Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: a prospective single-center experience with mid-term follow-up (with video).

BACKGROUND AND AIMS: Gastroparesis (GP) is a multifactorial disease associated with a large burden on the health care systems. Pyloric-directed therapies including gastric peroral endoscopic myotomy (G-POEM) can be effective in improving patient quality of life and symptom severity. We report on the safety and efficacy of G-POEM and its impact on the quality of life of patients managed at a large referral center. METHODS: Consecutive patients with confirmed GP referred for G-POEM due to failure of medical therapy were included. All patients were assessed at baseline and then at 1, 3, 6, and 12 and 24 months after G-POEM using validated symptom and quality of life instruments, including the Gastroparesis Cardinal Symptom Index (GCSI), Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), and 36-Item Short Form Survey (SF-36). Patients were evaluated before and 6 months after the procedure with EGD, 4-hour scintigraphy, and pyloric EndoFLIP. Technical success was defined as the ability to perform full-thickness pyloromyotomy. Clinical response was defined as an improvement of ≥1 point on GCSI. RESULTS: Fifty-two patients (median age, 48 years; range, 25-80 years, 88% female) underwent G-POEM between February 2018 and September 2020 for the following phenotypes: vomiting-predominant (n=30), dyspepsia-predominant (n=16), and regurgitation-predominant (n=6) GP. The technical success rate was 100%. Adverse events were noted in 3 of 52 patients (5.77%), and were all managed successfully endoscopically. Clinical response was achieved in 68%, 58%, and 48% of patients at 1-month, 6-month, and 12-month follow-up (P < .001, P < .001, and P < .01, respectively). When classified by the cause of GP, the clinical response rates were diabetic GP 64% (11 of 17), postsurgical GP 67% (6 of 9), and idiopathic GP 72% (13 of 18). A statistically significant improvement in PAGI-SYM scores was observed at 1, 3, 6, 12, and 24 months, in addition to significant improvement in several domains of SF-36. Mean 4-hour gastric emptying was reduced 6 months after G-POEM (10.2%) compared with baseline (36.5%, P < .001). We report a significant reduction in the number of emergency department visits and days spent in the hospital up to 24 months after G-POEM. CONCLUSIONS: G-POEM appears to be a safe and feasible treatment alternative for refractory GP with significant short-term and mid-term improvements in overall symptoms, quality of life scores, and health care utilization.

An emerging method to noninvasively measure and identify vagal response markers to enable bioelectronic control of gastroparesis symptoms with gastric electrical stimulation.

BACKGROUND: Gastric electrical stimulation (GES) can be a life-changing, device-based treatment option for drug-resistant nausea and vomiting associated with diabetic or idiopathic gastroparesis (GP). Despite over two decades of clinical use, the mechanism of action remains unclear. We hypothesize a vagal mechanism. NEW METHOD: Here, we describe a noninvasive method to investigate vagal nerve involvement in GES therapy in 66 human subjects through the compound nerve action potential (CNAP). RESULTS: Of the 66 subjects, 28 had diabetic GP, 35 had idiopathic GP, and 3 had postsurgical GP. Stimulus charge per pulse did not predict treatment efficacy, but did predict a significant increase in total symptom score in type 1 diabetics as GES stimulus charge per pulse increased (p < 0.01), representing a notable side effect and providing a method to identify it. In contrast, the number of significant left and right vagal fiber responses that were recorded directly related to patient symptom improvement. Increased vagal responses correlated with significant decreases in total symptom score (p < 0.05). COMPARISON WITH EXISTING METHOD(S): We have developed transcutaneous recording of cervical vagal activity that is synchronized with GES in conscious human subjects, along with methods of discriminating the activity of different nerve fiber groups with respect to conduction speed and treatment response. CONCLUSIONS: Cutaneous vagal CNAP analysis is a useful technique to unmask relationships among GES parameters, vagal recruitment, efficacy and side-effect management. Our results suggest that CNAP-guided GES optimization will provide the most benefit to patients with idiopathic and type 1 diabetic gastroparesis.

Successful Improvement of Pain Symptomatology in a Suspected Case of Cramp-Fasciculation Syndrome via Interventional Pain Treatment.

Peripheral nerve hyperexcitability (PNH) syndromes are a rare set of neuromuscular disorders that include cramp-fasciculation syndrome (CFS) and Isaacs syndrome (IS). Successful treatment of these diseases has been achieved with antiepileptic medications; however, chronic pain symptoms can persist. We provide a case report of a 25-year-old female who has suffered from painful severe muscle spasms and fasciculations since childhood. With CFS as our working diagnosis, a treatment regimen using interventional pain techniques, including sympathetic chain blocks, ketamine infusions, and trigger point injections, resulted in a significant decrease in the patient's chronic pain symptoms. This case offers a novel application of interventional pain procedures and may help further our understanding of PNH syndromes.

Effect of dosing interval on pharmacokinetics of fentanyl pectin nasal spray from a crossover study.

OBJECTIVE: To evaluate the effects of different dosing intervals on multiple-dose pharmacokinetics, and safety and tolerability of fentanyl pectin nasal spray (FPNS). METHODS: This was an open-label study in healthy volunteers. Five FPNS treatments (1 × 100 µg; 2 × 100 µg at 4-, 2-, and 1-hour intervals, and 8 × 100 µg consecutively) were administered to the right nostril, with a ≥ 3-day washout period. Blood samples were collected at predose and up to 1,440 minutes postdose. Plasma fentanyl concentrations were determined. Pharmacokinetic parameters-peak concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve (AUC)-were derived using noncompartmental method. For the two-dose regimens, pharmacokinetic parameters were compared between doses using a paired t-test with p < 0.05 as statistically significant. RESULTS: Thirteen subjects were enrolled and 10 completed the study. Median tmax was 10-15 minutes across five regimens. Cmax post the second dose significantly increased for 1-hour (p < 0.0001) and 2-hour (p < 0.001) but not 4-hour intervals (p = 0.462). C(max) and AUC(0-24) following 8 × 100 µg were approximately fivefold of those following 1 × 100 µg. Dizziness (11.9 percent) and somnolence (4.9 percent) were most common adverse events (AEs). 12.9 percent of patients discontinued due to AEs. CONCLUSIONS: FPNS exhibited consistently rapid t(max). When intervals between two doses were shorter, the difference in C(max) between the first and second dose was larger. All regimens of FPNS were well tolerated. Exposure reached a plateau after eight consecutive doses, suggesting potential limited absorption through the nasal mucosa.