The overall accuracy of our computerized recognition system was 132 of 134 (98.5%).
Our system is best characterized as semiautomated but is a step toward the development of a fully automated system to assist in the diagnosis of colorectal lesions based on classification of pit patterns.
Gastrointestinal endoscopy 11/2010; 72(5):1047-51. · 6.71 Impact Factor
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ABSTRACT: Colorectal endoscopic submucosal dissection (ESD) is a difficult procedure. We aimed to retrospectively assess the relationship between the outcome of ESD for colorectal tumors and the degree of fibrosis.
We examined 203 consecutive patients with colorectal tumors larger than 20 mm in diameter who had undergone ESD at our hospital from November 2002 to June 2009. During ESD, the degree of submucosal fibrosis was classified into three types (F0-2). The relationship between the degree of fibrosis and the lesion characteristics and those between the outcome of ESD and the degree of fibrosis were analyzed.
In the cases of granular laterally spreading tumors, the incidence of F2 fibrosis in nodular mixed-type tumors was significantly higher than that in homogenous-type tumors. An increase in the experience of the operators caused significant improvements in the rates of complete en bloc resection (p = 0.022) and perforation (p = 0.03) in the cases of lesions with F0-1 fibrosis. By contrast, operator experience did not cause any significant improvements in the rates of complete en bloc resection and perforation in the cases of lesions with F2 fibrosis.
Experienced operators could safely perform complete en bloc resection in the cases of lesions with F0-1 fibrosis. However, in the cases of lesions with F2 fibrosis, the rate of complete en bloc resection was low and the perforation rate was high even when ESD was performed by an experienced operator.
Scandinavian journal of gastroenterology 11/2010; 45(11):1329-37. · 2.08 Impact Factor
