Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation.

BACKGROUND: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C). AIM: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity. METHODS: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in both bloating and abdominal pain at Week 12. RESULTS: At baseline, 1104/1436 patients with IBS-C (76.9%) reported moderate-to-severe bloating. In the moderate-to-severe bloating subgroup, plecanatide significantly reduced bloating severity versus placebo (least-squares mean change [LSMC]: - 1.7 vs - 1.3; P = 0.002), reduced abdominal pain (- 1.7 vs - 1.3; P = 0.006), and increased CSBM frequency (1.4 vs 0.8; P < 0.0001). In the mild bloating subgroup, significant improvements were observed with plecanatide versus placebo for abdominal pain (LSMC: - 1.3 vs - 1.0; P = 0.046) and CSBM frequency (2.0 vs 1.2; P = 0.003) but not bloating (- 0.9 vs - 0.8; P = 0.28). A significantly greater percentage of patients were abdominal pain and bloating composite responders with plecanatide versus placebo (moderate-to-severe bloating: 33.6% vs 26.8% [P = 0.02]; mild bloating: 38.4% vs 27.2% [P = 0.03]). CONCLUSION: Plecanatide treatment improved IBS-C abdominal and bowel symptoms, including in those who present with moderate-to-severe bloating.

Step on the accelerator: modern treatment of constipation.

PURPOSE OF REVIEW: This review aims to explore effective management of constipation, examine challenges in making a positive diagnosis, and highlights the significance of a positive patient-provider relationship and emerging treatments. RECENT FINDINGS: Less than one-fifth of patients feel satisfied with treatment of their constipation. Sixty percent of patients with functional dyspepsia and gastroparesis have severe to very severe constipation that correlates with their upper gastrointestinal symptom severity. Two gold kiwifruits are noninferior to 10 g of psyllium in the treatment of constipation. More than 40% of patients undergoing lumbar fusion continue to fill opioid prescriptions 90 days after surgery, contributing to 80 000 chronic opioid users annually. Most patients are using over-the-counter (OTC) treatments for constipation with greater than 60% dissatisfied. Pharmacologic management involves the use of GCC agonists and emerging drug classes such as bile acid transport inhibitors and sodium hydrogen exchanger isoform 3 (NHE3) inhibitors. Nonpharmacologic treatments, including neuromodulation and FDA-approved vibrating capsule, show promise in improving symptoms and quality of life. SUMMARY: Constipation significantly impacts patients' quality of life and well being and the majority of patients are refractory to conservative measures and OTC treatments. Both pharmacologic and nonpharmacologic treatments hold promise for improving constipation and quality of life.

Evaluation of bidirectional gut-brain axis and anorectal function in Parkinson's disease with constipation.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative movement disorder with prodromal and highly prevalent gastrointestinal (GI) symptoms, especially constipation. Although PD models suggest gut-brain axis dysfunction, the mechanistic underpinnings and their correlation with GI symptoms are poorly understood. AIM: To examine the bidirectional gut-brain axis function in PD and correlate it with constipation severity, PD duration, and severity. METHODS: Rectal sensory thresholds and afferent cortical evoked potentials (CEP) were assessed using a 4-ring EMG electrode probe. Efferent anal and rectal motor evoked potentials (MEPs) were obtained following transcranial and lumbosacral magnetic stimulation. Bowel symptoms were assessed by prospective stool diary. The CEP and MEP latencies, rectal sensory thresholds, and anorectal sensorimotor data were compared between PD subjects and age-adjusted healthy subjects. KEY RESULTS: Twenty-five PD subjects with constipation (F/M = 6/19) and 20 healthy subjects (F/M = 14/6) were enrolled. The first and pain sensation thresholds were higher in PD subjects than healthy subjects (p < 0.002) but lost significance after adjustment for age. Age-adjusted rectal CEP and right-sided cortico-anal MEP latencies were prolonged in PD subjects compared to healthy subjects (p < 0.04). Also, half (4 of 8) age-adjusted spino-anal and rectal MEP latencies in PD subjects were significantly longer. In multivariate linear analysis, first rectal sensation and right-sided MEP latencies showed moderate correlation with constipation severity. CONCLUSIONS & INFERENCES: Parkinson's disease is associated with significant bidirectional gut-brain axis dysfunction as evidenced by prolonged afferent and efferent neuronal signaling. Constipation severity in PD is correlated to abnormal rectal sensation and lateralized disturbance of efferent brain-gut signaling.

Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation.

BACKGROUND: Patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS-C with severe constipation. METHODS: Data were analyzed post hoc from randomized, placebo-controlled trials (CIC [n = 2], IBS-C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5-point scale) or ≥8.0 (IBS-C; 11-point scale) during a 2-week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS-C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks). KEY RESULTS: Severe constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS-C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS-C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS-C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both). CONCLUSIONS AND INFERENCES: Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS-C.

Tenapanor in the Treatment of Irritable Bowel Syndrome with Constipation: Discovery, Efficacy, and Role in Management.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction (DGBI). IBS significantly impacts the quality of life of patients. Since its pathogenesis is unclear and can be multifactorial, it highlights the need for new and improved pharmaceutical drugs that not only improve bowel symptoms, but also address global IBS symptoms, such as abdominal pain. Tenapanor, a recently Food & Drug Administration (FDA)-approved medication for IBS with constipation (IBS-C), is a small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3) that inhibits the absorption of sodium and phosphate in the gastrointestinal tract, resulting in fluid retention and softer stool. Furthermore, tenapanor reduces intestinal permeability to improve visceral hypersensitivity and abdominal pain. Due to its recent approval, tenapanor was not included in the recent IBS guidelines, however, it may be considered for IBS-C patients failing first-line treatment of soluble fiber. In this review article, we aim to provide in-depth information to the reader regarding the design of tenapanor, its development through Phase I, II and III randomized clinical trials, and its role in the treatment of IBS-C.

Parkinson's Disease and Diabetes Mellitus: Synergistic Effects on Pathophysiology and GI Motility.

PURPOSE OF REVIEW: Parkinson's disease and diabetes affect an increasing proportion of the aging global population. Both conditions extensively affect gastrointestinal (GI) motility with similar and differing clinical symptoms. Nonetheless, GI symptoms in Parkinson's disease and diabetes pose significant morbidity and impairment of quality of life. Their pathophysiology is poorly understood, and therefore, effective treatment options are lacking. RECENT FINDINGS: Parkinson's disease patients have oropharyngeal dysphagia and constipation. They also have mild or absent upper GI symptoms associated with delayed gastric emptying, which is prevalent in 70% of patients. Delayed gastric emptying in Parkinson's disease leads to erratic medication absorption and fluctuating motor symptoms. Half of diabetics have upper GI symptoms, which correlate to gastric emptying and changes in brain activity of the insular cortex. The majority of diabetics also have constipation. Diabetics have an increased risk for developing Parkinson's disease and anti-diabetic medications are associated with risk reduction of developing Parkinson's disease. Hyperglycemia is associated with advanced glycated end products formation and acceleration of α-synuclein aggregation. GLP-1 receptor agonists have also demonstrated efficacy in improving motor symptoms and cognition in Parkinson's disease patients with diabetes. Parkinson's disease and diabetes are pan-enteric disorders with significant GI symptoms and impairment of gut motility. Both conditions have synergistic pathophysiologies that propagate neurodegenerative changes. Treatment options for GI symptoms in diabetic and Parkinson's disease patients are lacking. Anti-diabetic treatment improves motor symptoms in Parkinson's disease, however, its effect on GI symptoms is unclear.

Randomized Placebo-Controlled Phase 3 Trial of Vibrating Capsule for Chronic Constipation.

BACKGROUND & AIMS: Despite therapeutic advances, effective treatments for chronic constipation remain an unmet need. The vibrating capsule is a nonpharmacologic, orally ingested, programmable capsule that vibrates intraluminally to induce bowel movements. We aimed to determine the efficacy and safety of the vibrating capsule in patients with chronic constipation. METHODS: We conducted a phase 3, double-blind, placebo-controlled trial of patients with chronic constipation, who were randomized to receive either a vibrating or placebo capsule, once daily, 5 days a week for 8 weeks. The primary efficacy end points were an increase of 1 or more complete spontaneous bowel movements per week (CSBM1 responder) or 2 or more CSBMs per week (CSBM2) from baseline during at least 6 of the 8 weeks. Safety analyses were performed. RESULTS: Among 904 patients screened, 312 were enrolled. A greater percentage of patients receiving the vibrating capsule achieved both primary efficacy end points compared with placebo (39.3% vs 22.1%, P = .001 for CSBM1; 22.7% vs 11.4% P = .008 for CSBM2). Significantly greater improvements were seen with the vibrating capsule for the secondary end points of straining, stool consistency, and quality-of-life measures compared with placebo. Adverse events were mild, gastrointestinal in nature, and similar between groups, except that a mild vibrating sensation was reported by 11% of patients in the vibrating capsule group, but none withdrew from the trial. CONCLUSIONS: In patients with chronic constipation, the vibrating capsule was superior to placebo in improving bowel symptoms and quality of life. The vibrating capsule was safe and well tolerated. (Clinical trials.gov, Number: NCT03879239).

Dyssynergic Defecation and Other Evacuation Disorders.

Constipated patients are frequently referred to gastroenterologists for symptoms refractory to lifestyle modifications and laxatives. Dyssynergic defecation, the dyscoordination of rectoanal, abdominal, and pelvic floor muscles to facilitate defecation, is a major cause of refractory primary constipation. Understanding of the diagnosis, evaluation, and management of dyssynergic defecation and other evacuation disorders will allow providers to effectively manage these patients. This review focuses on the definition, pathophysiology, evaluation, and treatment of dyssynergic defecation and other evacuation disorders. Emerging treatments for these disorders include home biofeedback therapy for dyssynergic defecation and translumbosacral neuromodulation therapy for levator ani syndrome.

Translumbosacral Anorectal Magnetic Stimulation Test for Fecal Incontinence.

BACKGROUND: Neuropathy may cause fecal incontinence and mixed fecal incontinence/constipation, but its prevalence is unclear, partly due to the lack of comprehensive testing of spino-anorectal innervation. OBJECTIVE: This study aimed to develop and determine the clinical usefulness of a novel test, translumbosacral anorectal magnetic stimulation for fecal incontinence. DESIGN: This observational cohort study was conducted from 2012 to 2018. SETTINGS: This study was performed at a tertiary referral center. PATIENTS: Patients with fecal incontinence, patients with mixed fecal incontinence/constipation, and healthy controls were included. INTERVENTIONS: A translumbosacral anorectal magnetic stimulation test was performed by using an anorectal probe with 4 ring electrodes and magnetic coil, and by stimulating bilateral lumbar and sacral plexuses, uses and recording 8 motor-evoked potentials at anal and rectal sites. MAIN OUTCOME MEASURES: The prevalence of lumbar and/or sacral neuropathy was examined. Secondary outcomes were correlation of neuropathy with anorectal sensorimotor function(s) and morphological changes. RESULTS: We evaluated 220 patients: 144 with fecal incontinence, 76 with mixed fecal incontinence/constipation, and 31 healthy controls. All 8 lumbar and sacral motor-evoked potential latencies were significantly prolonged (p < 0.01) in fecal incontinence and mixed fecal incontinence/constipation groups compared with controls. Neuropathy was patchy and involved 4.0 (3.0) (median (interquartile range)) sites. Lumbar neuropathy was seen in 29% to 65% of the patients in the fecal incontinence group and 22% to 61% of the patients in the mixed fecal incontinence/constipation group, and sacral neuropathy was seen in 24% to 64% and 29% to 61% of these patients. Anal neuropathy was significantly more (p < 0.001) prevalent than rectal neuropathy in both groups. There was no correlation between motor-evoked potential latencies and anal sphincter pressures, rectal sensation, or anal sphincter defects. LIMITATIONS: No comparative analysis with electromyography was performed. CONCLUSION: Lumbar or sacral plexus neuropathy was detected in 40% to 75% of patients with fecal incontinence with a 2-fold greater prevalence at the anal region than the rectum. Lumbosacral neuropathy appears to be an independent mechanism in the pathogenesis of fecal incontinence, unassociated with other sensorimotor dysfunctions. Translumbosacral anorectal magnetic stimulation has a high yield and is a safe and clinically useful neurophysiological test. See Video Abstract at http://links.lww.com/DCR/B728. PRUEBA DE ESTIMULACIN MAGNTICA TRANSLUMBOSACRAL ANORECTAL PARA LA INCONTINENCIA FECAL: ANTECEDENTES:La neuropatía puede causar incontinencia fecal y una combinación de incontinencia fe-cal/estreñimiento, pero su prevalencia no está clara, en parte debido a la falta de pruebas comple-tas de inervación espino-anorrectal.OBJETIVO:Desarrollar y determinar la utilidad clínica de una nueva prueba, estimulación magnética trans-lumbosacral anorrectal para la incontinencia fecal.DISEÑO:Estudio de cohorte observacional del 2012 al 2018.ENTORNO CLINICO:Centro de referencia terciario.PACIENTES:Pacientes con incontinencia fecal, combinación de incontinencia fecal/estreñimiento y controles sanos.INTERVENCIONES:Se realizó una prueba de estimulación magnética translumbosacral anorrectal utilizando una sonda anorrectal con 4 electrodos anulares y bobina magnética, y estimulando los plexos lumbares y sacros bilaterales y registrando ocho potenciales evocados motores las regiones anal y rectal.PRINCIPALES MEDIDAS DE RESULTADO:Se examinó la prevalencia de neuropatía lumbar y/o sacra. Los resultados secundarios fueron la correlación de la neuropatía con las funciones sensitivomotoras anorrectales y cambios morfológi-cos.RESULTADOS:Evaluamos 220 pacientes, 144 con incontinencia fecal, 76 con combinación de incontinencia fe-cal/estreñimiento y 31 sujetos sanos. Las ocho latencias de los potenciales evocadas motoras lum-bares y sacras se prolongaron significativamente (p <0,01) en la incontinencia fecal y el grupo mixto en comparación con los controles. La neuropatía fue irregular y afectaba 4,0 (3,0) (mediana (rango intercuartílico) sitios. Se observó neuropatía lumbar en 29-65% en la incontinencia fecal y 22-61% en el grupo mixto, y neuropatía sacra en 24-64% y 29-61 % de pacientes respectivamen-te. La neuropatía anal fue significativamente más prevalente (p <0,001) que la rectal en ambos grupos. No hubo correlación entre las latencias de los potenciales evocadas motoras y las presio-nes del esfínter anal, la sensación rectal o los defectos del esfínter anal.LIMITACIONES:Sin análisis comparativo con electromiografía.CONCLUSIÓNES:Se detectó neuropatía del plexo lumbar o sacro en el 40-75% de los pacientes con incontinencia fecal con una prevalencia dos veces mayor en la región anal que en el recto. La neuropatía lumbo-sacra parece ser un mecanismo independiente en la patogenia de la incontinencia fecal, no asocia-do con otras disfunciones sensitivomotoras. La estimulación magnética translumbosacral anorrec-tal tiene un alto rendimiento, es una prueba neurofisiológica segura y clínicamente útil. Consulte Video Resumen en http://links.lww.com/DCR/B728.

Effects of Translumbosacral Neuromodulation Therapy on Gut and Brain Interactions and Anorectal Neuropathy in Fecal Incontinence: A Randomized Study.

OBJECTIVES: Translumbosacral neuromodulation therapy (TNT) improves symptoms of fecal incontinence (FI), but its mechanism of action is unknown. We tested the hypothesis that TNT at one or more frequency will significantly improve underlying pathophysiology of FI through modulation of ascending and/or descending signaling pathways in the gut and brain axis and anorectal sensorimotor function. MATERIALS AND METHODS: We assessed afferent anorectal-cortical evoked potentials (CEP) following electrical stimulation of anorectum, efferent cortico-anorectal and lumbo-anorectal and sacro-anorectal motor evoked potentials (MEP) after transcranial and lumbosacral magnetic stimulations, and anorectal manometry before and after six weekly TNT sessions in FI subjects, randomized to 1, 5, or 15 Hz repetitive magnetic stimulations. Neurophysiology, anorectal sensorimotor function, and symptoms were compared to examine mechanistic effects. Co-primary measures were ano-cortical CEPs, cortico-anal MEPs, and lumbosacral-anal MEPs. Baseline and post-treatment data were compared with Wilcoxon signed-rank test and changes between the three frequencies with one-way ANOVA. RESULTS: Thirty-three FI patients participated. After TNT, the afferent anal CEP latencies significantly decreased in the 1 Hz group compared to baseline (p = 0.0029) and 5 Hz or 15 Hz groups (p = 0.032). Cortico-anal MEPs were unchanged in all three groups. Bilateral lumbo-anal and sacro-anal MEP latencies significantly decreased with 1 Hz, lumbo-anal with 15 Hz, and sacro-anal with 5 Hz compared to baseline but without group differences. The 1 Hz group showed significant increase in anal squeeze sphincter pressure (p < 0.005) and maximum tolerable volume (p < 0.019) and demonstrated higher FI responder rate (p < 0.04) compared to the other two groups. The MEP responders were significantly correlated with FI responders (p = 0.006) in 1 Hz group. CONCLUSIONS: TNT significantly improves afferent ano-cortical signaling, efferent lumbo-anal and sacro-anal neuropathy and anorectal sensorimotor function. These neurobiologic effects were most prominent with 1 Hz frequency. TNT improves FI by modifying the underlying pathophysiology possibly through neuromodulation.

Randomized controlled trial of home biofeedback therapy versus office biofeedback therapy for fecal incontinence.

BACKGROUND: Biofeedback therapy is useful for treatment of fecal incontinence (FI), but is not widely available and labor intensive. We investigated if home biofeedback therapy (HBT) is non-inferior to office biofeedback therapy (OBT). METHODS: Patients with FI (≥1 episode/week) were randomized to HBT or OBT for 6 weeks. HBT was performed daily using novel device that provided resistance training and electrical stimulation with voice-guided instructions. OBT consisted of six weekly sessions. Both methods involved anal strength, endurance, and coordination training. Primary outcome was change in weekly FI episodes. FI improvement was assessed with stool diaries, validated instruments (FISI, FISS, and ICIQ-B), and anorectal manometry using intention-to-treat analysis. KEY RESULTS: Thirty (F/M = 26/4) FI patients (20 in HBT, 10 in OBT) participated. Weekly FI episodes decreased significantly after HBT (Δ ± 95% confidence interval: 4.7 ± 1.8, compared with baseline, p = 0.003) and OBT (3.7 ± 1.6, p = 0.0003) and HBT was non-inferior to OBT (p = 0.2). The FISI and FISS scores improved significantly in HBT group (p < 0.02). Bowel pattern, bowel control, and quality of life (QOL) domains (ICIQ-B) improved significantly in HBT arm (p < 0.023). Resting and maximum squeeze sphincter pressures significantly improved in both HBT and OBT groups and sustained squeeze pressure in HBT, without group differences. CONCLUSIONS & INFERENCES: Home biofeedback therapy is non-inferior to OBT for FI treatment. Home biofeedback is safe, effective, improves QOL, and through increased access could facilitate improved management of FI.

Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders.

BACKGROUND: Chronic constipation is a common, heterogeneous disorder with multiple symptoms and pathophysiological mechanisms. Patients are often referred to a gastroenterology provider after laxatives fail. However, there is limited knowledge of the spectrum and management of constipation disorders. AIM: To discuss the latest understanding of the spectrum of constipation disorders, tools for identifying a pathophysiologic-based diagnosis in the specialist setting, treatment options and the patient's perspective of constipation. METHODS: Literature searches were conducted using PubMed for constipation diagnostic criteria, diagnostic tools and approved treatments. The authors provided insight from their own practices. RESULTS: Clinical assessment, stool diaries and Rome IV diagnostic criteria can facilitate diagnosis, evaluate severity and distinguish between IBS with constipation, chronic idiopathic constipation and dyssynergic defecation. Novel smartphone applications can help track constipation symptoms. Rectal examinations, anorectal manometry and balloon expulsion, assessments of neuromuscular function with colonic transit time and colonic manometry can provide mechanistic understanding of underlying pathophysiology. Treatments include lifestyle and diet changes, biofeedback therapy and pharmacological agents. Several classes of laxatives, as well as prokinetic and prosecretory agents, are available; here we describe their mechanisms of action, efficacy and side effects. CONCLUSIONS: Constipation includes multiple overlapping subtypes identifiable using detailed history, current diagnostic tools and smartphone applications. Recognition of individual subtype(s) could pave the way for optimal, evidence-based treatments by a gastroenterology provider.

Translumbosacral Neuromodulation Therapy for Fecal Incontinence: A Randomized Frequency Response Trial.

INTRODUCTION: Treatments for fecal incontinence (FI) remain unsatisfactory because they do not remedy the underlying multifactorial dysfunction(s) including anorectal neuropathy. The aim of this study was to investigate the optimal dose frequency, clinical effects, and safety of a novel treatment, translumbosacral neuromodulation therapy (TNT), aimed at improving neuropathy. METHODS: Patients with FI were randomized to receive 6 sessions of weekly TNT treatments consisting of 600 repetitive magnetic stimulations over each of 2 lumbar and 2 sacral sites with either 1, 5, or 15 Hz frequency. Stool diaries, FI severity indices, anorectal neurophysiology and sensorimotor function, and quality of life were compared. Primary outcome measure was the change in FI episodes/week. Responders were patients with ≥50% decrease in weekly FI episodes. RESULTS: Thirty-three patients with FI participated. FI episodes decreased significantly (∆ ±95% confidence interval, 4.2 ± 2.8 (1 Hz); 2 ± 1.7 (5 Hz); 3.4 ± 2.5 (15 Hz); P < 0.02) in all 3 groups when compared with baseline. The 1 Hz group showed a significantly higher (P = 0.04) responder rate (91 ± 9.1%) when compared with the 5 Hz group (36 ± 18.2%) or 15 Hz (55 ± 18.2%); no difference was found between the 5 and 15 Hz groups (P = 0.667). Anal neuropathy, squeeze pressure, and rectal capacity improved significantly only in the 1 Hz (P < 0.05) group compared with baseline, but not in other groups. Quality of life domains improved significantly (P < 0.05) with 1 and 5 Hz groups. No device-related serious adverse events were noted. DISCUSSION: TNT significantly improves FI symptoms in the short term, and the 1 Hz frequency was overall better than 5 and 15 Hz. Both anorectal neuropathy and physiology significantly improved, demonstrating mechanistic improvement. TNT is a promising, novel, safe, efficacious, and noninvasive treatment for FI (see Visual Abstract, Supplementary Digital Content 3, http://links.lww.com/AJG/B598).

Dysphagia lusoria: A vascular etiology?

Dysphagia lusoria is difficulty swallowing as a result of extrinsic esophageal compression by an aberrant right subclavian artery (ARSA). We present the case of a 59-year-old patient with ARSA and history of chronic dysphagia. Vascular decompressive surgery was performed, but it failed to resolve his symptoms. Esophageal manometry indicated concomitant esophageal gastric junction outflow obstruction in the setting of a small hiatal hernia. Our case highlights the diagnostic dilemma surrounding dysphagia lusoria and identification of cases that should undergo surgical repair. Based on a thorough review of the literature and our case, we propose a complete foregut workup for possible other causes as potential etiologies of dysphagia prior to surgical treatment of dysphagia lusoria.