Intraoperative Parathyroid Hormone Monitoring In Normohormonal Primary Hyperparathyroidism: How Low Do You Go?

OBJECTIVE: The primary goal of this study was to determine in patients with normohormonal primary hyperparathyroidism (NHHPT) what percent reduction in post-excision intraoperative parathyroid hormone (IOPTH) from baseline would yield a rate of cure comparable to that in patients with classical primary hyperparathyroidism (PHPT). METHODS: This is a retrospective cohort study of patients who underwent parathyroidectomy between July 2013 and February 2020. Demographic data, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHHPT were compared to those with classical PHPT. Subgroup analyses were performed. RESULTS: Of the 496 patients included in the study, 66 (13.3%) were of the normohormonal variant based on preoperative intact parathyroid hormone (PTH) levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the two normohormonal groups were not significantly different from their classical counterparts (98.4% and 100.0% vs. 97.1%, p = 1.000). The median percent decline in post-excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.6% and 80.4% compared to their respective controls at 87.3%, p = 0.011 and p = 0.001. Although the rate of multiglandular disease was higher in one of the normohormonal variant groups, this difference was due to a higher rate of double adenomas, not four-gland hyperplasia. CONCLUSION: Patients with NHHPT undergoing parathyroidectomy can expect cure rates similar to that in patients with classical PHPT. The results of this study indicate that achieving an 80% drop or more in IOPTH levels predicts a high likelihood of cure. This is true irrespective of whether the patient is deemed normohormonal based on preoperative or intraoperative testing. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2480-2484, 2024.

Surgical salvage of human papillomavirus-positive oropharyngeal cancer: Secondary analysis of a randomized controlled trial.

BACKGROUND: Survival outcomes are generally better for human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) than other forms of head and neck cancer. However, less is known about oncologic outcomes, late adverse events, and gastrostomy tube dependence associated with salvage surgery after the failure of definitive chemoradiation in patients with HPV+ OPSCC. METHODS: A secondary analysis of the Radiation Therapy Oncology Group 1016 randomized trial, which compared radiotherapy plus cetuximab to radiotherapy plus cisplatin in patients with HPV+ OPSCC, was performed. The oncologic and adverse event outcomes for patients who underwent salvage surgery were examined. RESULTS: Among the 805 patients who were assigned to treatment and were eligible for analysis, 198 developed treatment failure. Salvage surgery was required for 61 patients (7.6%), with 33 patients undergoing salvage surgery after locoregional failure (LRF) and 28 patients undergoing salvage neck dissection within the 20 weeks after treatment. Patients with LRF who underwent salvage surgery experienced improved overall survival in comparison with patients with LRF who did not undergo surgery (45% vs. 17% at 5 years after treatment; hazard ratio, 0.41; 95% confidence interval [CI], 0.23-0.74). Surgical salvage after LRF was associated with similar frequencies of late grade 3/4 dysphagia in comparison with LRF without surgery (24% [95% CI, 13%-41%] vs. 20% [95% CI, 12%-32%]; p = .64) and with similar gastrostomy tube dependence at 2 years (29% [95% CI, 15%-49%] vs. 13% [95% CI, 5%-28%]; p = .12). CONCLUSIONS: Salvage surgery in patients with HPV+ OPSCC is associated with favorable survival and adverse event outcomes.

Gastrostomy tube dependence and patient-reported quality of life outcomes based on type of treatment for human papillomavirus-associated oropharyngeal cancer: Systematic review and meta-analysis.

We examined the impact of treatment modality on gastrostomy tube dependence and patient-reported outcomes in human papillomavirus-associated oropharyngeal cancer (HPV-OPSCC). We performed systematic review and meta-analysis of functional outcomes 1-3 years after treatment. Twenty-three studies were included, reporting on 3127 patients treated for HPV-OPSCC. Gastrostomy tube dependence failed to show statistically significant difference between surgery with adjuvant therapy and chemoradiotherapy with cisplatin at 12 months (8.3% [95% CI: 3.1-15.9] vs. 4.2% [1.1-9.2], p = 0.37) and 24-36 months (10.5% [95% CI: 3.2-21.5] vs. 3.3% [2.0-4.9], p = 0.06). Surgery with adjuvant therapy was associated with worse University of Washington Quality of Life (UW-QOL) Swallowing (84 [95% CI: 80-88] vs. 89 [87-90], p = 0.03) and UW-QOL Overall scores (76 [95% CI: 72-80] vs. 84 [81-86], p = 0.001) compared to chemoradiotherapy with cisplatin at 12 months. Surgery with adjuvant therapy was associated with worse performance on certain measures of patient-reported swallow and overall function compared to chemoradiotherapy with cisplatin. Further randomized controlled trials are needed to directly compare functional outcomes after treatment for HPV-OPSCC.

Hyperparathyroidism subsequent to radioactive iodine therapy for Graves' disease.

BACKGROUND: The development of primary hyperparathyroidism (PHPT) after radioactive iodine (RAI) treatment for thyroid disease is poorly characterized. The current study is the largest reported cohort and assesses the disease characteristics of patients treated for PHPT with a history of RAI exposure. METHODS: A retrospective analysis comparing patients, with and without a history of RAI treatment, who underwent surgery for PHPT. RESULTS: Twenty-eight of the 469 patients had a history of RAI treatment, all for Graves' disease. Patients with a history of RAI exposure had similar disease characteristics compared to control; however, patients with a history of RAI treatment had a higher rate of recurrence (7.4% vs 1.2%, p = 0.012). CONCLUSION: PHPT in patients with a history of RAI treatment can be approached in the same manner as RAI naive PHPT patients; however, the risk of recurrence of PHPT in RAI exposed patients may be higher.

Diet Significantly Influences the Immunopathology and Severity of Kidney Injury in Male C57Bl/6J Mice in a Model Dependent Manner.

Diet is a leading causative risk factor for morbidity and mortality worldwide, yet it is rarely considered in the design of preclinical animal studies. Several of the nutritional inadequacies reported in Americans have been shown to be detrimental to kidney health; however, the mechanisms responsible are unclear and have been largely attributed to the development of diabetes or hypertension. Here, we set out to determine whether diet influences the susceptibility to kidney injury in male C57Bl/6 mice. Mice were fed a standard chow diet, a commercially available "Western" diet (WD), or a novel Americanized diet (AD) for 12 weeks prior to the induction of kidney injury using the folic acid nephropathy (FAN) or unilateral renal ischemia reperfusion injury (uIRI) models. In FAN, the mice that were fed the WD and AD had worse histological evidence of tissue injury and greater renal expression of genes associated with nephrotoxicity and monocyte infiltration as compared to mice fed chow. Mice fed the AD developed more severe renal hypertrophy following FAN, and gene expression data suggest the mechanism for FAN differed among the diets. Meanwhile, mice fed the WD had the greatest circulating interleukin-6 concentrations. In uIRI, no difference was observed in renal tissue injury between the diets; however, mice fed the WD and AD displayed evidence of suppressed inflammatory response. Taken together, our data support the hypothesis that diet directly impacts the severity and pathophysiology of kidney disease and is a critical experimental variable that needs to be considered in mechanistic preclinical animal studies.

Glucose or Altered Ceramide Biosynthesis Mediate Oxygen Deprivation Sensitivity Through Novel Pathways Revealed by Transcriptome Analysis in Caenorhabditis elegans.

Individuals with type 2 diabetes display metabolic abnormalities, such as hyperglycemia, increased free fatty acids, insulin resistance, and altered ceramide levels, that contribute to vascular dysfunctions and compromised oxygen delivery. Caenorhabditis elegans fed a glucose-supplemented diet or with altered ceramide metabolism, due to a hyl-2 mutation, are sensitive to oxygen deprivation (anoxia). Our experiments showed that the combination of these factors further decreased the anoxia survival. RNA-sequencing analysis was performed to assess how a glucose-supplemented diet and/or a hyl-2 mutation altered the transcriptome. Comparison analysis of transcripts associated with anoxia-sensitive animals [hyl-2(tm2031) mutation or a glucose diet] revealed 199 common transcripts encoded by genes with known or predicted functions involving innate immunity, cuticle function (collagens), or xenobiotic and endobiotic phase I and II detoxification system. Use of RNA interference (RNAi) to target gene products of the xenobiotic and endobiotic phase I and II detoxification system (UDP-glycosyltransferase and Cytochrome p450 genes; ugt-15, ugt-18, ugt-19, ugt-41, ugt-63, cyp-13A12, cyp-25A1, and cyp-33C8) increased anoxia survival in wild-type animals fed a standard diet. Anoxia sensitivity of the hyl-2(tm2031) animals was suppressed by RNAi of cyp-25A1 or cyp-33C8 genes. A glucose diet fed to the P0 hermaphrodite decreased the anoxia survival of its F1 embryos; however, the RNAi of ugt-63 and cyp-33C8 suppressed anoxia sensitivity. These studies provide evidence that the detoxification system impacts oxygen deprivation responses and that C. elegans can be used to model the conserved detoxification system.