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Amanda M Pattison, Dante J Merlino, Erik S Blomain, Scott A Waldman
Colorectal cancer (CRC) is a major cause of cancer-related mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C (GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells, plays an important role in orchestrating intestinal homeostatic mechanisms...
September 28, 2016: World Journal of Gastroenterology: WJG
John Rafferty, Hema Nagaraj, Alice P McCloskey, Rawan Huwaitat, Simon Porter, Alyaa Albadr, Garry Laverty
Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or monotherapy for prostate and breast cancer, and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T...
September 9, 2016: Current Medicinal Chemistry
Irene Sonu, George Triadafilopoulos, Jerry D Gardner
BACKGROUND: Clinical trials of several new treatments for opioid-induced constipation (OIC), chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) have focused on differences between subjects relieved of constipation with placebo and active treatment. Patients and clinicians however, are more interested in the probability these treatments provide actual relief of constipation and its associated symptoms. METHODS: We searched the medical literature using MEDLINE and Cochrane central register of controlled trials...
2016: BMJ Open Gastroenterology
Jan Tack, Tim Vanuytsel, Maura Corsetti
In the treatment of irritable bowel syndrome (IBS), loperamide seems efficacious for diarrhea and ispaghula for constipation, while musculotropic spasmolytics may relieve abdominal pain. Antidepressants were found to be efficacious for abdominal pain, but their tolerance may be problematic and the therapeutic effect varied largely between trials. While meta-analyses suggest efficacy of probiotics as a group, the quality of the trials is often suboptimal and there is large variability. Lubiprostone, a chloride channel activator, and linaclotide, a guanylyl cyclase-C agonist, showed favorable effects on multiple symptoms in IBS with constipation...
2016: Digestive Diseases
Fermín Mearin, Constanza Ciriza, Miguel Mínguez, Enrique Rey, Juan José Mascort, Enrique Peña, Pedro Cañones, Javier Júdez
In this Clinical Practice Guideline we discuss the diagnostic and therapeutic approach of adult patients with constipation and abdominal complaints at the confluence of the irritable bowel syndrome spectrum and functional constipation. Both conditions are included among the functional bowel disorders, and have a significant personal, healthcare, and social impact, affecting the quality of life of the patients who suffer from them. The first one is the irritable bowel syndrome subtype, where constipation represents the predominant complaint, in association with recurrent abdominal pain, bloating, and abdominal distension...
June 2016: Revista Española de Enfermedades Digestivas
Enrique Rey Díaz-Rubio, Juan José Mascort Roca, Enrique Peña Forcada, Pedro Cañones Garzón, Jose María Tenias Burillo, Francisco Javier Júdez Gutiérrez
Irritable bowel syndrome and functional constipation represent a relevant and common health issue. However, real-world clinical practice includes patients with constipation who may or may not have other abdominal complaints (pain, bloating, abdominal discomfort) with variable frequency. The goal of the present study was to obtain information on the workload entailed by patients with constipation and associated abdominal complaints, predominant clinical behaviors, education needs, and potential daily practice aids both in Primary Care and gastroenterology settings...
June 2016: Revista Española de Enfermedades Digestivas
Manhal Izzy, Anju Malieckal, Erin Little, Sury Anand
AIM: To study the efficacy and safety of pharmacological treatment of constipation in geriatrics. METHODS: PubMed, MEDLINE, google scholar, and Ovid were searched to identify human studies performed on the use of laxatives in elderly with constipation, which were conducted between January 1990 and January 2013 using the specified keywords. Controlled studies that enrolled geriatric patients with a diagnosis of constipation and addressed the efficacy and/or the safety of pharmacological treatments were included...
May 6, 2016: World Journal of Gastrointestinal Pharmacology and Therapeutics
Amy E Foxx-Orenstein
Irritable bowel syndrome is a functional bowel disorder with gastrointestinal symptoms (e.g. abdominal pain, straining, urgency, incomplete evacuation, nausea, and bloating) that occur alongside bowel function alterations (i.e. constipation, diarrhea, or both). Patients with irritable bowel syndrome may also experience comorbid anxiety and depression. Irritable bowel syndrome is common, with a prevalence estimated between 3% and 28%, affecting patient health and quality of life. Patients with moderate or severe irritable bowel syndrome generally seek medical care, whereas those with milder symptoms may choose self-management...
May 2016: Therapeutic Advances in Gastroenterology
Erik S Blomain, Amanda M Pattison, Scott A Waldman
Despite advances in screening and prevention strategies, colorectal cancer (CRC) remains the second-leading cause of cancer-related death in the United States. Given this continued public health burden of CRC, there is a clear need for improved disease prevention. CRC initiates and progresses over decades, canonically proceeding via a series of stepwise molecular events that turn a normal epithelium into a dysfunctional epithelium, then subsequently into an adenoma, and finally an invasive adenocarcinoma. An emerging paradigm suggests that guanylyl cyclase C (GUCY2C) functions as a tumor suppressor in the intestine, and that the loss of hormone ligands for this receptor causes epithelial dysfunction and represents an important step in the disease process...
July 2, 2016: Cancer Biology & Therapy
Satish S C Rao, Kulthep Rattanakovit, Tanisa Patcharatrakul
Constipation is a heterogeneous, polysymptomatic, multifactorial disease. Acute or transient constipation can be due to changes in diet, travel or stress, and secondary constipation can result from drug treatment, neurological or metabolic conditions or, rarely, colon cancer. A diagnosis of primary chronic constipation is made after exclusion of secondary causes of constipation and encompasses several overlapping subtypes. Slow-transit constipation is characterized by prolonged colonic transit in the absence of pelvic floor dysfunction...
May 2016: Nature Reviews. Gastroenterology & Hepatology
Huan Huang, Douglas C Aa Taylor, Robyn T Carson, Phil Sarocco, Mark Friedman, Michael Munsell, Steven I Blum, Joseph Menzin
PURPOSE: To evaluate the effectiveness and costs of linaclotide (Linzess) versus lubiprostone (Amitiza) in the treatment of adult patients with chronic idiopathic constipation (CIC). DESIGN: A decision-tree model using model inputs derived from published literature, linaclotide phase 3 trial data, and a physician survey. METHODOLOGY: Measures of treatment efficacy were selected based on comparability between trial data, with posthoc analyses of linaclotide required to ensure comparability with available lubiprostone data...
February 2016: Managed Care
Maura Corsetti, Peter Whorwell
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder, which represents a major cost to healthcare services. Current pharmacological treatment includes fibre supplements, antispasmodics, laxatives, loperamide and antidepressants. This article reviews the novel pharmacological treatments already or recently approved for patients with IBS-C (lubiprostone, linaclotide) and IBS-D (alosetron, ramosetron, rifaximin, eluxadoline). Furthermore, results for drugs in development (plecanatide, ibudutant and ebastine) or used in chronic constipation or for other indications, with potential application in IBS (prucalopride, elobixibat, mesalazine, ondansetron and colesevelam) are also reviewed...
July 2016: Expert Review of Gastroenterology & Hepatology
Jieru E Lin, Francheska Colon-Gonzalez, Erik Blomain, Gilbert W Kim, Amanda Aing, Brian Stoecker, Justin Rock, Adam E Snook, Tingting Zhan, Terry M Hyslop, Michal Tomczak, Richard S Blumberg, Scott A Waldman
Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis...
January 15, 2016: Cancer Research
Salman Nusrat, Philip B Miner
INTRODUCTION: Constipation predominant irritable bowel syndrome (IBS-C) is a common disorder and accounts for a large number of ambulatory visits. Sensory abnormalities, that is, presence of abdominal pain and discomfort, distinguish IBS-C from chronic idiopathic constipation. AREA COVERED: This review focuses on the pharmacology, efficacy, safety, and future of prucalopride, YKP-10811, DSP-6952, dexloxiglumide, linaclotide, plecanatide, tenapanor, and elobixibat...
2015: Expert Opinion on Emerging Drugs
J Pfeifer
Patients with intractable chronic constipation should be evaluated with physiological tests after structural disorders and extracolonic causes have been excluded. Conservative treatment options should be tried unstintingly. It should be pointed out that especially new drugs such as prucalopride and linaclotide seem to be a big step forward in treating patients with chronic constipation. If surgery is indicated, for many years subtotal colectomy with IRA was the treatment of choice, although segmental resections were also a good option for isolated megasigmoid, sigmoidocele or recurrent sigmoid volvulus...
September 2015: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
Brian E Lacy, William D Chey, Anthony J Lembo
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with abdominal pain, diarrhea, constipation, or a mix of symptoms. The pathophysiology of IBS is not completely understood but appears to involve genetics, the gut microbiome, immune activation, altered intestinal permeability, and brain-gut interactions. There is no gold standard for diagnosis. Several sets of symptom-based guidelines exist. Treatment strategies for IBS may include both nonpharmacologic and pharmacologic approaches...
April 2015: Gastroenterology & Hepatology
Mellar Davis, Pamela Gamier
Constipation is common in the general population and for those on opioids and/or who are suffering from advanced cancer. Self-management consists of dietary changes, exercise, and laxatives. However, responses to self-management efforts are often inadequate to relieve the subjective and objective experience of constipation. Multiple new anti-constipating medications have recently been tested in randomized trials and the following are available commercially: probiotics, prucalopride, lubiprostone, linaclotide, elobixibat, antidepressants, methylnaltrexone, alvimopan, and naloxegol...
December 2015: Current Oncology Reports
Anne Mounsey, Meghan Raleigh, Anthony Wilson
Chronic constipation is common in adults older than 60 years, and symptoms occur in up to 50% of nursing home residents. Primary constipation is also referred to as functional constipation. Secondary constipation is associated with chronic disease processes, medication use, and psychosocial issues. Fecal impaction should be treated with mineral oil or warm water enemas. Most patients are initially treated with lifestyle modifications, such as scheduled toileting after meals, increased fluid intake, and increased dietary fiber intake...
September 15, 2015: American Family Physician
Michelle Lau, Alexander C Ford
INTRODUCTION: Although there are defined criteria for the diagnosis of constipation, in practice, diagnostic criteria are less rigid and depend in part on the perception of normal bowel habit. Constipation is highly prevalent, with approximately 12 million general practitioner prescriptions for laxatives in England in 2001. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of medications in people with idiopathic chronic constipation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review)...
2015: Clinical Evidence
Brian E Lacy, Ron Schey, Steven J Shiff, Bernard J Lavins, Susan M Fox, Xinwei D Jia, Rick E Blakesley, Xinming Hao, Jacquelyn A Cronin, Mark G Currie, Caroline B Kurtz, Jeffrey M Johnston, Anthony J Lembo
BACKGROUND: Abdominal bloating is a common and bothersome symptom of chronic idiopathic constipation. The objective of this trial was to evaluate the efficacy and safety of linaclotide in patients with chronic idiopathic constipation and concomitant moderate-to-severe abdominal bloating. METHODS: This Phase 3b, randomized, double-blind, placebo-controlled clinical trial randomized patients to oral linaclotide (145 or 290 μg) or placebo once daily for 12 weeks. Eligible patients met Rome II criteria for chronic constipation upon entry with an average abdominal bloating score ≥5 (self-assessment: 0 10-point numerical rating scale) during the 14-day baseline period...
2015: PloS One
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