[show abstract][hide abstract] ABSTRACT: MUC2 is the primary component of the mucin barrier that separates the intestinal microbiota and the intestinal epithelium. This mucous barrier is affected by both luminal/microbial factors and host/immune factors, both of which have genetic and environmental determinants. The complex interactions between these players in health and disease states are not fully understood. Inflammatory bowel disease (IBD) has both genetic and environmental etiologies that lead to the breakdown of the epithelial barrier. In this review, we explore the up-to-date evidence that implicates mucin in the pathogenesis of IBD. In IBD, quantitative changes in mucin secretion occur, as well as structural changes in mucin's glycoprotein core and the sulfation and sialylation of mucin's oligosaccharide residues. These changes are associated with a diminished functionality of the mucous barrier. We identify the various genetic mutations associated with these changes and outline the animal models that have enhanced the current understanding of the genetic basis for IBD. Further study is needed to better characterize the immune and genetic influences on mucin expression and secretion and role of endoplasmic reticulum stress and a defective unfolded protein response in mediating these changes.
Journal of clinical gastroenterology 11/2012; · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the pattern of secreted mucin expression in Helicobacter pylori (H. pylori)-related, nonsteroidal anti-inflammatory drug (NSAID)-related and idiopathic gastric ulcers.
We randomly selected 92 patients with H. pylori-associated (n = 30), NSAID-associated (n = 18), combined H. pylori and NSAID-associated gastric ulcers (n = 24), and patients with idiopathic gastric ulcers (n = 20). Immunohistochemistry for T-cell CD4/CD8, and for mucin 5AC (MUC5AC) and mucin 6 (MUC6), was performed on sections of the mucosa from the ulcer margin. Inflammation score was assessed according to the Sydney system.
MUC5AC was expressed on the surface epithelium (98.9%) and neck glands (98.9%) with minimal expression in the deep glands (6.5%). MUC6 was strongly expressed in the deep glands (97.8%), variable in the neck glands (19.6%) and absent in the surface epithelium (0%). The pattern of mucin expression in idiopathic ulcer margins was not different from the expression in ulcers associated with H. pylori, NSAIDs, or combined H. pylori and NSAIDs. CD4/CD8 ratio was higher in H. pylori-positive patients (P = 0.009). Idiopathic ulcers are associated with hospitalized patients and have higher bleeding and mortality rates.
Idiopathic ulcers have a unique clinical profile. Gastric mucin expression in idiopathic gastric ulcers is unchanged compared with H. pylori and/or NSAID-associated ulcers.
World Journal of Gastroenterology 09/2012; 18(33):4597-603. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: The ratio of Helicobacter pylori/NSAID-negative gastric ulcers is increasing. Idiopathic gastric ulcers have unique clinical and endoscopic features, and are associated with more bleeding complications and a higher mortality. Alterations in gastric mucin expression and sialylation pattern may be important in ulcer pathogenesis.
The purpose of this study was to determine the expression pattern of membrane-bound mucins and side chain sugars in H. pylori associated-, NSAID-, and idiopathic-gastric ulcers.
We randomly selected 92 patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for T-cell CD4/CD8, MUC1, MUC4, MUC17, and ECA and SNA lectins staining was performed on sections from the ulcer margins. Inflammation score was assessed according to the Sydney system.
Bleeding and mortality rates were significantly higher in group 4. CD4 positive T cell count was higher in H. pylori positive patients (P = 0.009). Staining intensity of MUC17 was higher in group 1 than in group 4, foveola and glands alike, with 11.50 ± 3.47 versus 6.80 ± 4.02, and 9.61 ± 4.26 versus 7.59 ± 3.26, respectively (P < 0.0001). This was a mirror image with MUC1. SNA lectin staining was increased in group 4, in parallel to MUC1 expression, indicating more abundant α2-6 sialylation in that group.
Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was demonstrated for MUC1. This observation might be important, since different mucins with altered sialylation patterns likely differ in their protection efficiency against acid and pepsin.
Digestive Diseases and Sciences 05/2012; 57(10):2535-44. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Colonoscopy of asymptomatic, healthy individuals for colorectal cancer screening rarely causes complications and adverse events. Thus, quality of life (QOL) of the participants should not be affected by the procedure.
The aim of the study was to isolate the influence of colonoscopy, by investigation QOL before and after the procedure in a cohort of consecutive patients with different indications.
This study is a prospective, longitudinal study, designed to compare the potential influence of colonoscopy on QOL. For a cohort of consecutive patients undergoing colonoscopy for various reasons and indications, we filled a QOL short form-36 and a short feedback questionnaire before, immediately after, and a month after the procedure. We also measured the quality of the endoscopy, the outcome in patients, and acceptability among patients.
There was no significant change before and immediately after colonoscopy in any of the short form-36 parameters. Physical functioning, role limitation physical, pain, general health, vitality, social functioning, role limitation mental, and mental health had very similar scores before and 2-3 h after the procedure. There was a decrease in the physical functioning a month after the procedure (P=0.01). The same was found for non-inflammatory bowel disease patients, but not for inflammatory bowel disease patients.
Colonoscopy did not affect QOL in the short or the long duration after the procedure. As such, colonoscopy may be suitable as a part of screening programs. We believe that QOL estimation should be an integral part of assessment of a screening program.
European journal of gastroenterology & hepatology 03/2012; 24(7):781-6. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Fecal immunochemical test (FIT) is gaining popularity as a screening tool for colorectal cancer. The introduction of capsule endoscopy (CE) enables an assessment of the relationship between small bowel (SB) lesions and FIT results.
To determine whether SB lesions found by CE are associated with an increased rate of positive FIT.
Consecutive patients undergoing CE for obscure occult gastrointestinal bleeding also underwent FIT. CE was performed using the PillCam SB and FIT was performed with OC-Micro (three samples, threshold 75 and 100 ng/ml).
Fifty-one patients were included; the mean lowest hemoglobin was 9.1 ± 2.1 g/dl. Twenty-six patients (51.0%) had SB lesions identified by CE and were classified as the probable or suspected source of bleeding. At the threshold of 75 and 100 ng/ml, 12 of 26 (46.1%) and 10 of 26 (38.4%), respectively had a positive FIT. In contrast, only two of 25 (8.0%) patients without SB lesions had a positive FIT at both thresholds (P=0.002 and 0.010 respectively). The mean fecal hemoglobin in patients with SB lesions classified as probable or suspected source of bleeding versus patients with normal SB was 345.6 ± 773 and 25.0 ± 37.7 ng/ml, respectively (P=0.025).
A positive FIT can be explained by significant SB lesions detected by CE. Further studies are still needed to evaluate whether asymptomatic patients with positive FIT and nonexplanatory colonoscopy should undergo further study of the SB.
European journal of gastroenterology & hepatology 11/2011; 23(11):1024-8. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: JC virus (JCV) may infect the gastrointestinal tract in childhood, and, by encoding a gene for T-antigen (T Ag), can initiate chromosomal instability in epithelial cells.
We looked for JCV DNA in the cancer tissue of patients with sporadic colorectal cancer (CRC, Group A) and with positive family history and Bethesda criteria (Group B). We hypothesized that the role of JCV may be different between these two groups.
Fifty-six patients were randomly selected from our database, 30 in Group A and 26 in Group B. DNA was isolated from the tumor, normal mucosa, and plasma, and JCV DNA sequences were looked for with specific polymerase chain reaction (PCR) assays for T Ag primers. Immunohistochemistry for hMLH1, hMSH2, hMSH6, and PMS2 was performed on paraffin-embedded tissue.
In Group A, T Ag was demonstrated in 6 (20.00%) and 3 (10.00%) of the tumors and adjacent normal mucosa, respectively (P = 0.094). In Group B, the corresponding observations were 10 (38.46%) and 6 (23.07%), respectively (P < 0.001). Immunohistochemistry for hMLH1, hMSH2, hMSH6, and PMS2 was performed in all of the Group A and B patients. All patients of Group A (100%) showed expression of these proteins, while only 19 patients of Group B did so (73.1%), P = 0.009. JCV T Ag DNA was found in 20, 28.5, and 42.1% of the tumors in Group A, Group B with negative staining for DNA repair genes, and Group B with a positive staining, respectively (NS).
CRC patients with positive family history have a higher incidence of JCV T Ag, but this did not correlate with specific DNA repair gene mutations. We could not conclude that, on the background of genetic mutation in one of the DNA repair genes, JCV acts as the missing link in the chain of events leading to CRC.
Digestive Diseases and Sciences 08/2011; 57(1):79-84. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Approximately 30% of colorectal cancers exhibit familial clustering. Currently, we recognize a number of different types of polyps and polyposis syndromes that are classified according to the histology of the typical polyp. We differentiate between adenomas, hyperplastic, and hamartomatous polyps as well as between syndromes that are manifested by 10-100 or above 100 polyps. It is essential to distinguish between these syndromes as each has a different mode of presentation, spectrum of signs and symptoms and cancer risk associated with them. With the knowledge accumulating, we now have the tools to lower the risk of cancer by performing specific screening programs that are tailored to each syndrome. In these guidelines we focus on the non-adenomatous polyps, hyperplastic and hamartomatous polyposis syndromes. We outline the importance of multi-sector team work that includes the family practitioner, gastroenterologist, pathologist, genetic counselor, surgeon, and social worker.
[show abstract][hide abstract] ABSTRACT: Approximately 30% of colorectal cancers exhibit familial clustering. We recognize different types of polyps and polyposis syndromes that are classified according to the histological diagnosis. We differentiate between adenomas, hyperplastic, and hamartomatous polyps as well as between syndromes that are manifested by 10-100 or above 100 polyps. Only about 1% of colorectaL cancers (CRCs) are due to adenomatous polyposis syndrome. It is essential to distinguish between these syndromes as each has a different mode of presentation, spectrum of signs and symptoms and cancer risk. With the knowledge that is accumulating we now have the tools to lower the risk of cancer by performing specific screening programs that are tailored to each syndrome specifically. We present the Israeli guidelines for management of adenomatous polyposis, based on the American and European experience and consensus. We outline the importance of mutti-sectorial team work that includes the family practitioner, gastroenterologist, pathologist, genetic counselor, surgeon and social worker.
[show abstract][hide abstract] ABSTRACT: Immunochemical fecal occult blood test (FIT) is a new colorectal cancer (CRC) screening method already recommended by the American screening guidelines. We aimed to test the feasibility of FIT as compared to guaiac fecal occult blood test (G-FOBT) in a large urban population of Tel Aviv. Average-risk persons, aged 50-75 years, were offered FIT or G-FOBT after randomization according to the socioeconomic status of their clinics. Participants with positive tests underwent colonoscopy. Participants were followed through the Cancer Registry 2 years after the study. Hemoccult SENSA™ and OC-MICRO™ (three samples, 70 ng/ml threshold) were used. FIT was offered to 4,657 persons (Group A) and G-FOBT to 7,880 persons (Group B). Participation rate was 25.9% and 28.8% in Group A and B, respectively (p < 0.001). Positivity rate in Group A and B was 12.7% and 3.9%, respectively (p < 0.001). Cancer found in six (0.49%) and eight (0.35%) patients of Group A and B, respectively (NS). Cancer registry follow-up found missed cancer in five (0.22%) cases of Group B and none in Group A (NS). The sensitivity, specificity, negative and positive predictive value for cancer in Group A and B were 100%, 85.9%, 100%, 3.9% and 61.5%, 96.4%, 99.8%, 9.1%, respectively. There was increased detection of advanced adenomatous polyp (AAP) by FIT, irrespective of age, gender, and socioeconomic status (Per Protocol: odds ratio 2.69, 95% confidence interval 1.6-4.5; Intention to Screen: odds ratio 3.16, 95% confidence interval 1.8-5.4). FIT is feasible in urban, average-risk population, which significantly improved performance for detection of AAP and CRC, despite reduced participation.
International Journal of Cancer 05/2011; 128(10):2415-24. · 6.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Genetic background is suspected in about 20% of colorectal cancer (CRC) cases, in which either genetic polymorphisms or Mendelian heritable factors are involved. Currently known CRC syndromes include various polyposis syndromes (<1% of total CRC cases) and Lynch syndrome (LS), previously termed hereditary nonpolyposis colorectal cancer (HNPCC, comprises 3-5% of all CRC cases). LS is caused by dominantly inherited mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and results in a very high lifetime risk (approximately 80%) for CRC and significantly increased risk for extracolonic tumors in regions such as the endometrium, ovary, urinary tract, lymphoma, stomach, pancreas small bowel and brain. Carriers are advised to undergo specific medical and intense endoscopic surveillance. Diagnosis of carriers is mandatory for providing appropriate recommendations for surveillance, which was shown to decrease morbidity, mortality and health costs. Diagnosis of LS dictates preventive surgical procedures for the colon endometrium and ovaries, and assists in decisions regarding CRC chemotherapy. Family members' screening and surveillance is determined by mutation testing. Diagnosis is performed, based on the clinical selection criteria of Amsterdam and Bethesda and according to typical histology of tumor tissue. Initially, tumor testing is performed by either microsatellite instability (MSI), immunohistochemistry (IHC) or both. Certain Jewish ethnical subgroups may undergo founder mutation testing. Ultimate identification of the mutation by sequencing and MLPA is performed according to the IHC results. In families with hereditary CRC criteria, in which workup for LS is negative, the surveillance protocol will be determined by an experienced multidisciplinary team, including a formal genetic consultation.
[show abstract][hide abstract] ABSTRACT: Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA. Chromosomal instability (CIN) was established as the key mechanism in cancer development. Later, it was found that CRC results not only from the progressive accumulation of genetic alterations but also from epigenetic changes. JC virus (JCV) is a candidate etiologic factor in sporadic CRC. It may act by stabilizing β-catenin, facilitating its entrance to the cell nucleus, initialing proliferation and cancer development. Diploid CRC cell lines transfected with JCV-containing plasmids developed CIN. This result provides direct experimental evidence for the ability of JCV T-Ag to induce CIN in the genome of colonic epithelial cells. The association of CRC hMLH1 methylation and tumor positivity for JCV was recently documented. JC virus T-Ag DNA sequences were found in 77% of CRCs and are associated with promoter methylation of multiple genes. hMLH1 was methylated in 25 out of 80 CRC patients positive for T-Ag (31%) in comparison with only one out of 11 T-Ag negative cases (9%). Thus, JCV can mediate both CIN and aberrant methylation in CRC. Like other viruses, chronic infection with JCV may induce CRC by different mechanisms which should be further investigated. Thus, gene promoter methylation induced by JCV may be an important process in CRC and the polyp-carcinoma sequence.
[show abstract][hide abstract] ABSTRACT: This position paper of the Section of Gastrointestinal Oncology of the Israeli Gastroenterological Association recommends specific guidelines for colorectal cancer surveillance in patients with inflammatory bowel disease. Colorectal cancer (CRC) is a severe complication of inflammatory bowel disease (IBD), generally developing into a longstanding disease. The Lifetime prevalence of CRC in ulcerative colitis (UC) patients is estimated to be 2% after 10 years, 8% after 20 years, and even 18% after 30 years of extensive disease. Screening colonoscopy should be initiated 8-10 years after onset of symptoms in extensive UC patients (pancolitis), and after 15 years in patients with left-sided colitis (UC or Crohn's). Surveillance should continue periodically at an interval of every 1 to 2 years. Surveillance colonoscopies should be performed in combination with an extensive biopsy protocol. High-grade dysplasia (HGD) in flat mucosa or a dysplasia associated Lesion or mass (DALM) is considered an indication for colectomy when the pathological findings are confirmed by a second experienced pathologist. Further research is directed toward improving detection of dysplasia during colonoscopy through the use of novel endoscopic imaging techniques which are hoped to impact the approach to cancer prevention in patients with IBD.
[show abstract][hide abstract] ABSTRACT: Barret's esophagus (BE) is defined as a situation in which the distal esophageal squamous epithelium was replaced by columnar epithelium, with or without goblet cells. BE is considered a significant risk factor for the development of esophageal cancer, however, screening is recommended only for high risk patients. The new guidelines determine the proper terminology of the endoscopic appearance of BE and the way that biopsies should be taken. After BE is confirmed, surveillance is extremely important as its performance has been shown to prevent cancer and death. The surveillance is based on the endoscopic and pathological findings, highlighting the importance of advanced endoscopy and specialized pathology expertise. The guidelines determine the place of the endoscopic ablative technology and specialized surgery in these patients.
[show abstract][hide abstract] ABSTRACT: To compare the uptake of faecal immunochemical occult blood test (FIT) with guaiac faecal occult blood test (gFOBT) in a screening programme, with specific attention to the demographic and socioeconomic factors that might affect test uptake.
The Clalit Health Service screening programme, Israel.
Average-risk individuals aged 50-75 years were randomized into a FIT arm or gFOBT arm using a programme based on the socioeconomic status (SES) of their primary care clinics. G-FOBT was performed with Hemoccult SENSA™ (3 evacuations) and FIT with the OC- MICRO(TM) (3 evacuations, refrigerating mandated). The GLIMMIX model was used.
There were 5,464 and 10,668 eligible participants in the FIT and gFOBT arms respectively. Compliance in taking the kits was better (but not statistically significantly better) with gFOBT (37.8% vs. 29.3%; odds ratio [OR] 1.43 [95% CI 0.73-2.80]; P = 0.227). Kit return was higher in the FIT arm (65.0% vs. 78.9%; OR 0.45 [95% CI 0.24-0.83], P = 0.021). Overall test uptake was affected by age, gender, being immigrant and SES (determined by whether or not the participant paid national insurance tax, and the SES of the primary care clinic). The overall uptake of gFOBT and FIT was comparable (OR 0.996 [95% CI 0.46-2.17], P = 0.99).
Overall compliance for test uptake was comparable between the two methods despite the more demanding procedure in the FIT arm. Sociodemographic parameters were the major determinants of compliance. An educational programme, with emphasis on the sociodemographic characteristics of the target population, should be instigated.
Journal of Medical Screening 01/2011; 18(3):135-41. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with positive fecal occult blood test and unrevealing colonoscopy are often advised to undergo esophago-gastro-duodenoscopy (EGD) to exclude a bleeding source in the upper gastrointestinal tract. In this study, we evaluated EGD findings in patients with positive immunochemical fecal occult blood test (I-FOBT) not explained by colonoscopy.
Out of 1221 consecutive patients having total colonoscopy after preparing I-FOBT (OC-MICRO, with threshold of 75 or 100 ngHb/ml), we included only patients without colorectal cancer or advanced adenomatous polyp on colonoscopy, who also underwent EGD within 4 months of the fecal blood testing. Findings on EGD were classified as those lesions which are likely or unlikely to bleed.
EGD was performed in 160 patients after a negative colonoscopy. The procedure was performed 1.6 ± 1.4 months after the I-FOBT. Lesion with a bleeding potential was found in 24 patients (15%). In three (12.5%) and two (8.3%) of these patients I-FOBT was positive at the 75 and 100 ngHb/ml threshold, respectively. In 136 patients EGD was normal, and I-FOBT was similarly positive in 16 (11.7%) and 13 patients (9.5%), respectively. The mean fecal hemoglobin was also similar between the groups.
Immunological FOBT positivity was not correlated with the finding of lesions, which are likely to bleed on EGD. Thus, EGD is probably not indicated in patients with positive I-FOBT and unrevealing colonoscopy.
European journal of gastroenterology & hepatology 10/2010; 22(12):1431-4. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: The position paper of the GastrointestinaL Oncology Section of the Israeli Gastroenterological Association recommends specific guidelines for surveillance after polypectomy and curative resection of colorectal cancer. Periodic colonoscopy is necessary for early detection of metachronous lesions or cancer recurrence. After polypectomy of a simple hyperplasic polyp, colonoscopy is repeated in 10 years. Small adenoma dictates colonoscopy after 5-10 years. In the case of advanced adenoma, repeat coLonoscopy is to be conducted after 3 years. The personal impression of the colonoscopists may advance procedures to an earlier colonoscopy, especially after piecemeal polypectomy of a large sessile polyp. Fecal occult blood test or any other screening procedures are not needed after polypectomy. Colonoscopy, carcinoembrionic antigen examination (CEA) and liver imaging are necessary for surveillance after curative resection of colorectal cancer, and improve survival. Total colonoscopy should be performed before the operation or in cases with obstructive carcinoma, colonic imaging should be completed with virtual colonoscopy. Total colonoscopy should be performed 3-6 months after surgery if not conducted previously. The next follow-up is needed 3 and 5 years after the operation. After low anterior resection, the recurrence rate may be high and patients who have not undergone radiation therapy nor mesorectal resection should undergo sigmoidoscopy every 3-6 months for 2-3 years after surgery.
[show abstract][hide abstract] ABSTRACT: Hypermethylation of tumor suppressor genes' promoter and JC virus infection may be etiologic factors in the development of colorectal cancer (CRC).
To look at both JC virus T antigen and hMLH1 promoter methylation in CRC tissue in Israeli ethnic groups with different incidence of CRC.
Twenty-four consecutive patients with sporadic CRC were included in the study. Genomic DNA was isolated from paraffin-embedded microdomains removed from five slides of 7 mum by deparaffinizing in multiple xylene washes. Isolated DNA was used as a template for PCR to amplify DNA sequences coding the amino terminus of JC virus T antigen. Methylation-specific PCR was performed on bisulfite-modified DNA templates from CRC tissue materials to study methylation status of hMLH1 promoter, using two sets of primers specific for amplification of methylated and unmethylated alleles.
hMLH1 promoter methylation was observed in five patients (20.8%) who were also positive for JC virus T antigen, with even distribution among the ethnic groups. JC virus T antigen DNA was found in cancer tissues of 20 of the 24 patients; 50, 90.9, and 100% of Asia-Africa-born Jews, Europe-America-born Jews, and Israeli Arabs, respectively (P = 0.036 between the first group to the other).
Evidence for higher JC virus infection was shown among Europe-America-born Jews and Israeli Arabs. hMLH1 promoter methylation was evenly distributed between different ethnic groups in Israel.
European journal of gastroenterology & hepatology 08/2010; 22(8):938-41. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: JC virus (JCV) is thought to infect approximately 80% of the human population. Antibodies against JCV can be found in the sera of many people with and without colorectal carcinoma (CRC). We hypothesized that JCV antibody titer will be higher in CRC patients than in healthy controls.
To evaluate this hypothesis in a cohort of patients undergoing colonoscopy. We compared JCV antibody titers in patients with simple adenoma, advanced adenomatous polyp (AAP), CRC, and healthy controls, and evaluated JCV DNA in the tissue.
Ninety-seven patients undergoing colonoscopy offered to participate in the study. Normal colonoscopy, simple adenoma, AAP, and CRC were found in 41, 19, 12, and 25 cases, respectively. A blood sample was taken for JCV DNA isolation and serology. In 18 patients with CRC or AAP tissue samples were taken for JCV DNA isolation and T-antigen (T-Ag) detection.
A positive correlation was found between a JCV antibody titer and advanced colonic pathology. The average titer for normal controls, simple polyp, AAP, and CRC was 2.61+/-0.72, 2.95+/-0.77, 3.33+/-0.76, and 3.30+/-0.50 log, respectively (P<0.001). Viral DNA could not be shown in the serum. The presence of neoplastic tissue T-Ag (in 33.3% of the patients) was not associated with a difference in the log titer of serum antibody.
In this study we showed that patients with advanced neoplasia, compared with patients with normal colonoscopy, harbor a higher JCV antibody titer in the serum. If confirmed, our finding may serve as a marker for CRC or for an earlier stage of AAP.
Journal of clinical gastroenterology 08/2010; 44(7):489-94. · 2.21 Impact Factor