Safety of Endoscopy in Heritable Connective Tissue Disorders.

INTRODUCTION: Little is known about the gastrointestinal manifestations or safety of endoscopy among patients with heritable connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome (EDS). METHODS: We conducted an electronic cross-sectional survey nested within preexisting registries of patients with heritable connective tissue disorders and examined self-reported rates of endoscopic complications. RESULTS: The rate of endoscopy-related perforation was 9.4% (95% confidence interval 2.0%-25.0%) among individuals with vascular EDS, <1% in classical and hypermobility-type EDS, and zero in Marfan syndrome (P < 0.001). Spontaneous intestinal perforation was also significantly higher in the vascular EDS group. DISCUSSION: Clinicians should consider noninvasive screening methods for patients with vascular EDS.

Sclerosing Mesenteritis.

Sclerosing mesenteritis is a rare non-neoplastic disorder characterized by fat necrosis, chronic inflammation, and fibrosis typically of the small bowel mesentery. Our understanding of this disorder is limited by its rarity as well as inconsistent terminology used across the literature. While prior abdominal surgery or trauma, autoimmunity, infection, ischemia, and malignancy have been suggested to be involved in the pathogenesis of the disorder, it remains poorly understood. The clinical course of sclerosing mesenteritis is generally benign with a large proportion of patients diagnosed incidentally on imaging obtained for other indications. In a subset of patients, symptoms may arise from a mass effect on the bowel, lymphatics, or vasculature resulting in bowel obstruction, chylous ascites, or mesenteric ischemia. Symptomatic patients should be treated with a combination of corticosteroid and tamoxifen as first-line therapy based on retrospective case series and experience in other fibrosing disorders. Surgical intervention may be required in those with persistent obstruction despite conservative treatment, though complete resection of the mass is often not feasible given intimate involvement with the mesenteric vasculature. A careful use of terminology and communication between the radiologist, pathologist, and clinicians in the care of these patients will be essential to future efforts at understanding this disease.

Encapsulating peritoneal sclerosis.

Encapsulating peritoneal sclerosis (EPS) is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions. EPS is most commonly associated with long-term peritoneal dialysis, though medications, peritoneal infection, and systemic inflammatory disorders have been implicated. Many cases remain idiopathic. Diagnosis is often delayed given the rarity of the disorder combined with non-specific symptoms and laboratory findings. Although cross-sectional imaging with computed tomography of the abdomen can be suggestive of the disorder, many patients undergo exploratory laparotomy for diagnosis. Mortality approaches 50% one year after diagnosis. Treatment for EPS involves treating the underlying condition or eliminating possible inciting agents (i.e. peritoneal dialysis, medications, infections) and nutritional support, frequently with total parenteral nutrition. EPS-specific treatment depends on the disease stage. In the inflammatory stage, corticosteroids are the treatment of choice, while in the fibrotic stage, tamoxifen may be beneficial. In practice, distinguishing between stages may be difficult and both may be used. Surgical intervention, consisting of peritonectomy and enterolysis, is time-consuming and high-risk and is reserved for situations in which conservative medical therapy fails in institutions with surgical expertise in this area. Herein we review the available literature of the etiology, pathogenesis, diagnosis, and treatment of this rare, but potentially devastating disease.

Acute Fatty Liver Disease of Pregnancy: Updates in Pathogenesis, Diagnosis, and Management.

Acute fatty liver of pregnancy (AFLP) is an obstetric emergency characterized by maternal liver failure and may have complications for the mother and fetus, including death. This review examines recent literature on the epidemiology, pathogenesis, diagnosis, and treatment of acute fatty liver of pregnancy. Pathogenesis of this disease has been linked to defects in fatty acid metabolism during pregnancy, especially in the setting of fetal genetic defects in fatty acid oxidation. The value of screening all patients for these genetic defects remains to be determined. Distinguishing AFLP from other high-risk liver diseases of pregnancy that have overlap features, such as HELLP and preeclampsia, can be challenging. Although sensitive diagnostic tools such as the Swansea criteria have been developed, further work is needed to diagnose AFLP more quickly. Although survival rates have improved in the past 30 years, delay in diagnosis and treatment of AFLP has life-threatening consequences; an algorithmic approach to AFLP may be a valuable resource for clinicians. Future epidemiological and long-term studies will improve our prediction of women at risk for developing AFLP and determine the long-term consequences of this condition.

Histology Grade Is Independently Associated With Relapse Risk in Patients With Ulcerative Colitis in Clinical Remission: A Prospective Study.

OBJECTIVES: Objective evidence of inflammation has been associated with the risk of relapse in patients with ulcerative colitis (UC) who are in clinical remission. We compared endoscopic and histologic grades for their ability to predict clinical relapse in this patient population. METHODS: Patients with UC in clinical remission were prospectively enrolled into an observational cohort. Baseline endoscopic scores (Mayo) and histological (Geboes) grades and blood markers were collected. All subjects were followed for 12 months and relapse determined using clinical indices. RESULTS: A total of 179 subjects were enrolled into the study and followed for 12 months. Clinical relapse occurred in 23%; 5% were hospitalized, and 2% underwent colectomy. In univariate analysis, the baseline Mayo endoscopy score and the Geboes histology grade were significantly associated with the later development of clinical relapse (P<0.001 for both), but only the histology grade remained significant in a multivariate model (P=0.006). The relative risk of clinical relapse was 3.5 (95% CI 1.9-6.4, P<0.0001) in subjects whose baseline Geboes grade was ≥3.1. The area under the curve was 0.73 for the Geboes histology grade to identify subjects at risk of future clinical relapse. Of the patients in clinical, endoscopic, and histological remission at baseline (n=82), only 7% had a clinical relapse over the subsequent 12 months. CONCLUSIONS: Histology grade has the strongest association with the risk of clinical relapse in patients with UC who are in clinical remission. Consideration should be given to including this end point in evaluating therapy for UC.

Complementary and Alternative Medicine Use Is Prevalent Among Patients with Gastrointestinal Diseases.

INTRODUCTION: Complementary and alternative medicine (CAM) use is reported to be higher among patients with irritable bowel syndrome and inflammatory bowel disease; however, demographic predictors and reasons for utilization for all GI conditions are less clear. AIM: To determine prevalence, predictors, and reasons for CAM use among all patients attending a gastrointestinal (GI) clinic in a single academic center. METHODS: Adults attending outpatient GI clinics at Beth Israel Deaconess Medical Center completed a questionnaire to assess CAM utilization as well as perceived benefits, harms, and costs of CAM therapy. Fisher's exact test was used to compare statistical differences between CAM and non-CAM users. RESULTS: Survey questionnaires were completed by 269 patients. Prevalence of CAM use was 44 % (95 % CI 38-50). Users were more likely to be female (81 vs. 56 %, p < 0.01) and dissatisfied with conventional treatment (22 vs. 8 %, p < 0.01). There was no significant difference in age, race, education, income, GI diagnosis, and duration of symptoms between the two groups. Users reported "wish to feel generally better" as main reason for utilization, and a majority of patients (62 %) experienced improved GI symptoms. Among patients who did not discuss CAM with their physicians (30 %), they cited physician failure to ask about CAM as the major reason (82 %). CONCLUSION: CAM is prevalent among patients attending a GI clinic, particularly among women and those who are dissatisfied with conventional therapies and "wish to feel better." Greater awareness and understanding of CAM among GI physicians is necessary.

Complementary and alternative medicine and mind-body therapies for treatment of irritable bowel syndrome in women.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, characterized by chronic or recurrent abdominal pain with constipation, diarrhea and/or an alternation of the two, and often bloating. Complementary and alternative medicine (CAM) consists of a group of medical treatments that are not commonly considered to be a part of traditional medicine. CAM is commonly used for difficult-to-treat chronic medical conditions. Many patients choose CAM because there are only a limited number of treatments available for IBS or because they would like to have a 'natural therapy'. Mind-body therapies for IBS have proven efficacy, but have not been well accepted by patients or practitioners for treatment. This article reviews the use of CAM and mind-body therapies in IBS, with a focus on probiotics, acupuncture, herbal medicines and psychological therapies.

Histologic markers of inflammation in patients with ulcerative colitis in clinical remission.

BACKGROUND & AIMS: Mucosal healing, based on histologic analysis, is an end point of maintenance therapy for patients with ulcerative colitis (UC). There are few data on how histologic signs of inflammation correlate with endoscopic and peripheral blood measures of inflammation in these patients. We investigated patterns of histologic features of inflammation in patients with UC in clinical remission, and correlated these with endoscopic and biochemical measures of inflammation. METHODS: We performed a prospective observational study of 103 patients with UC in clinical remission undergoing surveillance colonoscopy while receiving maintenance therapy with mesalamine or thiopurines; 2674 biopsy specimens were collected from 708 colonic segments. Each colonic segment was evaluated based on the Mayo endoscopic subscore and the Geboes histology score (range, 0-5.4). Biomarkers were measured in peripheral blood samples. RESULTS: Histologic features of inflammation were found in 54% of patients receiving maintenance therapy; 37% had at least moderate inflammation based on histology scores. Of the 52 patients with endoscopic evidence only of left-sided colitis, 34% had histologic features of inflammation in their proximal colon. Histology scores correlated with endoscopic scores for per-segment inflammation (Spearman ρ = 0.65; P < .001). Patients with histology scores greater than 3.1 had a significantly higher mean level of C-reactive protein than those with scores less than 3.1. There were no differences among treatment groups in percentages of patients with histologic scores greater than 3.1. CONCLUSIONS: Patients in clinical remission from UC still frequently have histologic features of inflammation, which correlate with endoscopic appearance. Patients with at least moderate levels of inflammation, based on histologic grading (score >3.1), have higher serum levels of C-reactive protein, which could be used as a surrogate marker of histologic inflammation.

Predictors of endoscopic inflammation in patients with ulcerative colitis in clinical remission.

BACKGROUND: Patients with ulcerative colitis (UC) who are in clinical remission may still have underlying endoscopic inflammation, which is associated with inferior clinical outcomes. The goal of this study was to determine the prevalence of active endoscopic disease, and factors associated with it, in patients with UC who are in clinical remission. METHODS: Prospective observational study in a single center. Patients with UC in clinical remission (by Simple Clinical Colitis Activity Index) were enrolled prospectively at the time of surveillance colonoscopy. Disease phenotype, endoscopic activity (Mayo subscore), and histologic score (Geboes) were recorded, and blood was drawn for peripheral blood biomarkers. RESULTS: Overall, 149 patients in clinical remission were prospectively enrolled in this cohort; 81% had been in clinical remission for >6 months, and 86% were currently prescribed maintenance medications. At endoscopy, 45% of patients in clinical remission had any endoscopic inflammation (Mayo endoscopy subscore >0), and 13% had scores >1. In a multivariate model, variables independently associated with a Mayo endoscopic score >1 were remission for <6 months (P = 0.001), white blood count (P = 0.01), and C-reactive protein level (P = 0.009). A model combining these 3 variables had a sensitivity of 94% and a specificity of 73% for predicting moderate-to-severe endoscopic activity in patients in clinical remission (area under the curve, 0.86). In an unselected subgroup of patients who had peripheral blood mononuclear cell messenger RNA profiling, GATA3 messenger RNA levels were significantly higher in patients with endoscopic activity. CONCLUSIONS: Duration of clinical remission, white blood count, and C-reactive protein level can predict the probability of ongoing endoscopic activity, despite clinical remission in patients with UC. These parameters could be used to identify patients who require intensification of treatment to achieve mucosal healing.

Colorectal cancer screening and prevention in women.

Colorectal cancer (CRC) is the third most common cause of cancer in women. Screening for CRC increases early detection of cancer and premalignant polyps and decreases morbidity from this disease. However, adherence to the screening guidelines continues to remain inadequate both at the physician and patient levels. Several factors are of special importance to women. Presence of prior gynecological malignancies may increase the risk of CRC in women. Furthermore, new studies have shown other factors such as obesity and smoking to increase the risk of CRC in women. This article highlights issues unique to women with regards to CRC and outlines special considerations for determining screening intervals in women, identifies factors that make screening more difficult in women, and reviews studies that identify preventative strategies which, together with screening, may reduce the burden of CRC.

Uniquely women's issues in colorectal cancer screening.

Colorectal cancer (CRC) is the third most common cause of cancer in women. Screening has been shown to increase detection and decrease morbidity from this disease, but compliance is poor. This paper reviews special considerations for determining screening intervals in women, factors making screening more difficult in women, and studies reviewing preventative strategies in addition to screening that may reduce CRC.

Therapy insight: drugs for gastrointestinal disorders in pregnant women.

The management and treatment of gastrointestinal ailments in pregnant women requires special attention and expertise, since the safety of the mother, fetus and neonate remains the primary focus. Nausea and vomiting during pregnancy is common, as is symptomatic gastroesophageal reflux disease. Peptic ulcer disease occurs less frequently and with fewer complications. Gastroenterologists and obstetricians should be familiar with safe treatment options for these conditions, because they can profoundly impair the quality of life of pregnant women. During pregnancy, constipation can develop de novo, or chronic constipation can increase in severity. Given the array of therapies for constipation, physicians must apprise themselves of drugs that are safe for both mother and fetus. Management of acute, self-limited diarrhea should focus on supportive therapy, dietary changes and maintenance of hydration. Treatment of chronic diarrhea should be considered in the context of therapy for the underlying disorder. Inflammatory bowel disease and irritable bowel syndrome present a unique therapeutic challenge--to control the disease while minimizing toxicity to the fetus and mother. Initiation and alteration of medical therapy for gastrointestinal disorders during pregnancy must be undertaken after discussion with the patient's obstetrician.