Systematic review and meta-analysis of lactose digestion, its impact on intolerance and nutritional effects of dairy food restriction in inflammatory bowel diseases.

BACKGROUND: Relationships between inflammatory bowel disease and lactose containing foods remain controversial and poorly defined regarding symptoms, nutritional outcomes, and epidemiologic associations for lactose maldigestion. METHODS: A literature review was performed using Pub Med, Cochrane library and individual references, to extract data on lactose maldigestion prevalence in inflammatory bowel diseases. A meta-analysis was done using selected articles, to determine odds ratios of maldigestion. Information was collected about symptoms, impact on pattern of dairy food consumption, as well as the effects of dairy foods on the course of inflammatory bowel diseases. RESULTS: A total of 1022 articles were evaluated, 35 articles were retained and 5 studies were added from review articles. Of these 17 were included in meta-analysis which showed overall increased lactose maldigestion in both diseases. However increased risk on sub analysis was only found in Crohn's in patients with small bowel involvement. Nine additional studies were reviewed for symptoms, with variable outcomes due to confounding between lactose intolerance and lactose maldigestion. Fourteen studies were evaluated for dairy food effects. There was a suggestion that dairy foods may protect against inflammatory bowel disease. Nutritional consequences of dairy restrictions might impact adversely on bone and colonic complications. CONCLUSIONS: Lactose maldigestion in inflammatory bowel disease is dependent on ethnic makeup of the population and usually not disease. No bias of increased disease prevalence was noted between lactase genotypes. Intolerance symptoms depend on several parameters besides lactose maldigestion. Dairy foods may decrease risks of inflammatory bowel disease. Dairy restrictions may adversely affect disease outcome.

Psychosocial Impact of Lynch Syndrome on Affected Individuals and Families.

INTRODUCTION: Lynch syndrome is the most common hereditary colorectal cancer syndrome, conferring a heightened risk not only of colon cancer but also of various extracolonic tumors. Studies in hereditary breast cancer have shown a negative psychological impact for patients testing positive for BRCA1 or BRCA2 mutations, but there is a paucity of literature looking at psychosocial impact of LS testing for probands and families. METHODS: A literature search of PubMed English-language articles was performed using the keywords "Lynch syndrome" combined with "psychological impact," "depression," and "anxiety." RESULTS: Lynch syndrome mutation carriers, whether or not they have had cancer, suffer a transient increase in depression and anxiety scores post-disclosure, which seem to normalize by 6-12 months. Younger patients with higher colorectal cancer risk perception, higher education level, married, and employed are more likely to accept genetic testing. Major motivators for testing are predicting one's own risk of cancer and risk to offspring. Carrier status influences family planning, and there is growing interest for preimplantation genetic diagnosis. CONCLUSIONS: Psychosocial ramifications of LS mutation positivity need to be explored further.

Rituximab-induced autoimmune hepatitis: A case study and literature review.

Rituximab is a monoclonal antibody to CD20, often used to treat B-cell lymphomas and various autoimmune diseases. While there is extensive literature on rituximab-induced liver injury related to hepatitis B reactivation, there have been no reports to date of autoimmune-type idiopathic drug-induced liver injury from this drug. We present a case of necro-inflammatory hepatitis with autoimmune features in a 40-year-old female after receiving a second dose of rituximab for mucosa-associated lymphoid tissue (MALT) lymphoma, with a review of the literature.

Endoscopist-Directed Propofol as an Adjunct to Standard Sedation: A Canadian Experience.

BACKGROUND: Sedation practices vary widely by region. In Canada, endoscopist-directed administration of a combination of fentanyl and midazolam is standard practice. A minority of cases are performed with propofol. AIMS: To describe the safety of nonanaesthetist administered low-dose propofol as an adjunct to standard sedation. METHODS: This was a single-centre retrospective study of patients having undergone endoscopic procedures with propofol sedation between 2004 and 2012 in a teaching hospital in Montreal. Procedures were performed by gastroenterologists trained in Advanced Cardiovascular Life Support. Sedation was administered by intravenous bolus by a registered nurse, under the direction of the endoscopist. Outcomes of procedures were collected in the context of a retrospective chart review using the hospital's endoscopy database. RESULTS: Of patients undergoing endoscopies at our centre, 4930 patients received propofol as an adjunct to standard sedation with fentanyl and midazolam. Cecal intubation rate for colonoscopies (n = 2921) was 92.0%. Gastroscopies (n = 1614), flexible sigmoidoscopies (n = 28), endoscopic retrograde cholangiopancreatography (n = 331) and percutaneous endoscopic gastrostomy insertion (n = 36) had success rates, defined as successful completion of the procedure within anatomical limits, of 99.0, 96.4, 94.0 and 91.7%, respectively. The average dose of propofol used for each procedure was 34.5 ± 20.8 mg. Fentanyl was used in 67.4% of procedures at an average dose of 94.3 ± 17.5 mcg. Midazolam was used in 92.7% of cases at an average dose of 3.0 ± 0.7 mg. Reversal agents (naloxone or flumazenil) were used in 0.43% of the cases (n = 21). Patients who received propofol were discharged uneventfully within the usual postprocedure recovery time. One patient required sedation-related hospitalization. For patients having received propofol in addition to standard sedation agents, 99.6% experienced no adverse events. There were no mortalities. CONCLUSION: The use of low-dose propofol as an adjunct to fentanyl and midazolam, administered by a registered nurse under the direction of the endoscopist was safe and effective in patients at our centre.

High frequency of exon deletions and putative founder effects in French Canadian Lynch syndrome families.

Lynch syndrome is one of the most common autosomal dominantly inherited cancer syndromes. Mutations in MLH1, MSH2, MSH6, and PMS2 account for greater than 98% of reported mutations in Lynch syndrome families. It has been reported that large genomic deletions in MLH1 and MSH2 are a frequent cause of Lynch syndrome in certain populations. Using a multimodal approach, we have identified mutations in MLH1, MSH2, and MSH6 in French Canadian families fulfilling the Amsterdam criteria for Lynch syndrome and who displayed abnormal staining for at least one of the Lynch syndrome proteins. Mutations were identified in 28 of our 29 French Canadian probands (97%). A total of 18 distinct mutations (nine in MLH1, seven in MSH2, two in MSH6) were identified, of which six (33%) were genomic exon deletions. Another four (22%) resulted in exon deletions in cDNA alone. Three (17%) are novel mutations. Five of these 18 mutations were detected in more than one distinct family (four in MLH1, one in MSH2) and haplotype analysis suggests the possibility of founder effects. Fifteen of the 29 (52%) families carried one of these five putative founder mutations. These findings may simplify genetic testing for Lynch syndrome in French Canadians.

Autistic enterocolitis: fact or fiction?

Autism spectrum disorder refers to syndromes of varying severity, typified by impaired social interactions, communicative delays and restricted, repetitive behaviours and interests. The prevalence of autism spectrum disorders has been on the rise, while the etiology remains unclear and most likely multifactorial. There have been several reports of a link between autism and chronic gastrointestinal symptoms. Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia and focally enhanced gastritis compared with controls. Postulated mechanisms include aberrant immune responses to some dietary proteins, abnormal intestinal permeability and unfavourable gut microflora. Two autism spectrum disorder patients with chronic intestinal symptoms and abnormal endoscopic findings are described, followed by a review of this controversial topic.

Low yield of gastroscopy in patients with Lynch syndrome.

BACKGROUND/AIMS: Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome, caused by germline mutations in mismatch-repair genes. Besides a lifetime risk of colorectal cancer averaging 70%-80%, there is an increased risk of extracolonic tumors including gastric cancer. The utility of screening gastroscopy in Lynch syndrome has long been debated. This study aimed to determine the proportion of abnormal gastroscopies among patients screened, including the incidence of gastric cancer and prevalence of precursor lesions. MATERIALS AND METHODS: Charts of patients with mutation-proven Lynch syndrome between January 1, 2004, and December 31, 2014, from the Genetics clinic and Hereditary Gastrointestinal Cancer Clinic of our institution were retrospectively reviewed. RESULTS: A total of 66 Lynch syndrome patients were identified. Thirty-two gastroscopies were performed in 21 (32%) of them. No gastric cancers were found. The prevalence of precursor lesions (Helicobacter pylori gastritis, atrophic gastritis, and gastric intestinal metaplasia) was 19.05%. A family history of gastric cancer was associated with a non-significant increased risk of abnormal gastroscopy, while sex and specific gene involved did not affect the abnormality rate. CONCLUSION: Gastric screening in asymptomatic individuals with Lynch syndrome is probably best reserved for high-risk individuals, based on the family history and perhaps ethnicity as suggested by several governing bodies. Larger studies are required to achieve the statistical power necessary to address this controversial issue.

Colonic manifestation of a haematologic disorder.

A 32year-old female presenting with right lower quadrant pain was found to have caecal varices. Extensive work-up revealed underlying protein C deficiency.

Accuracy of biopsies for Helicobacter pylori in the presence of intestinal metaplasia of the stomach.

BACKGROUND/AIMS: Gastric cancer is the second leading cause of cancer-related death worldwide. The majority of gastric cancers is "intestinal-type" adenocarcinoma, caused in part by H. pylori infection. Chronic gastritis leading to atrophy and intestinal metaplasia (IM) can result in cancer. Studies have demonstrated reversibility of mucosal atrophy following H. pylori eradication. Concern has been raised regarding the sensitivity of gastric biopsy for H. pylori detection in the context of IM. MATERIALS AND METHODS: All cases of IM on gastric biopsy from a single gastroenterologist's outpatient practice were retrospectively reviewed from February 1, 2006 until May 31, 2012. RESULTS: In total, 105 IM cases were found, of which 37 (35.2%, 95% CI: 26.3-45.2) were H. pylori-positive on biopsy. Charts of the remaining 68 patients were reviewed for availability of other tests, namely urea breath test (UBT) and serology. Of 43 H. pylori-negative patients who underwent a UBT, 10 were positive for the infection (23.3%, 95% CI: 12.3-39.0). Amongst patients with coexisting autoimmune gastritis (AIG), 4 out of 9 (44.4%, 95% CI: 15.3-77.3) also had evidence of H. pylori infection by UBT, despite negative histology. CONCLUSION: For cases of gastric IM with negative histology for H. pylori, UBT should be considered, even in cases of AIG, as this may alter the management and clinical course for patients.

Cytomegalovirus complicating inflammatory bowel disease: a 10-year experience in a community-based, university-affiliated hospital.

There is an ongoing debate regarding the signifcance of cytomegalovirus (CMV) in colonic biopsies and the effect of antiviral therapy in patients with infammatory bowel disease (IBD). In order to evaluate the possible impact of CMV disease on IBD patients, we reviewed charts of patients admitted through the emergency department with diagnoses of IBD and CMV over a 10-year period (January 2000 to November 2009). Laboratory test results and pharmacology databases were scrutinized, and pathology slides were re-evaluated when possible. The control group consisted of a historical group of IBD patients with fares who had been similarly evaluated in the emergency department but who did not have a diagnosis of CMV. Both chi-square tests and the student's t-test were used for analysis. The study consisted of 31 patients with IBD and CMV (median age, 60 years; 65% male; 58% ulcerative colitis patients). Immunohistochemistry confirmed the diagnosis in 19 cases (61%). Nine patients with CMV and IBD underwent a colectomy (29%) compared to 65 of the 581 patients in the control group (11.2%), who were evaluated during the same time period but did not have CMV (P=.007). Mortality was similar in both groups. Of the patients with CMV, 11 received ganciclovir. No significant differences in outcomes were noted with antiviral therapy. Although CMV disease is relatively uncommon in IBD patients, its presence may designate an increased risk for colectomy for reasons that are not yet clear. Patient outcomes may be independently affected by age and comorbidities. Systematic prospective studies could help determine the true effects of CMV on IBD patients.

Acinic cell carcinoma of the retromolar trigone region: expanding the tumor phenotype in Cowden syndrome?

Cowden syndrome (CS) is a cancer predisposition syndrome caused by germline mutations in the PTEN tumor suppressor gene. It is associated with an increased risk of thyroid, breast and endometrial cancer but many manifestations can be found in the head and neck region, some of which are pathognomonic. Here we report a 35-year-old male referred by his dentist for evaluation of a lesion located near the retromolar trigone. Comprehensive clinical examination revealed papillomatous skin lesions, macrocephaly and gingival hypertrophy. Histopathological examination of the lesion showed an acinic cell carcinoma (ACC) of minor salivary gland origin. Analysis of the PTEN gene identified a germline R130Q mutation in exon 5, confirming the diagnosis of CS, but no loss of heterozygosity was seen in DNA extracted from tumor tissue. This is to our knowledge the first case describing an association of ACC of the minor salivary gland with a PTEN-gene related disorder. It emphasizes the importance of head and neck examination in these patients.

Familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal-dominant colorectal cancer syndrome, caused by a germline mutation in the adenomatous polyposis coli (APC) gene, on chromosome 5q21. It is characterized by hundreds of adenomatous colorectal polyps, with an almost inevitable progression to colorectal cancer at an average age of 35 to 40 yr. Associated features include upper gastrointestinal tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, and other extracolonic malignancies. Gardner syndrome is more of a historical subdivision of FAP, characterized by osteomas, dental anomalies, epidermal cysts, and soft tissue tumors. Other specified variants include Turcot syndrome (associated with central nervous system malignancies) and hereditary desmoid disease. Several genotype-phenotype correlations have been observed. Attenuated FAP is a phenotypically distinct entity, presenting with fewer than 100 adenomas. Multiple colorectal adenomas can also be caused by mutations in the human MutY homologue (MYH) gene, in an autosomal recessive condition referred to as MYH associated polyposis (MAP). Endoscopic screening of FAP probands and relatives is advocated as early as the ages of 10-12 yr, with the objective of reducing the occurrence of colorectal cancer. Colectomy remains the optimal prophylactic treatment, while the choice of procedure (subtotal vs proctocolectomy) is still controversial. Along with identifying better chemopreventive agents, optimizing screening of extracolonic cancers and applying new radiological and endoscopic technology to the diagnosis and management of extracolonic features are the major challenges for the future.

Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts.

There are only a few anecdotal reports of cytomegalovirus (CMV) colitis in immunocompetent hosts. The impact of the disease in this patient population remains poorly understood. The aim of this study was to perform a meta-analysis using individual patient data to determine outcomes of CMV colitis in immunocompetent patients and identify risk factors that might influence prognosis. A literature search was performed from 1980 to 2003 looking for immunocompetent patients with CMV colitis. Immunocompetence was defined as absence of congenital or acquired immune deficiency, transplant, or immunosuppressive medication. Patients were divided by age (<55 versus > or =55) and grouped according to coexisting illnesses. Kaplan-Meier curves were plotted to assess survival. Variables included age, sex, site of acquisition of infection, extent of disease, coexisting illnesses, and treatment modality. A total of 44 patients were identified, with an average age of 61.1. Only 10 were free of any comorbidity. The mean follow-up was 13.4 months. Spontaneous remission occurred in 31.8%, mostly individuals <55 years old. Fourteen deaths occurred, all of which were in patients >55. There was a higher mortality rate among male patients > or =55 (56.9%; P = 0.08), patients with immune-modulating diseases (75.2%; P = 0.10), and those having a colectomy (68.9%; P = 0.09). This analysis underlines the rarity of CMV colitis in patients with an intact immune system. Advanced age, male gender, presence of immune-modulating comorbidities, and need for surgical intervention are factors negatively influencing survival. Conversely, young healthy patients have a good prognosis with no intervention.