Availability of evidence and comparative effectiveness for surgical versus drug interventions: an overview of systematic reviews and meta-analyses.

OBJECTIVES: This study aims to examine the prevalence of comparisons of surgery to drug regimens, the strength of evidence of such comparisons and whether surgery or the drug intervention was favoured. DESIGN: Systematic review of systematic reviews (umbrella review). DATA SOURCES: Cochrane Database of Systematic Reviews. ELIGIBILITY CRITERIA: Systematic reviews attempt to compare surgical to drug interventions. DATA EXTRACTION: We extracted whether the review found any randomised controlled trials (RCTs) for eligible comparisons. Individual trial results were extracted directly from the systematic review. SYNTHESIS: The outcomes of each meta-analysis were resynthesised into random-effects meta-analyses. Egger's test and excess significance were assessed. RESULTS: Overall, 188 systematic reviews intended to compare surgery versus drugs. Only 41 included data from at least one RCT (total, 165 RCTs) and covered a total of 103 different outcomes of various comparisons of surgery versus drugs. A GRADE assessment was performed by the Cochrane reviewers for 87 (83%) outcomes in the reviews, indicating the strength of evidence was high in 4 outcomes (4%), moderate in 22 (21%), low in 27 (26%) and very low in 33 (32%). Based on 95% CIs, the surgical intervention was favoured in 38/103 (37%), and the drugs were favoured in 13/103 (13%) outcomes. Of the outcomes with high GRADE rating, only one showed conclusive superiority in our reanalysis (sphincterotomy was better than medical therapy for anal fissure). Of the 22 outcomes with moderate GRADE rating, 6 (27%) were inconclusive, 14 (64%) were in favour of surgery and 2 (9%) were in favour of drugs. There was no evidence of excess significance. CONCLUSIONS: Though the relative merits of surgical versus drug interventions are important to know for many diseases, high strength randomised evidence is rare. More randomised trials comparing surgery to drug interventions are needed.

Recurrent Nasopharyngeal Carcinoma and the Role of Surgery.

Recurrent nasopharyngeal carcinoma (rNPC) presents unique challenges as reirradiation comes with significant treatment-related morbidity in swallowing, middle ear function, and large-vessel integrity. Advances in endoscopic technology have made surgery for rNPC an increasingly viable option for select patients and may play a role in providing a better quality of life to patients with this challenging disease. In carefully selected patients, endoscopic and open surgical approaches may provide comparable disease control while mitigating long-term treatment-related morbidity.

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Otolaryngology Considerations of Pituitary Surgery: What an Endocrinologist Should Know.

Endoscopic endonasal skull base surgery is the preferred surgical approach for the management of pituitary adenomas. Perioperative management of pituitary lesions requires multidisciplinary care and typically includes a dual surgeon team consisting of a neurosurgeon and an otolaryngologist. The involvement of the otolaryngologist allows for a safe surgical approach with excellent intraoperative visualization of the tumor to enable an effective resection of the tumor by the neurosurgeon. Detection and treatment of sinonasal pathology is essential prior to surgery. Patients may experience sinonasal complaints following endoscopic transsphenoidal surgery, although this is typically temporary. Sinonasal care in the postoperative period can expedite recovery to baseline. Here we discuss the perioperative factors of endoscopic pituitary surgery that endocrinologists should be aware of, ranging from preoperative patient selection and optimization to postoperative care, with a particular emphasis on anatomic and surgical factors.

Reimbursement for Olfactory Testing: A Growing Need at a Unique Time in History.

This Viewpoint addresses the lack of reimbursement for olfactory testing, which is especially important in a time when the populations of older adults and patients with COVID-19­associated olfactory dysfunction have grown.

Availability of evidence and comparative effectiveness for surgical versus drug interventions: an overview of systematic reviews.

Objectives: To examine the prevalence of comparisons of surgery to drug regimens, the strength of evidence of such comparisons, and whether surgery or the drug intervention was favored. Design: Systematic review of systematic reviews (umbrella review). Data sources: Cochrane Database of Systematic Reviews (CDSR). Eligibility criteria and synthesis of results: Using the search term "surg*" in CDSR, we retrieved systematic reviews of surgical interventions. Abstracts were subsequently screened to find systematic reviews that aimed to compare surgical to drug interventions; and then, among them, those that included any randomized controlled trials (RCTs) for such comparisons. Trial results data were extracted manually and synthesized into random-effects meta-analyses. Results: Overall, 188 systematic reviews intended to compare surgery versus drugs. Only 41 included data from at least one RCT (total, 165 RCTs with data) and covered a total of 103 different outcomes of various comparisons of surgery versus drugs. A GRADE assessment was performed by the Cochrane reviewers for 87 (83%) outcomes in the reviews, indicating the strength of evidence was high in 4 outcomes (4%), moderate in 22 (21%), low in 27 (26%) and very low in 33 (32%). Based on 95% confidence intervals, the surgical intervention was favored in 38/103 (37%), and the drugs were favored in 13/103 (13%) outcomes. Of the outcomes with high GRADE rating, only one showed conclusive superiority (sphincterotomy was better than medical therapy for anal fissure). Of the 22 outcomes with moderate GRADE rating, 6 (27%) were inconclusive, 14 (64%) were in favor of surgery, and 2 (9%) were in favor of drugs. Conclusions: Though the relative merits of surgical versus drug interventions are important to know for many diseases, high strength randomized evidence is rare. More randomized trials comparing surgery to drug interventions are needed. Protocol registration: https://osf.io/p9x3j.

Surgeon Volume and Laryngectomy Outcomes.

OBJECTIVE: To examine the relationship between surgeon volume and operative morbidity and mortality for laryngectomy. DATA SOURCES: The Nationwide Inpatient Sample was used to identify 45,156 patients who underwent laryngectomy procedures for laryngeal or hypopharyngeal cancer between 2001 and 2011. Hospital and surgeon laryngectomy volume were modeled as categorical variables. METHODS: Relationships between hospital and surgeon volume and mortality, surgical complications, and acute medical complications were examined using multivariable regression. RESULTS: Higher-volume surgeons were more likely to operate at large, teaching, nonprofit hospitals and were more likely to treat patients who were white, had private insurance, hypopharyngeal cancer, low comorbidity, admitted electively, and to perform partial laryngectomy, concurrent neck dissection, and flap reconstruction. Surgeons treating more than 5 cases per year were associated with lower odds of medical and surgical complications, with a greater reduction in the odds of complications with increasing surgical volume. Surgeons in the top volume quintile (>9 cases/year) were associated with a decreased odds of in-hospital mortality (OR = 0.09 [0.01-0.74]), postoperative surgical complications (OR = 0.58 [0.45-0.74]), and acute medical complications (OR = 0.49 [0.37-0.64]). Surgeon volume accounted for 95% of the effect of hospital volume on mortality and 16%-47% of the effect of hospital volume on postoperative morbidity. CONCLUSION: There is a strong volume-outcome relationship for laryngectomy, with reduced mortality and morbidity associated with higher surgeon and higher hospital volumes. Observed associations between hospital volume and operative morbidity and mortality are mediated by surgeon volume, suggesting that surgeon volume is an important component of the favorable outcomes of high-volume hospital care. Laryngoscope, 133:834-840, 2023.

Chronic interleukin-13 expression in mouse olfactory mucosa results in regional aneuronal epithelium.

BACKGROUND: Olfactory dysfunction is highly associated with chronic rhinosinusitis with nasal polyps (CRSwNP), and the severity of loss has been linked with biomarkers of type 2 inflammation. The ability of dupilumab to rapidly improve the sense of smell prior to improvement in polyp size suggests a direct role of IL-4/IL-13 receptor signaling in the olfactory epithelium (OE). METHODS: We created a transgenic mouse model in which IL-13 is inducibly expressed specifically within the OE. Gene expression analysis and immunohistology were utilized to characterize the effect of IL-13 on the structure of the OE. RESULTS: After induction of olfactory IL-13 expression, there is a time-dependent loss of neurons from OE regions, accompanied by a modest inflammatory infiltrate. Horizontal basal cells undergo morphologic changes consistent with activation and demonstrate proliferation. Mucus production and increased expression of eotaxins is observed, with marked expression of Ym2 by sustentacular cells. DISCUSSION: Chronic IL-13 exposure has several effects on the OE that are likely to affect function. The neuronal loss is in keeping with other models of allergic type 2 nasal inflammation. Future studies are needed to correlate cellular and molecular alterations in olfactory cell populations with findings in human CRSwNP, as well as to assess olfactory function in behavioral model systems.

Cost comparison between open thyroid lobectomy and radiofrequency ablation for management of thyroid nodules.

BACKGROUND: There is an increasing array of treatment options for addressing clinically significant thyroid nodules, including radiofrequency ablation (RFA). While effective, the cost compared to alternative approaches has not been well elucidated. METHODS: This study involved a retrospective chart review, focusing on variable direct cost (VDC) of each procedure, from April 2016 to January 2020. We analyzed costs for 53 open lobectomies and 16 RFA procedures. RESULTS: Cost effectiveness depended on the simulated cost of the RFA probe. In comparison to open lobectomy, the VDC to perform RFA was $597 (19%) cheaper when the simulated probe cost was $1500 and $403 (13%) more expensive for a probe cost of $2500. Statistical significance was achieved for both these differences. CONCLUSIONS: If cost per RFA probe can be less than $2100-the break-even dollar amount between open lobectomy and RFA-there would be considerable cost savings for treating thyroid nodules.

Minimally Invasive Surgery in the United States, 2022: Understanding Its Value Using New Datasets.

INTRODUCTION: While minimally invasive surgery (MIS) has transformed the treatment landscape of surgical care, its utilization is not well understood. The newly released Nationwide Ambulatory Surgery Sample allows for more accurate estimates of MIS volume in the United States-in combination with inpatient datasets. MATERIALS AND METHODS: Multiple nationwide databases from the Healthcare Cost and Utilization Project (HCUP) were used: the Nationwide Ambulatory Surgery Sample and National Inpatient Sample. The volume of MIS and robotic procedures were calculated from 2016 to 2018. An online query system, HCUPNet, was queried for inpatient stays from 1993 to 2014. RESULTS: In 2017, 9.8 million inpatient major operating room procedures were analyzed, of which 11.1% were MIS and 2.5% were robotic-assisted, compared with 9.6 million inpatient operating room procedures (11.2% MIS and 2.9% robotic-assisted) in 2018. There were 10.6, 10.6, and 10.7 million ambulatory procedures in 2016, 2017, and 2018, respectively. Ambulatory MIS procedures showed an increasing trend across years, representing 16.9%, 17.4%, and 18%, respectively. HCUPNet data revealed an increase in inpatient MIS cases from 529,811 (8.9%) in 1993 to 1,443,446 (20.7%) in 2014. CONCLUSIONS: This study is the first to estimate national MIS volume across specialties in both inpatient and ambulatory hospital settings. We found a trend toward a higher proportion of MIS and robotic cases from 1997 to 2018. These data may help contribute to a more comprehensive understanding of MIS value within surgery and highlight limitations of current databases, especially when categorizing robotic cases on a national scale.

Etiology of sinonasal inverted papilloma: An update.

Objective: Sinonasal inverted papilloma (IP) and its clinical features have been widely studied, but there are few studies delving into its etiology and risk factors. A narrative review was conducted to summarize a contemporary understanding of the potential etiologies of IP, including immunologic/inflammatory, viral, genetic, and environmental causes. Study Design: Review. Methods: A MEDLINE search was conducted through August 11, 2021, focusing on studies investigating the etiology and risk factors for sinonasal IP and its malignant transformation. Results: High- and low-risk human papillomavirus have been connected with the formation of IP, but conflicting evidence exists regarding their role. Occupational and industrial exposures may also contribute to IP formation, while smoking may increase the odds of malignant progression. Exon 20 mutations in EGFR are an active area of research in IP with mixed evidence. Finally, several cell cycle and angiogenic factors such as Ki67, VEGF, and Akt/mTOR have been implicated in the development and progression of IP. Conclusion: There continues to be conflicting evidence around the development of IP, but significant progress has been made in recent years. Further study is needed for all these potential etiologies to elucidate risk factors and therapeutic strategies.

Taste receptors in chronic rhinosinusitus, what is the evidence? A systematic review.

BACKGROUND: Bitter and sweet taste receptors (T2Rs and T1Rs), respectively, are involved in the innate immune response of the sinonasal cavity and associated with chronic rhinosinusitis (CRS). Growing evidence suggests extraoral TRs as relevant biomarkers, but the current understanding is incomplete. This systematic review synthesizes current evidence of extraoral taste receptors in CRS. METHODS: PubMed, Embase, Cochrane, Web of Science, and Scopus were reviewed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines and included studies of genotypic and phenotypic T2R/T1R status in CRS patients. RESULTS: Twenty-two studies with 3845 patients were included. Seventeen studies evaluated genotype and 10 evaluated taste phenotypes. Four of 6 studies examining the haplotype distribution of the T2R, TAS2R38, demonstrated increased AVI/AVI haplotype ("nontaster") frequency in CRS. Meanwhile, 2 studies demonstrated decreased bitter sensitivity in CRS with nasal polyposis (CRSwNP), whereas 3 other studies reported decreased bitter sensitivity only in CRS without nasal polyposis (CRSsNP). Findings regarding sweet sensitivity were mixed. Three studies with cystic fibrosis patients (n = 1393) were included. Studies investigating the association between clinical outcomes and TAS2R38 alleles were limited, but the nonfunctional combination of AVI/AVI was associated with increased utilization of sinus surgery and, in CRSsNP patients, with poorer improvement of symptoms postoperatively. CONCLUSION: Both genotypic and phenotypic assessments of T2Rs suggest a potential association with CRS, particularly CRSsNP. However, limited evidence and mixed conclusions cloud the role of T2Rs in CRS. Future investigations should aim to increase diverse populations, broaden institutional diversity, examine T1Rs, and utilize uniform assessments.

Quality of Life Considerations in Endoscopic Endonasal Management of Anterior Cranial Base Tumors.

Considering quality of life (QOL) is critical when discussing treatment options for patients undergoing endoscopic endonasal skull base surgery (EESBS) for cancers at the base of the skull. Several questionnaires have been developed and validated in the last 20 years to explore QOL in this patient population, including the Anterior Skull Base Questionnaire, Skull Base Inventory, EESBS Questionnaire, and the Sino-Nasal Outcome Test for Neurosurgery. The Sino-Nasal Outcomes Test-22 and Anterior Skull Base Nasal Inventory-12 are other tools that have been used to measure sinonasal QOL in anterior cranial base surgery. In addition to pathology-related perturbations in QOL endoscopic surgical options (transsellar approaches, anterior cranial base surgery, and various reconstructive techniques) all have unique morbidities and QOL implications that should be considered. Finally, we look ahead to new and emerging techniques and tools aimed to help preserve and improve QOL for patients with anterior cranial base malignancies.

Development of immunosuppressive myeloid cells to induce tolerance in solid organ and hematopoietic cell transplant recipients.

Replacement of failed organs followed by safe withdrawal of immunosuppressive drugs has long been the goal of organ transplantation. We studied changes in the balance of T cells and myeloid cells in the blood of HLA-matched and -mismatched patients given living donor kidney transplants followed by total lymphoid irradiation, anti-thymocyte globulin conditioning, and donor hematopoietic cell transplant to induce mixed chimerism and immune tolerance. The clinical trials were based on a conditioning regimen used to establish mixed chimerism and tolerance in mice. In preclinical murine studies, there was a profound depletion of T cells and an increase in immunosuppressive polymorphonuclear (pmn) myeloid-derived suppressor cells (MDSCs) in the spleen and blood following transplant. Selective depletion of pmn MDSCs in mice abrogated mixed chimerism and tolerance. In our clinical trials, patients given an analogous tolerance conditioning regimen developed similar changes, including profound depletion of T cells and a marked increase in MDSCs in blood posttransplant. Posttransplant pmn MDSCs transiently increased expression of lectin-type oxidized LDL receptor-1, a marker of immunosuppression, and production of the T-cell inhibitor arginase-1. These posttransplant pmn MDSCs suppressed the activation, proliferation, and inflammatory cytokine secretion of autologous T-cell receptor microbead-stimulated pretransplant T cells when cocultured in vitro. In conclusion, we elucidated changes in receptors and function of immunosuppressive myeloid cells in patients enrolled in the tolerance protocol that were nearly identical to those of MDSCs required for tolerance in mice. These trials were registered at www.clinicaltrials.gov as #NCT00319657 and #NCT01165762.