Polymorphisms of 5-HTT LPR and GNß3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.

OBJECTIVES: The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNß3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNß3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy. METHODS: Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNß3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods. RESULTS: GNß3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy-Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNß3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43). CONCLUSIONS: GNß3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.

Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

BACKGROUND & AIMS: Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. METHODS: We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. RESULTS: An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. CONCLUSIONS: Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

Atypical Autosomal-Dominant Inheritance of Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) was previously believed to be an autosomal recessive disease. We present a patient with only one pathogenic variation of the MEFV gene due to the c.2177T>C mutation. The patient had clinical features of recurrent fevers and abdominal pain, serositis, and a history of multiple abdominal surgeries for pain. He was eventually diagnosed with FMF. This case report demonstrates an example of the rare autosomal-dominant phenotype of FMF.

Recurrent Perihepatic Abscesses Arising from a Gastric Remnant Leak: Delayed Complication of a Revision Roux-en-Y Gastric Bypass.

Roux-en-Y gastric bypass is a procedure commonly used for weight loss associated with improved outcomes and decreased complications when compared to some counterparts. The procedure involves restriction of the stomach that is achieved by creation of a gastric pouch and bypass of the duodenum and a portion of the jejunum to aid in restrictive and malabsorptive weight loss. While many complications, both early and late, have been described following the procedure, recurrent perihepatic abscess has not been described in the literature. We present a case of a 66-year-old woman with recurrent extrahepatic abscesses following revision of a Roux-en-Y gastric bypass.

Evaluation of Serum-Derived Bovine Immunoglobulin Protein Isolate in Subjects With Decompensated Cirrhosis With Ascites.

Background Bacterial translocation plays a pivotal role in the natural course of cirrhosis and its complications. Serum-derived bovine immunoglobulin (SBI) is an oral medical food that has been shown to both reduce inflammation in the intestines and neutralize bacteria. It represents a unique intervention that has not been studied in this population. Methodology We conducted a prospective open-label trial with an eight-week treatment phase of SBI. Individuals were assessed using lactulose breath testing, serum markers for enterocyte damage and bacterial translocation, and the Chronic Liver Disease Questionnaire (CLDQ) prior to and after completion of the treatment phase. Results We evaluated nine patients with a diagnosis of decompensated cirrhosis with ascites. Subjects had a mean Model for End-Stage Liver Disease (MELD) score of 11.6 ± 3.0 and were not taking lactulose or antibiotics. All subjects tolerated SBI well with no significant adverse events or changes to any of the six domains of the CLDQ. Laboratory tests including liver tests and MELD score remained stable over the course of treatment. There were no significant changes in the rates of small intestinal bacterial overgrowth (55.6% vs 55.6%, p = 1.00) or serum levels of lipopolysaccharide-binding protein, intestinal fatty acid-binding protein, or soluble CD14 (p-values 0.883, 0.765, and 0.748, respectively) when comparing values prior to and immediately after treatment. Conclusions No adverse events or significant changes to the quality of life were detected while on treatment. There were no statistically significant differences in our outcomes when comparing individuals before and after treatment in this small prospective proof-of-concept pilot study. Further prospective randomized studies could be beneficial.

Cholestatic Hepatitis as a Possible Paraneoplastic Syndrome of Endometrial Carcinoma.

Cholestatic hepatitis has not been reported as a paraneoplastic syndrome of endometrial adenocarcinoma to our knowledge. We present a patient who, shortly after endometrial adenocarcinoma diagnosis, presented with elevated liver chemistries in the setting of an acute, paraneoplastic sensorimotor polyneuropathy. Infectious, autoimmune, pharmacologic, malignant, metabolic, and structural causes of cholestatic hepatitis were screened for and ruled out. Our patient was diagnosed with simultaneous cholestatic hepatitis and acute sensorimotor polyneuropathy as possible paraneoplastic syndromes of endometrial adenocarcinoma. Clinicians should include paraneoplastic processes of cancer in the differential diagnosis for liver injury, especially when workup for alternative causes is unrevealing.

Cervical Cancer Screening in Inflammatory Bowel Disease: Who Should Be Screening?

BACKGROUND: Immunosuppressed women with inflammatory bowel disease (IBD) are at elevated risk of cervical cancer yet have lower screening rates. The objective of this study was to assess the familiarity with cervical cancer screening recommendations, and the perceived responsibility for implementing screening among three physician groups involved in the clinical care of women with IBD: primary care physicians (PCP), gastroenterologists (GI) and gynecologists (GYN). METHODS: We anonymously surveyed a sample of 117 PCP, 52 GYN and 35 GI physicians affiliated with Saint Louis University, Saint Louis, MO, USA, from April 2018 to January 2019. The physicians completed a questionnaire adressing essential aspects of cervical cancer screening such as screening age, screening frequency, human papillomavirus (HPV) vaccination, comfort level in performing Papanicolaou (Pap) smears, perception of physician responsibility in terms of which physicians should perform Pap smears. RESULTS: A total of 2.6% of PCPs, 37% of GIs and 29% of GYNs reported familiarity with cervical cancer screening recommendations. In addition, PCP and GI had no definite opinions regarding which physicians should be in charge of cervical cancer screening and performing Pap smears. However, 94% of GYNs felt that they should be in charge of cervical cancer screening and performing Pap smears. CONCLUSIONS: An apparent lack of familiarity exists among all three physician groups regarding cervical cancer screening recommendations in immunosuppressed patients with IBD. Similarly, there is no consensus regarding which specialty should be responsible for cervical cancer screening in this patient population.

Choices in colorectal cancer screening: a review of current screening modalities and recommendations.

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In 2008, screening recommendations for CRC were updated. Successful reduction in CRC prevalence and deaths depends on a thorough understanding and correct implementation of these guidelines. This paper reviews the most recent CRC screening guidelines, in order to promote increased screening and effective adherence to these guidelines.

Barrett's esophagus: a pre-cancerous condition approach to diagnosis and management.

Barrett's esophagus (BE) results from prolonged uncontrolled gastroesophageal reflux (GERD). Patients at risk for BE should be screened with upper endoscopy. Dysplasia is identified pathologically on endoscopic biopsy. The finding of low grade dysplasia indicates the need for more surveillance. High grade dysplasia warrants intervention with ablative techniques or surgery due to the extremely high rate of malignant transformation to esophageal adenocarcinoma. All patients should receive measures to control GERD (life-style modifications and acid suppression).

Diarrhea Concealing a Duodenal-Cecal Fistula Secondary to Appendiceal Mucinous Neoplasm.

Primary mucinous adenocarcinoma of the appendix is a rare gastrointestinal malignancy. Fistulous tract formation is a complication that is cited in literature. An 85-year-old man with multiple comorbidities presented with several weeks of persistent non-bloody diarrhea. Laboratory work-up was non-diagnostic. Abdominal imaging with barium contrast showed an enterocolonic fistulous tract extending from the duodenum to the cecum involving an enlarged appendiceal mass. Subsequent biopsy confirmed mucinous appendiceal neoplasm with peritoneal spread to the liver and mesentery. This is the first report describing an enterocolonic fistula formation resulting from this malignancy.

Fecal incontinence in the elderly patient.

Fecal incontinence is an underreported problem in the general population; it is especially common in elderly persons (aged >or=65 years) residing in the community or in long-term care settings. It affects more women than men during younger years, but this differential narrows with age. Physiological changes such as sphincter muscle and sensory abnormalities in the anorectal region contribute to this problem, as do factors such as dementia, physical disability, and fecal impaction. Treatment with biofeedback is feasible in many elderly patients. Those with advanced dementia or physical disability may benefit from a bowel habit training program. Selected patients may require surgical sphincter repair. Minimally invasive techniques such as radiofrequency energy application offer promising future treatment options. The purpose of this review is to provide current information on fecal incontinence and its management in the elderly.

Subtypes of constipation: sorting out the confusion.

In patients with chronic constipation, identifying subtypes based on underlying physiology guides subsequent therapeutic choices. Chronic constipation subtypes include slow-transit constipation, pelvic floor dyssynergia, functional constipation, and irritable bowel syndrome with constipation. Chronic constipation subtypes are defined by the result of colonic transit, pelvic floor function, and the presence or absence of significant abdominal pain. Although a variety of tests are available, the most straightforward approach uses the 5-day colonic marker test of transit and anorectal manometry with balloon expulsion testing to evaluate for pelvic floor dysfunction. Patients with normal physiologic tests have either irritable bowel syndrome with constipation or normal-transit constipation. Significant overlap exists between subtypes and a clear distinction is not always possible, with up to a 50% overlap between patients with slow-transit constipation and irritable bowel syndrome, approximately 10% of patients evaluated exhibiting both slow transit and pelvic floor dyssynergia, and 50% of patients with pelvic floor dyssynergia also found to have slow transit. Symptom severity assessment provides the rationale for pursuing further testing and directing the aggressiveness of treatment as patients with greater symptom severity have reduced quality of life and poor physical functioning scores. Few constipation-specific validated measures exist for measuring symptom severity in chronic constipation. In clinical practice severity may be defined as mild symptoms having minimal impact upon daily activities or moderate to severe symptoms that increasingly interfere with daily life.

Gastrointestinal causes of abdominal pain.

Gastrointestinal causes of abdominal pain are numerous. These causes are reviewed in brief here, divided into 2 categories: acute abdominal pain and chronic abdominal pain. They are further subcategorized by location of pain as it pertains to the abdomen.

Functional Dyspepsia Treatment Trial (FDTT): a double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics.

BACKGROUND: Functional dyspepsia (FD) is a common problem affecting up to 10-25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. OBJECTIVES: The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. DESIGN: The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNß3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. METHODS: The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651).

Multimodality diagnostic imaging of diffuse esophageal leiomyomatosis.

A case of diffuse esophageal leiomyomatosis is presented, with emphasis on the imaging findings across multiple contemporary diagnostic modalities. This entity represents a rare presentation of uncommon benign smooth muscle tumors of the esophagus. The characteristic clinical, histologic, and multimodality imaging findings may distinguish this benign tumor from its malignant counterpart leiomyosarcoma and from achalasia.

Measurement of gastrointestinal transit.

An abnormality in transit is commonly considered to account for unexplained gastrointestinal (GI) symptoms. Since the symptoms of delayed transit overlap with those of accelerated transit, direct measurement of GI transit is needed to establish an accurate diagnosis. Similarly, since symptoms originating from one part of the gut may overlap with symptoms from another, localizing transit abnormality to one organ vs. another using direct measurement is an important part of diagnostic evaluations. Consequently, noninvasive tests of GI transit should be done early in the evaluation to guide therapy. We now have tools to measure transit accurately; results of transit tests often depend on the conditions selected for the test, so test results will match clinical expectations most closely when test conditions are selected to reproduce the circumstances for symptom production. This review describes the most commonly used methods for the measurement of GI transit including the gastric emptying test for some dyspeptic symptoms, small bowel transit test for dyspeptic symptoms and diarrhea, colonic transit test for constipation, and factors that influence the result of these studies. As we make progress in our understanding of the pathophysiology of transit disorders, the clinical usefulness of these diagnostic tests will be further enhanced.