Balko, Ryan

AbstractBackgroundOpioid‐induced esophageal dysfunction (OIED) is a recognized complication of chronic opioid use. However, the impact of acute opioid administration on esophageal motility remains unclear.MethodsOpioid naïve patients with high‐resolution manometry (HRM) <480 min following esophagogastroduodenoscopy (EGD) (opioid‐HRM) and a control group with HRM <36 h prior to EGD between January 1, 2016, and November 10, 2018, from a single institution were identified. EGDs were performed exclusively with versed and fentanyl.Key ResultsOne hundred and seventy‐four patients were identified, with 83 (47.7%) opioid‐HRM and 91 (52.3%) controls. Mean time from EGD to HRM was 229 (78–435) min. Baseline clinical features and HRM indications were similar between opioid‐HRM and controls. Chicago classification v3.0 defined HRM findings were similar between groups. Major motility disorders as defined by the Chicago classification v3.0 occurred at a similar frequency among opioid‐HRM and controls (27.7% vs. 36.3%, p = 0.23). Mean distal contractile integrity (DCI) was higher in opioid‐HRM (1939.3 ± 1318.9 vs. 1792.2 ± 2062.3 mmHg∙cm∙s, p = 0.043), but maximum DCI, distal latency, and integrated relaxation pressure did not differ between groups. Subgroup analysis assessing time and dose dependency did not identify differences in individual manometric parameters and Chicago classification v3.0 diagnosis between patients with HRM <240 min after EGD, >240 min after EGD, ≥125 mcg of IV fentanyl, <125 mcg IV fentanyl and controls.Conclusions and InferencesSame‐day acute opioid administration did not affect HRM findings in opioid naïve patients. Studies assessing the pathophysiology of and duration‐dependent relationship with opioids in OIED are needed.

Abstract Background: Chemotherapy-induced peripheral neuropathy is characterized by pain, numbness, and tingling in the hands and feet and by diminished quality of life. Multiple previous studies, mostly preclinical, suggest that poly (ADP-ribose) polymerase (PARP) inhibitors may help with these symptoms. Objective: To assess the relationship between PARP inhibition and prevention/palliation of peripheral neuropathy in a clinical setting. Design: Meta-analysis of placebo-controlled clinical trials with PARP inhibitors. Setting/Subjects: We conducted 9 literature searches that included PubMed and other sources to compile fully published placebo-controlled clinical trials that tested PARP inhibitors and that reported on peripheral neuropathy. Measurements: The relative risks for neuropathy of all grades based on PARP inhibition were calculated for each trial. Each trial was weighted by its respective sample size. A forest plot was constructed. Results: Five trials, inclusive of 843 patients, met this study's eligibility criteria. Four included a concomitant PARP inhibitor (either olaparib or veliparib) and paclitaxel, a neuropathy-causing chemotherapy agent; the remaining trial evaluated long-term monotherapy with olaparib. The pooled overall relative risk for the development of neuropathy with PARP inhibition was 1.06 (95% confidence interval: 1–1.4). Conclusions: PARP inhibition does not appear to reduce the risk of chemotherapy-induced peripheral neuropathy. Whether PARP inhibitors may palliate (rather than prevent) neuropathy remains an area in need of further investigation.

Background: Paclitaxel-treated patients can suffer from years of peripheral neuropathy with pain, numbness, and tingling. Promising preclinical data with poly (ADP-ribose) polymerase (PARP) inhibitors led us to explore this class of agents to palliate this neuropathy. Methods: We relied on a completed trial that tested the antineoplastic effects of veliparib (NCT01012817). Data from patients who had been enrolled on NCT01012817, who previously received paclitaxel, and who had completed a validated pain assessment instrument were evaluated for improvement in their pain scores. Results: All 34 eligible patients were women, and all had a metastatic gynecological malignancy. On a 10-point scale (higher numbers indicative of worse pain), the average baseline score was 3.6 (range: 0-7). Seven patients (21%; 95% confidence interval: 9%-38%) manifested a drop in pain score (1 score lower than baseline followed by at least one consecutive value also below baseline). Of note, no patients initiated other therapy for neuropathy while on NCT01012817. Conclusion: The PARP inhibitors merit further study for chemotherapy-induced peripheral neuropathy. For patients suffering from peripheral neuropathy, these putative palliative effects might prompt earlier consideration of a PARP inhibitor as part of cancer treatment.