Adverse events associated with device assisted hyoid and tongue base suspension for obstructive sleep apnea.

PURPOSE: Hyoid and tongue base suspension may treat obstructive sleep apnea (OSA). This study summarizes device-related adverse events associated with the AIRvance and AIRLIFT systems used for hyoid and tongue base suspension. MATERIALS AND METHODS: The U.S. Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database was queried for reports describing adverse events associated with hyoid or tongue base suspension from January 2012 to December 2022. RESULTS: 77 adverse events were identified. When performed separately, adverse events were equally as common with hyoid suspension as with tongue base suspension. More complications occurred postoperatively (51 [66.2 %]) than intraoperatively (26 [33.8 %]). The most reported adverse events were infection (23 [29.9 %]), broken screw (15 [19.5 %]), pain or discomfort (10 [13.0 %]), suture rupture (8 [10.4 %]), and dislodged screw (7 [9.1 %]). 10 infections required drainage or debridement; 12 required device explantation. CONCLUSIONS: The present study is the largest and most longitudinal review of adverse events associated with hyoid and tongue base suspension. Infection was the most common adverse event, and may require device explantation. While adverse events were most frequently attributed to device malfunction, broken screw, suture rupture, and broken needle were often attributed to operator error due to application of excessive force. Surgeon training to increase familiarity with hyoid and tongue base suspension may reduce adverse events caused by operator error. The MAUDE database is limited as a passive surveillance system. Standardized reporting may improve understanding of associated adverse events, enabling better informed comparisons between surgical treatment options for OSA.

Airway fires in otolaryngologic surgery: A database review.

PURPOSE: An estimated 34 % of reported operating room fires involve the airway. Despite the inherent risks in otolaryngologic surgery, education regarding prevention and management of airway fires is limited in graduate medical training. One contributing factor is a lack of reporting of such rare events in our literature. METHODS: The U.S. Food and Drug Administration's Manufacturer and User Facility Device Experience database was queried for reports of adverse events related to fires occurring during surgical procedures of the airway from January 1, 2010, to March 31, 2020. RESULTS: 3687 reports were identified and 49 unique reports of airway fire were included. Sustained fires were described in 16 (32.7 %) reports and 33 (67.3 %) described transient flares. 2 fires extended beyond the airway and 9 (18.4 %) were noted to have occurred at the start of the case. Fires were reported most commonly during tonsillectomy (n = 22 [44.9 %]), vocal fold excision (n = 5 [10.2 %]), and adenoidectomy (n = 4 [8.2 %]). 46 reports attributed flare initiation to a specific element of the fire triangle. 16 patient and 2 operator injuries were reported. Saline washing was utilized in 7 (14.3 %) cases overall. Patients were extubated immediately in 2 (12.5 %) of the 16 reports of sustained fires. 0 mortalities were reported. CONCLUSION: Airway fires were reported in a variety of upper airway procedures performed regularly by otolaryngologists. The triggering factor that led to fire was identified as a spark or char in about half of the reported cases, and only 2 reports described immediate removal of the endotracheal tube.

Complications associated with energy-based devices during thyroidectomy from 2010-2020.

Objective: Harmonic Focus (Ethicon, Johnson and Johnson, Cincinnati, OH, USA), LigaSure Small Jaw (Medtronic, Covidien Products, Minneapolis, MN, USA), and Thunderbeat Open Fine Jaw (Olympus, Japan) are electrosurgical instruments used widely in head and neck surgery. The study aims to compare device malfunctions, adverse events to patients, operative injuries, and interventions related to Harmonic, LigaSure, and Thunderbeat use during thyroidectomy. Methods: The US Food and Drug Administration's Manufacture and User Facility Device Experience (MAUDE) database was queried for adverse events associated with Harmonic, LigaSure, and Thunderbeat from January 2005 to August 2020. Data were extracted from reports pertaining to thyroidectomy. Results: Of the 620 adverse events extracted, 394 (63.5%) involved Harmonic, 134 (21.6%) LigaSure, and 92 (14.8%) Thunderbeat. The reported device malfunctions most frequently associated with Harmonic was damage to the blade (110 (27.9%)), LigaSure was inappropriate function (47 (43.1%)), Thunderbeat was damage to the tissue or Teflon pad (27 (30.7%)), respectively. Burn injury and incomplete hemostasis were the most commonly reported adverse events. The operative injury reported most frequently when using Harmonic and LigaSure was burn injury. No operator injuries were reported with Thunderbeat use. Conclusion: The most frequently reported device malfunctions were damage to the blade, inappropriate function, and damage to the tissue or Teflon pad. The most frequently reported adverse events to patients was a burn injury and incomplete hemostasis. Interventions aimed at improving physician education may help reduce adverse events attributed to improper use.

Systematic Review of Recurrence Rates of Benign Vocal Fold Lesions Following Surgery.

OBJECTIVES: Benign vocal fold lesions which include vocal fold nodules, polyps, cysts and other lesions often recur after surgery and require additional treatments. This systematic review of the current literature evaluated the effects of adjunctive therapies in addition to surgical resection on the recurrence rates of benign vocal fold lesions in adults. STUDY DESIGN: Systematic review. METHODS: A search using relevant keywords in electronic databases was conducted. Extracted data include author, year of publication, patient demographics, diagnostic approach, lesion type, surgical procedure, type of adjunctive therapy and the rates of recurrence. Descriptive statistics were performed on the collected data when appropriate. RESULTS: Eleven articles were identified with a total of 1085 patients. The total 1101 lesions studied included 591 (53.7%) polyps, 125 (11.4%) nodules, 146 (13.3%) cysts, 184 (16.7%) pseudocysts, 19 (1.7%) midfold masses, 18 (1.6%) sulcus vocalis and 18 (1.6%) varices. Besides surgery, adjunctive therapies included voice therapy, steroid injection and reflux medication. There were 141 reported lesion recurrences, with an average recurrence rate of 13.0%. The recurrence rate in studies with adjunctive therapies was 7.14%, and in studies with no adjunctive therapies it was 24.44%. CONCLUSIONS: Available evidence suggests that adjunctive therapies following surgery are associated with decreased lesion recurrence rates. However, due to differences in sample size, inconsistent reporting of lesion characteristics, heterogeneity of adjunctive therapies, variability in follow-up time across studies, and other factors, it is not possible to determine exactly which adjunctive therapies are of significant benefit and which lesion types may benefit the most.

Otolaryngology residency program websites in a socially distanced application cycle.

OBJECTIVE: To provide an updated evaluation of otolaryngology residency program websites during a socially distanced application cycle. Criteria were selected to evaluate for level of comprehensiveness, new content accommodating a virtual interview cycle, and stated commitment to diversity and inclusion. STUDY DESIGN: Review of otolaryngology residency program websites. SETTING: Online websites between December 2020 and January 2021. METHODS: Otolaryngology residency program websites were evaluated for selected criteria. Programs were categorized by geographic location, size, and Doximity rankings. Differences between groups were analyzed using Student's t-test and analysis of variance with a significance level of P < .05. RESULTS: 118 otolaryngology residency program websites contained a mean (SD) of 16.3 (4.7) of 31 criteria (52.6%). Fewer than one third included virtual/video tours of facilities or the surrounding area. Only 33% had a stated commitment to diversity and inclusion. There was no difference in number of criteria included when categorized by geographic location (P = .22). Larger programs (17.9 vs 14.5, P < .001) and programs ranked in the top 50 by Doximity (17.7 vs 15.2, P = .003) included a significantly greater number of criteria. CONCLUSION: While the comprehensiveness of otolaryngology residency program websites has improved, considerable room for improvement remains. Programs should strive to maintain updated websites that highlight training opportunities, program culture, and commitment to diversity and inclusion. Programs also should consider prioritizing the development of new online resources that may be especially useful to applicants during a virtual interview cycle.

Respiratory Function and Voice: The Role for Airflow Measures.

OBJECTIVE: To clarify the relationship between voice and respiratory function, and to understand the role for airflow measures in the evaluation of voice patients. METHODS: Literature searches of MEDLINE (Ovid) and Web of Science were performed on April 6, 2020, to include articles written in English that both discussed voice in relation to lower respiratory function and reported evaluation of airflow. Search strategies included the keywords voice, respiratory, airflow, and aerodynamic measures. Data were extracted from articles that met inclusion criteria. RESULTS: Twenty studies were included for review. Fourteen (70%) studies evaluated at least 1 spirometric respiratory measure, including Forced Vital Capacity, Forced Expiratory Volume in 1 second, and Forced Expiratory Flow. Other measures assessed included mean flow rate, mean peak airflow, phonatory airflow, inspiratory airflow, expiratory airflow, and phonation quotient. Notably, four studies which included pulmonary function tests (PFTs) as part of voice evaluation discovered previously undiagnosed respiratory disease in their study populations. CONCLUSION: This review confirms that respiratory function contributes significantly to voice and reveals that few studies have explored the role for airflow measures in clarifying this relationship. Including airflow measures such as PFTs in standard voice evaluation may allow recognition of underlying respiratory disease contributing to voice dysfunction. Further research is recommended to establish indications and diagnostic criteria for the use of PFTs in voice patients.

Adverse Events Associated With Ossicular Prostheses: Utility of a Federal Database.

OBJECTIVES: Ossicular prostheses have demonstrated utility in ossicular chain reconstruction, but their use also is associated with complications. This study aims to explore the utility of the U.S. Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database for the systematic analysis of complications associated with ossicular prostheses. It also summarizes adverse events to patients (AEPs) and device malfunctions (DMs) reported in the MAUDE database, and attempts to examine the consequences brought about by these events and to identify likely root causes. STUDY DESIGN: Retrospective analysis of the MAUDE database. METHODS: The MAUDE database was queried for reports from January 2010 to May 2020. Data were extracted from reports involving the use of ossicular prostheses. RESULTS: Seventy-three medical device reports, reports submitted to the Food and Drug Administration detailing suspected device-associated malfunctions, injuries, and deaths, involved ossicular prostheses and were included for analysis, from which 126 adverse events were extracted. Of these, 50 (39.7%) were AEPs, while 76 (60.3%) were DMs. The most common AEPs were foreign body and hearing loss, while the DMs reported most commonly were broken prosthesis and displaced prosthesis. Of the 76 DMs, 19 (25%) were attributed to mishandling by the operator, while 6 (7.9%) were due to a defective device. Broken prosthesis was the DM most commonly attributed to mishandling by the operator in 16 (32.7%) cases. CONCLUSION: Ossicular prostheses are used extensively for ossicular chain reconstruction, but also are associated with adverse events. The MAUDE database in its current form does not appear sufficient for the systematic review of adverse events associated with ossicular prostheses. A more standardized reporting format with clearly defined categories and inclusion of relevant variables might improve the quality of information provided by the MAUDE database.

The jaw-dropping costs of oral cavity cancer malpractice.

BACKGROUND: Medical litigation is different than it was 20 years ago due to changes in health care. This study provides an updated analysis of oral cavity malpractice litigation from the past two decades (2000-2010 and 2011-2019). METHODS: Verdict reviews from the Westlaw database were analyzed from January 2000 to August 2019. Data were collected and analyzed with the Statistical Package for the Social Sciences. RESULTS: Sixty-five lawsuits were evaluated across 24 states. Failure to diagnose was the most common allegation in both decades. Adjusting for inflation, the average amount awarded from 2000 to 2010 was $1 721 068 and $3 925 504 from 2011 to 2019. CONCLUSIONS: There has been a significant rise in allegations of failure to biopsy and failure to refer (p < 0.05). In addition, while award amounts appear different between decades, the difference is not statistically significant (p = 0.248). Education should focus on early diagnosis, biopsy, and referral to physicians who routinely care for this patient population.

Predictive clinical exam findings in post-tonsillectomy hemorrhage.

OBJECTIVES: Post tonsillectomy hemorrhage (PTH) is a common complication of tonsillectomy. Our objectives were to: 1) Examine the postoperative course of patients presenting to St. Christopher's Hospital for Children (SCHC) with PTH; 2) Compare patients with and without a blood clot visualized in the tonsillar fossa at time of presentation to determine if outcomes regarding return to the operating room (OR) differ. METHODS: This was a retrospective chart review conducted at an academic, tertiary, pediatric hospital in an urban setting. Pediatric patients who underwent a tonsillectomy with concurrent adenoidectomy and were admitted for observation following secondary post tonsillectomy hemorrhage were reviewed. The effects of age, gender, indication, and clinical exam findings on admission on the rate of eventual return to the OR for control of hemorrhage were also analyzed. Chi-square analysis and Fisher's exact test were used to compare the significance of categorical frequencies. RESULTS: The rate of blood clot presence in our cohort was 50.9% (28/55). Return to OR rates were defined as patients who began actively hemorrhaging following admission for observation, further stratified by presence or absence of clot on admission physical exam. There was a statistically significant higher rate of return to OR in patients who presented with a clot (46.6%) on clinical exam versus no clot (18.5%) after resolved post tonsillectomy hemorrhage (p < .027). Furthermore, patients with a blood clot present were significantly more likely to require OR sooner (21.31 h from admission) than those without a clot (100.75 h from admission) (p < .012). There was no statistically significant higher rate of blood clot presence or rate of return to OR in groups based on age, gender, or indication. DISCUSSION: Pediatric patients presenting after resolved secondary PTH with a blood clot visualized in the tonsillar fossa are more likely to require return to the OR for hemostasis and cautery than are those without a blood clot, and this is more likely to occur within 24 h of admission. Thus, patients with a blood clot on initial presentation may benefit from admission for a 24-h observation period, while a similar observation period may be unproductive for patients without a blood clot. CONCLUSIONS: Patients who present with a resolved secondary PTH and a blood clot present on clinical exam require return to the OR more often than patients presenting without a blood clot. While previously controversial, we feel that this demonstrates that a 24-h observation of a patient with a clot on exam is reasonable.

Tracheotomy in COVID-19 Patients: A Systematic Review and Meta-analysis of Weaning, Decannulation, and Survival.

OBJECTIVES: A systematic review and meta-analysis was conducted to determine the cumulative incidences of decannulation and mechanical ventilation weaning in patients with coronavirus disease 2019 (COVID-19) who have undergone a tracheotomy. Weighted average mean times to tracheotomy, to decannulation, and to death were calculated from reported or approximated means. DATA SOURCES: PubMed, SCOPUS, CINAHL, and the Cochrane library. REVIEW METHODS: Studies were screened by 3 investigators independently. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Studies including patients with COVID-19 who underwent a tracheotomy were identified. Studies without reported mechanical ventilation weaning or decannulation were excluded. Data were pooled using a random-effects model. RESULTS: After identifying 232 unique studies, 18 articles encompassing outcomes for 3234 patients were ultimately included for meta-analysis, with a weighted mean follow-up time of 28.6 ± 6.2 days after tracheotomy. Meta-analysis revealed that 55.0% of tracheotomized patients were weaned successfully from mechanical ventilation (95% CI, 47.4%-62.2%). Approximately 34.9% of patients were decannulated successfully, with a mean decannulation time of 18.6 ± 5.7 days after tracheotomy. The pooled mortality in tracheotomized patients with COVID-19 was 13.1%, with a mean time of death of 13.0 ± 4.0 days following tracheotomy. CONCLUSION: At the current state of the coronavirus pandemic, over half of patients who have required tracheotomies are being weaned off of mechanical ventilation. While 13.1% patients have died prior to decannulation, over a third of all tracheotomized patients with COVID-19 reported in the literature have undergone successful decannulation.

Complications associated with PlasmaBlade TnA during tonsillectomy and adenoidectomy from 2010 to 2020: A MAUDE study.

PURPOSE: The pulsed-electron avalanche knife (PEAK) PlasmaBlade TnA (Medtronic, n.d.) is a relatively new electrosurgical technology that is used widely in head and neck surgery (Medtronic Manuals, n.d.). This study aims to summarize device malfunctions, patient complications, and subsequent interventions related to PEAK PlasmaBlade TnA during tonsillectomy and adenoidectomy. MATERIALS AND METHODS: The US Food and Drug Administration's Manufacture and User Facility Device Experience database was queried for reports of PlasmaBlade TnA adverse events from June 6, 2009, to August 30, 2020. Data were extracted from reports pertaining to tonsillectomy with or without adenoidectomy. RESULTS: 128 reports were identified, from which 163 adverse events were extracted. Of these, 23 (14.6%) were related to patients, and 140 (85.4%) were related to device malfunction. The most frequently reported patient-related adverse event was a burn injury (17 [73.9%]). The most common device malfunctions were dislodgment of device component (39 [27.9%]), followed by tip ignition (32 [22.9%]), damaged tip or wire during operation (28 [20%]), and melted device (24 [17.1%]). CONCLUSIONS: PEAK PlasmaBlade TnA have demonstrated utility in tonsillectomy with or without adenoidectomy but are associated with adverse events. Interventions aimed at improving both physician and patient education may help reduce adverse events attributed to improper use. Further study is needed to clarify optimal approaches to education.

Adverse Events Associated With Laser Use in the Upper Airway.

OBJECTIVE: Surgical lasers are used extensively in head and neck surgery. Laser use in the upper airway offers many advantages but also presents risks to patients and operators that are not reported comprehensively. This study aims to summarize device malfunctions, patient complications, and subsequent interventions related to laser use in the upper airway. METHODS: The US Food and Drug Administration's Manufacturer and User Facility Device Experience database was queried for reports of surgical laser adverse events from January 2010 to March 2020. Data were extracted from reports pertaining to the upper airway. RESULTS: Sixty-two reports involving upper airway laser use in an operating room were identified, from which 95 events were extracted. Of these, 40 (42.1%) were adverse events to patients, 2 (2.1%) adverse events to operators, and 53 (55.8%) device malfunctions. Dislodgement of laser fiber in the airway (23 [57.5%]), burn (8 [20%]), and scar (5 [12.5%]) were the most common adverse events to patients. Two incidents of eye exposure through unfiltered microscope lenses were the only adverse events to operators. Fiber break (26 [49.1%]) and flare (12 [22.6%]) were the most common device malfunctions. DISCUSSION: Surgical lasers have demonstrated utility in head and neck surgery but are associated with risks. This study discusses adverse events and device malfunctions associated with airway laser surgery and emphasizes shortcomings in current reporting. IMPLICATIONS FOR PRACTICE: Standardized reporting and multi-institutional research are needed to better understand adverse events related to surgical laser use and to allow accurate estimation of their prevalence.

Complications associated with tracheoesophageal voice prostheses from 2010 to 2020: A MAUDE study.

PURPOSE: Tracheoesophageal puncture with voice prosthesis placement remains the gold standard for voice restoration following total laryngectomy, but may cause various complications. This study aims to summarize patient-related and device-related adverse events associated with tracheoesophageal puncture and voice prosthesis placement. MATERIALS AND METHODS: The U.S. Food and Drug Administration's Manufacturer and User Facility Device Experience database was queried for reports of adverse events related to tracheoesophageal puncture with voice prosthesis placement from January 1, 2010, to April 30, 2020. Data were extracted from reports pertaining to tracheoesophageal prostheses. RESULTS: Seventy-seven reports involving tracheoesophageal voice prostheses were identified, from which 111 adverse events were extracted. Of these, 58 (52.3%) were patient-related, while 53 (47.7%) were device-related. The most frequently reported patient-related adverse events were aspirated prosthesis (24 [41.4%]), foreign body during placement (11 [19.0%]), aspiration pneumonia (9 [15.5%]), and aspirated brush tip (8 [13.8%]). The most common device-related adverse events were detached brush tip (15 [28.3%]), leak (14 [26.4%]), and torn esophageal flange (11 [20.8%]). CONCLUSIONS: While tracheoesophageal puncture with voice prosthesis placement has revolutionized voice rehabilitation following total laryngectomy, the procedure may be associated with adverse events both at the time of placement and later. Interventions aimed at improving both physician and patient education may help reduce adverse events attributed to improper use. Further research is needed to clarify optimal approaches to education.

Surgical management and outcomes of accessory parotid gland neoplasms: A systematic review.

OBJECTIVE: To evaluate surgical approaches and outcomes associated with accessory parotid gland neoplasms. DATA SOURCES: MEDLINE, SCOPUS, and the Cochrane Central Register of Controlled Trials. REVIEW METHODS: A systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed. Studies were included if they reported surgical management and outcomes of patients with accessory parotid gland neoplasms. RESULTS: After screening 3532 records, 15 studies were included with a total of 187 patients. Benign tumors consisted of 61.5% of cases. External open, transoral, and preauricular endoscopic approaches were used for 82.3%, 11.3%, and 6.5% of cases, respectively. Accessory lobe resection alone, concurrent with partial parotidectomy, and concurrent with total parotidectomy were used in 54.8%, 43.0%, and 2.2% of cases, respectively. Complication rates were similar between histology groups (7.8% benign vs. 8.3% malignant, p = 0.82). Accessory lobe resection with concurrent partial parotidectomy had the lowest overall complication rate (6.3%). Resections limited to the accessory lobe were found to have an overall complication rate of 8.7%. CONCLUSION: The results offer an overview of the surgical management and complications for accessory parotid gland tumors. Overall surgical complication rates found in these case series may be lower for management of accessory gland tumors than rates available in the literature for tumors within the main parotid gland.

The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the pooled global prevalence of olfactory and gustatory dysfunction in patients with the 2019 novel coronavirus (COVID-19). DATA SOURCES: Literature searches of PubMed, Embase, and Scopus were conducted on April 19, 2020, to include articles written in English that reported the prevalence of olfactory or gustatory dysfunction in COVID-19 patients. REVIEW METHODS: Search strategies developed for each database contained keywords such as anosmia, dysgeusia, and COVID-19. Resulting articles were imported into a systematic review software and underwent screening. Data from articles that met inclusion criteria were extracted and analyzed. Meta-analysis using pooled prevalence estimates in a random-effects model were calculated. RESULTS: Ten studies were analyzed for olfactory dysfunction (n = 1627), demonstrating 52.73% (95% CI, 29.64%-75.23%) prevalence among patients with COVID-19. Nine studies were analyzed for gustatory dysfunction (n = 1390), demonstrating 43.93% (95% CI, 20.46%-68.95%) prevalence. Subgroup analyses were conducted for studies evaluating olfactory dysfunction using nonvalidated and validated instruments and demonstrated 36.64% (95% CI, 18.31%-57.24%) and 86.60% (95% CI, 72.95%-95.95%) prevalence, respectively. CONCLUSIONS: Olfactory and gustatory dysfunction are common symptoms in patients with COVID-19 and may represent early symptoms in the clinical course of infection. Increased awareness of this fact may encourage earlier diagnosis and treatment, as well as heighten vigilance for viral transmission. To our knowledge, this is the first meta-analysis to report on the prevalence of these symptoms in COVID-19 patients.

Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1.

Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)-associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress-associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy.Implications: Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This posits Sigma1 modulators as novel therapeutic agents in PD-L1/PD-1 blockade strategies that regulate the tumor immune microenvironment.Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/2/243/F1.large.jpg Mol Cancer Res; 16(2); 243-55. ©2017 AACR.