An Office-Based, Point-of-Care Test Predicts Treatment Outcomes With Community-Based Pelvic Floor Physical Therapy in Patients With Chronic Constipation.

BACKGROUND & AIMS: Rectal evacuation disorders are common among constipated patients. We aimed to evaluate the accuracy of an investigational point-of-care test (rectal expulsion device [RED]) to predict outcomes with community-based pelvic floor physical therapy. METHODS: We enrolled patients meeting Rome IV criteria for functional constipation failing fiber/laxatives for more than 2 weeks. RED was inserted and self-inflated, and then time-to-expel was measured in a left lateral position. All patients underwent empiric community-based pelvic floor physical therapy in routine care with outcomes measured at 12 weeks. The primary end point was global clinical response (Patient Assessment of Constipation Symptoms score reduction, >0.75 vs baseline). Secondary end points included improvement in health-related quality-of-life (Patient Assessment of Constipation Quality of Life score reduction, >1.0) and complete spontaneous bowel movement frequency (Food and Drug Administration complete spontaneous bowel movement responder definition). RESULTS: Thirty-nine patients enrolled in a feasibility phase to develop the use-case protocol. Sixty patients enrolled in a blinded validation phase; 52 patients (mean, 46.9 y; 94.2% women) were included in the intention-to-treat analysis. In the left lateral position, RED predicted global clinical response (generalized area under the curve [gAUC], 0.67; 95% CI, 0.58-0.76]), health-related quality-of-life response (gAUC, 0.67; 95% CI, 0.58-0.77; P < .001), and complete spontaneous bowel movement response (gAUC, 0.63; 95% CI, 0.57-0.71; P < .001). As a screening test, a normal RED effectively rules out evacuation disorders (expected clinical response, 8.9%; P = .042). Abnormal RED in the left lateral position (defined as expulsion within 5 seconds or >120 seconds) predicted 48.9% clinical response to physical therapy. A seated maneuver enhanced the likelihood of clinical response (71.1% response with seated RED retained >13 seconds) but likely is unnecessary in most settings. CONCLUSIONS: RED offers an opportunity to disrupt the paradigm by offering a personalized approach to managing chronic constipation in the community (Clinicaltrials.gov: NCT04159350).

Utility of Anorectal Testing to Predict Outcomes With Pelvic Floor Physical Therapy in Chronic Constipation: Pragmatic Trial.

BACKGROUND & AIMS: We performed a clinical trial that aimed to inform the clinical utility of anorectal manometry (ARM) and balloon expulsion time (BET) as up-front tests to predict outcomes with community-based pelvic floor physical therapy as the next best step to address chronic constipation after failing an empiric trial of soluble fiber supplementation or osmotic laxatives. METHODS: We enrolled 60 treatment-naïve patients with Rome IV functional constipation failing 2 weeks of soluble fiber supplementation or osmotic laxatives. All patients underwent ARM/BET (London protocol) followed by community-based pelvic floor physical therapy. Outcomes were assessed at baseline and 12 weeks. The primary end point was clinical response (Patient Assessment of Constipation-Symptoms instrument). RESULTS: Fifty-three patients completed pelvic rehabilitation and the post-treatment questionnaire. Contemporary frameworks define dyssynergia on balloon expulsion time and dyssynergic patterns (ARM), but these parameters did not inform clinical outcomes (area under the curve [AUC], <0.6). Squeeze pressure (>192.5 mm Hg on at least 1 of 3 attempts; sensitivity, 47.6%; specificity, 83.9%) and limited squeeze duration (inability to sustain 50% of squeeze pressure for >20 seconds; sensitivity, 71.4%; specificity, 58.1%) were the strongest predictors of clinical outcomes. Combining BET with squeeze duration (BET greater than 6.5 seconds and limited squeeze duration) improved predictive accuracy (AUC, 0.75; 95% CI, 0.59-0.90). BET poorly predicted outcomes as a single test (AUC, 0.54; 95% CI, 0.38-0.69). CONCLUSIONS: Using ARM to evaluate squeeze profiles, rather than dyssynergia, appears useful to screen patients with chronic constipation for up-front pelvic floor physical therapy based on likelihood of response. BET appears noninformative as a single screening test (ClinicalTrials.gov: NCT04159350).

Video-Based Deep Learning to Detect Dyssynergic Defecation with 3D High-Definition Anorectal Manometry.

BACKGROUND: We developed a deep learning algorithm to evaluate defecatory patterns to identify dyssynergic defecation using 3-dimensional high definition anal manometry (3D-HDAM). AIMS: We developed a 3D-HDAM deep learning algorithm to evaluate for dyssynergia. METHODS: Spatial-temporal data were extracted from consecutive 3D-HDAM studies performed between 2018 and 2020 at Dartmouth-Hitchcock Health. The technical procedure and gold standard definition of dyssynergia were based on the London consensus, adapted to the needs of 3D-HDAM technology. Three machine learning models were generated: (1) traditional machine learning informed by conventional anorectal function metrics, (2) deep learning, and (3) a hybrid approach. Diagnostic accuracy was evaluated using bootstrap sampling to calculate area-under-the-curve (AUC). To evaluate overfitting, models were validated by adding 502 simulated defecation maneuvers with diagnostic ambiguity. RESULTS: 302 3D-HDAM studies representing 1208 simulated defecation maneuvers were included (average age 55.2 years; 80.5% women). The deep learning model had comparable diagnostic accuracy [AUC 0.91 (95% confidence interval 0.89-0.93)] to traditional [AUC 0.93(0.92-0.95)] and hybrid [AUC 0.96(0.94-0.97)] predictive models in training cohorts. However, the deep learning model handled ambiguous tests more cautiously than other models; the deep learning model was more likely to designate an ambiguous test as inconclusive [odds ratio 4.21(2.78-6.38)] versus traditional/hybrid approaches. CONCLUSIONS: Deep learning is capable of considering complex spatial-temporal information on 3D-HDAM technology. Future studies are needed to evaluate the clinical context of these preliminary findings.

Gastroparesis and Severity of Delayed Gastric Emptying: Comparison of Patient Characteristics, Treatments and Medication Adverse Events.

BACKGROUND: Gastroparesis is a heterogeneous disorder. Patient characteristics and treatment responsiveness may differ based on the extent of delay in gastric emptying. AIMS: Characterize gastroparesis patients based on the degree of delay in gastric emptying, and assess the relationship of patient demographics, symptoms and response to therapy based on the extent of delay. METHODS: 1333 solid-phase 4-h scintigraphic gastric emptying scans were reviewed. Delayed emptying was categorized on percent retention at 4 h: mild (10-19%), moderate (20-29%), and severe (≥ 30%). Analyses were performed with regard to demographics, symptoms, esophagogastroduodenoscopy findings, medication use, and emergency department (ED) visits/hospitalizations. RESULTS: 284 patients had delayed gastric emptying: mild (42.6%), moderate (19.3%), and severe (37.3%). 79.5% were women, the mean age was 45 years (± 15), and mean symptom duration was 4.6 years (± 6.5). The main categories of gastroparesis were idiopathic and diabetes mellitus. The most commonly prescribed medications were metoclopramide, domperidone and erythromycin. Opiate use (n = 69) was associated with an increased degree of delayed gastric emptying (p = 0.03) with 50% of opiate users having very delayed gastric emptying. One-way analysis revealed that severely delayed gastric emptying correlated with both increased hospitalizations and ED visits. CONCLUSIONS: Severe delay in gastric emptying is a risk factor for increased hospitalizations and ED visits. Opiate use correlates with increased severity of gastric emptying. Identifying at-risk patients, stopping opioids, and instituting a programmatic care plan for patients with severely delayed gastric emptying may reduce ED visits, hospitalizations, and healthcare costs.

Gastroparesis: Medical and Therapeutic Advances.

Gastroparesis is a chronic, bothersome, and often disabling neuromuscular disorder of the upper gastrointestinal tract. The most frequently reported symptoms of gastroparesis include nausea, vomiting, epigastric pain, early satiety, and unintentional weight loss. Etiologies of gastroparesis include diabetes, connective tissue disorders, prior infection, mesenteric ischemia, and post-surgical complications. The largest category of gastroparesis patients is comprised of those in whom no definitive cause can be identified (idiopathic gastroparesis). The individual and societal burden of gastroparesis is substantial. It considerably reduces patients' quality of life accompanied by a significant negative impact to the healthcare system. The current treatments of gastroparesis are less than ideal. Dietary modification may improve symptoms in patients with mild disease. Metoclopramide is the only medication currently approved for the treatment of gastroparesis; however, it is associated with adverse effects in a sizable proportion of patients. Other medications are frequently employed to treat symptoms of nausea and vomiting, although technically all are used off-label since they are not FDA approved for the treatment of gastroparesis. These data highlight the need to identify novel, more effective treatment options for this disabling disease. This review will provide a brief synopsis on the epidemiology, etiology, and impact of gastroparesis, discussing new therapeutic advances.

Effectiveness of Intraoperative Versus Dedicated Islet Cell Laboratory Isolation for Total Pancreatectomy With Islet Autotransplant.

Background: Total pancreatectomy with islet autotransplantation (TPIAT) requires a complex islet isolation process of the explanted pancreas. Islet isolation has historically required a specialized laboratory to perform islet isolation. We report our experience with a novel technique of intraoperative islet isolation that does not require a specialized islet laboratory, thereby making the isolation process simpler, more accessible, and less costly. Methods: We performed a retrospective, comparative effectiveness analysis of 50 adult patients who underwent TPIAT from 2012 to 2020 (TPIAT with remote isolation [n = 20] versus intraoperative isolation of islet cells [n = 30]). The primary outcome was islet equivalents per body weight (IEQ/kg) for patients in each group. Results: Mean IEQ/kg's (4294 remote group versus 3015 intraoperative group, P = 0.06) and 1-y postoperative C-peptide levels (1.51 ng/mL remote group versus 0.91 ng/mL intraoperative group, P = 0.10) were not different between groups. Mean 1-y HbA1c levels (7.7% in the remote group versus 7.1% intraoperative group, P = 0.67) and 1-y insulin requirements (P = 0.31) were not statistically different. Lower average cost of hospitalization was seen in the intraoperative group, although this was not statistically significant ($104 398 remote versus $78 986 intraoperative, P = 0.81). Conclusions: Intraoperative islet isolation has similar effectiveness in regard to glycemic outcomes compared with the use of a dedicated islet cell isolation laboratory at a lower cost.

Symptomatic Management of Gastroparesis.

Gastroparesis is a chronic and debilitating neuromuscular disorder of the upper gastrointestinal tract. Symptoms of gastroparesis include nausea, vomiting, epigastric pain, early satiety, and weight loss. Treating gastroparesis can be difficult. Dietary changes may improve symptoms in patients with mild disease. A variety of medications can be used to treat symptoms of nausea and vomiting, although most have not been subjected to randomized controlled trials and only one is approved by the Food and Drug Administration (metoclopramide). Pain management is essential, as nearly 90% of patients report symptoms of epigastric pain. This article reviews treatment options for symptoms of gastroparesis.

The willingness of patients with gastroparesis to take risks with medications.

BACKGROUND: Gastroparesis has a significant negative impact on patients' quality of life. Only one medication is approved for gastroparesis and it is associated with a significant risk of side effects. AIM: To assess the willingness of patients to take risks associated with medications to treat gastroparesis symptoms. METHODS: We developed a questionnaire to assess medication risk-taking behaviour in patients identified as having documented gastroparesis (consistent symptoms, normal upper endoscopy, delayed gastric emptying). The survey assessed demographics, symptoms, medication use, anxiety, depression and impulsivity. A standard reference gamble evaluated respondents' willingness to take medication risks. RESULTS: Two hundred seven questionnaires were mailed to patients, 103 questionnaires were completed. Seventy-six percent were female; the mean age was 48 years; average duration of gastroparesis symptoms was 10 years. Self-reported symptom severity was severe in 52% and moderate in 32%. Gastroparesis patients reported that they would accept a median 13.4% risk of sudden death to cure their symptoms using a hypothetical medication. Self-reported gastroparesis symptom severity and Gastroparesis Cardinal Symptom Index scores correlated significantly with increased willingness to take risks associated with medications to treat gastroparesis, while anxiety was negatively associated. CONCLUSIONS: Gastroparesis patients are willing to accept markedly high risks with a hypothetical medication to cure their symptoms. Patients with severe gastroparesis symptoms and higher Gastroparesis Cardinal Symptom Index scores were more willing to take these risks. This study, the first to quantify gastroparesis patients' willingness to accept medication associated risks, should help clinicians through the complex maze of gastroparesis therapies and their associated risks and benefits.

Signet-Ring Cell Carcinoma Presenting as Hematochezia in a Patient with Crohn's Disease.

Signet-ring cell carcinoma is a rare adenocarcinoma, predominantly affecting the stomach and ovaries. Primary sites elsewhere are rarer. It is recognized that there is an increased cancer risk with the diagnosis of Crohn's disease. We report a patient with Crohn's disease who was diagnosed with signet-ring cell carcinoma in the setting of a Crohn's flare. Diagnosis was made with endoscopy. Treatment included laparoscopic-assisted right hemicolectomy with ileostomy with subsequent chemotherapy as an outpatient.