Examining linaclotide for the treatment of chronic idiopathic constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is characterized by infrequent bowel movements and hard stools lasting for at least three months or longer. This disease affects 8-12% of the US population and 10-17% of the world population. Treatment and management involve identifying the primary cause, changing dietary habits, and adequate physical activity. Linaclotide is a guanylate cyclase-agonist acting locally in the luminal surface of the intestinal enterocyte leading to a signal transduction cascade, activation of the cystic fibrosis transmembrane conductance regulator (CFTR), thus increasing secretion of chloride and bicarbonate into the intestinal lumen with eventual increased intestinal fluid and faster transit time. AREAS COVERED: We reviewed multiple studies and did a thorough literature review on CIC including its pathophysiology. Through this literature review, we were able to discuss and give the context and rationale for drug regimens indicated for CIC. EXPERT OPINION: The era we live in right now is akin to nutrient-rich and fertilized soil as knowledge and resources are abundant. The opportunities and potential are endless. Constipation being more extensively studied, our understanding of medications and diseases broadens, leading to novel medications being discovered. Linaclotide is a pioneer in this aspect and can pave the way for future generations.

Transanal proximal rectosigmoidectomy: a single-center experience in surgically treated severe medically refractory idiopathic constipation.

PURPOSE: To present the functional results after a transanal proximal rectosigmoidectomy in patients with severe idiopathic constipation in which medical treatment has failed. METHODS: Patients with severe idiopathic constipation who underwent transanal proximal rectosigmoidectomy (TPRS) at Children's Hospital Colorado between June 2019 and March 2024 were included in the study. We compared multiple pre- and post-operative outcome measures and the patient's bowel regimen before and after resection. RESULTS: Fourteen patients underwent TPRS, 10 of whom were male. The average age at the time of surgery was 10.1 years (range 5-19). Seven patients have moderate to severe autism. Constipation-related clinic visits, family calls, procedural intervention, emergency room visits, and hospitalizations notably decreased frequency after TPRS. Laxative dosages and enema volume requirements were also reduced after surgery. Before surgery, all the patients suffered from daily fecal accidents, while post-operatively, all were completely free of stool accidents. CONCLUSION: In our experience, for patients who suffer from severe medically refractory idiopathic constipation, TPRS has provided improvement in their symptoms and decreased the complications inherent to this chronic disease. Parents and patients attest to a profound positive transformation in their quality of life after surgery.

Surgery for chronic idiopathic constipation: pediatric and adult patients - a systematic review.

BACKGROUND: Chronic idiopathic constipation (CIC) is a substantial problem in pediatric and adult patients with similar symptoms and workup; however, surgical management of these populations differs. We systematically reviewed the trends and outcomes in the surgical management of CIC in pediatric and adult populations. METHODS: A literature search was performed using Ovid MEDLINE, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov between January 1, 1995 and June 26, 2020. Clinical trials and retrospective and prospective studies of patients of any age with a diagnosis of CIC with data of at least 1 outcome of interest were selected. The interventions included surgical resection for constipation or antegrade continence enema (ACE) procedures. The outcome measures included bowel movement frequency, abdominal pain, laxative use, satisfaction, complications, and reinterventions. RESULTS: Adult patients were most likely to undergo resection (94%), whereas pediatric patients were more likely to undergo ACE procedures (96%) as their primary surgery. Both ACE procedures and resections were noted to improve symptoms of CIC; however, ACE procedures were associated with higher complication and reintervention rates. CONCLUSION: Surgical management of CIC in pediatric and adult patients differs with pediatric patients receiving ACE procedures and adults undergoing resections. The evaluation of resections and long-term ACE data in pediatric patients should be performed to inform patients and physicians whether an ACE is an appropriate procedure despite high complication and reintervention rates or whether resections should be considered as an initial approach for CIC.

Efficacy and safety of vibrating capsule in treatment of chronic idiopathic constipation: a systematic review and meta-analysis of randomized controlled trials.

Background: Multiple pharmacological interventions and modalities are available for managing chronic idiopathic constipation (CIC), with variable efficacy. Vibrating capsule (VC) is a device that has shown variable results in alleviating constipation by tactile stimulation of the colonic wall and inducing peristalsis. This meta-analysis is to investigate the efficacy and safety of this modality. Methods: Comprehensive literature search was performed through June 14th, 2023, on databases including Embase, PubMed/MEDLINE, Cochrane Central, Web of Science, Global Index Medicus, and Google Scholar. Core concepts of VC, constipation, and bowel movement were searched. The DerSimonian-Laird method and random effects model were utilized. We calculated odds ratio (OR) and mean difference (MD) for proportional and continuous variables, respectively, with 95% confidence interval (CI) and a P value of <0.05 considered statistically significant. Results: The search strategy yielded 117 articles. Four studies with 705 total patients were finalized comparing VC to placebo/sham treatment. The pooled complete spontaneous bowel movement (CSBM), defined as bowel movement without use of laxatives within the last 48 hours with sense of complete evacuation did not achieve statistical improvement with VC (MD =0.153; 95% CI: -0.218 to 0.523; P=0.422). However, spontaneous bowel movement (SBM), defined as bowel movement without use of laxatives within the last 48 hours, showed statistical improvement with VC (MD =0.159; 95% CI: 0.095 to 0.223; P<0.001). VC didn't show an increase in pooled adverse events (OR =1.431; 95% CI: 0.702 to 2.916; P=0.324). Conclusions: The systematic review and meta-analysis suggest that VC is safe and efficacious in some outcomes, however, larger randomized controlled trials (RCTs) and real-world data are needed to establish this.

Colonic Resection in an 8-Year-Old Girl with Intractable Functional Constipation and Diffuse Colonic Dysmotility and Failed Antegrade Flushes.

Optimal surgical management of patients with intractable constipation and diffuse colonic motility is not well defined. We present a patient with such a history, who ultimately achieved successful surgical management of constipation through a stepwise approach. An 8-year-old female presents with longstanding constipation and diffuse colonic dysmotility demonstrated with colonic manometry. She initially underwent sigmoid resection and cecostomy which failed and required diverting ileostomy. We initially proceeded with an extended resection, colonic derotation (Deloyers procedure), and neo-appendicostomy (neo-Malone) which resulted in successful spontaneous stooling for 1 year. Her constipation recurred and she subsequently underwent completion colectomy with ileorectal anastomosis given that she previously demonstrated ability to stool independently. Six months from surgery the patient continues to stool daily with assistance of fiber and loperamide. This case highlights a stepwise surgical approach to managing constipation due to diffuse colonic dysmotility and demonstrates that diffuse dysmotility may benefit from an upfront subtotal resection; however, it is crucial to assess a patient's ability to empty their rectum prior.

Diagnóstico e abordagem terapêutica da constipação idiopática crônica: uma revisão de especialistas brasileiros / Diagnosis and management of chronic idiopathic constipation: a narrative review from a brazilian expert task force

ABSTRACT Background Chronic idiopathic constipation (CIC) is a condition that widely affects the global population, represents relevant healthcare resource utilization and costs, and impacts the individual's well-being. Objective To review the consensus of expert societies and published guidelines on the diagnosis and treatment of CIC in adults, seeking to assist reasoning and decision-making for medical management of patients with CIC and provide a practical reference material. Methods A Brazilian medical task force searched the scientific literature in the following electronic databases: MEDLINE/PubMed, SciELO, EMBASE and Cochrane, using the following descriptors: chronic constipation, diagnosis, management of chronic constipation. In addition, a review of articles on the mechanism of action, safety, and efficacy of therapeutic options available in Brazil was carried out. Results The diagnostic approach and the understanding of the pathophysiology present in CIC are essential items to indicate the appropriate therapy and to understand the ecosystem of the patient's needs. Conclusion CIC is a common condition in adults, occurring more frequently in the elderly and in women. Proper management is defined by detailed medical history and physical examination, together with appropriate therapeutics, regardless pharmacological or not, and depending on the best moment of indication. This way, the impact on quality of life is also optimized.

RESUMO Contexto A constipação idiopática crônica (CIC) é uma condição que afeta amplamente a população global, representa um grande custo econômico, causa substancial utilização de recursos em saúde e impacta o bem-estar do indivíduo. Objetivo Revisar os consensos de Sociedades de especialistas e diretrizes publicados sobre o diagnóstico e tratamento da CIC em adultos, buscando auxiliar o raciocínio e a tomada de decisão para a conduta médica frente ao paciente e oferecer um material prático de referência. Métodos Uma força tarefa médica brasileira realizou uma busca na literatura científica nas bases de dados eletrônicos Medline/PubMed, SciELO, Embase e Cochrane, tendo sido utilizados os seguintes descritores: chronic constipation, diagnosis, management of chronic constipation. Adicionalmente, foi realizada uma revisão de artigos sobre o mecanismo de ação, segurança e eficácia das opções terapêuticas disponíveis no Brasil. Resultados A abordagem diagnóstica e o entendimento da fisiopatologia presente na CIC são itens fundamentais para que seja indicada a terapêutica apropriada e seja compreendido o ecossistema de necessidades do paciente. Conclusão A CIC é uma condição comum em adultos, ocorrendo com maior frequência em idosos e mulheres. O manejo correto é definido pela anamnese e exame físico detalhados, juntamente com a terapêutica apropriada, independentemente de ser farmacológica ou não, conforme o melhor momento de indicação. Desta forma, o impacto na qualidade de vida também é otimizado.