Patient perceptions underlying ctDNA molecular surveillance for HPV(+) oropharyngeal squamous cell carcinoma.

OBJECTIVE: Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC). METHODS: Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay. RESULTS: Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety. CONCLUSION: ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines.

Cutaneous fistula formation after thyroid nodule rupture: A rare complication after radiofrequency ablation.

BACKGROUND: With innovative treatment options such as radiofrequency ablation (RFA) for thyroid nodules, new complications are being identified. It is important to define and delineate complications in order to counsel patients appropriately about treatment options and their associated risks and benefits. METHODS: A 46-year-old male presented with a left thyroid nodule (6.5 cm). Fine needle aspiration results were benign. He started to develop intermittent dyspnea and underwent one RFA procedure. Approximately 6 days post-RFA, the neck area was raised and red with blister. The skin overlying the blister underwent eventual dehiscence with fluid spillage. Several months later, MRI imaging showed substernal extension with tracheal deviation. RESULTS: A left thyroid lobectomy was performed with cutaneous excision and successful closure of a fistula. CONCLUSIONS: This is the first reported case of a thyroid nodule rupture following RFA which manifested into a thyro-cutaneous fistula and required surgical intervention.

Does Long-Term Bowel Function Change After Colectomy for Colon Malignancy?

INTRODUCTION: Current understanding of bowel function after colectomy for colon cancer is informed by conflicting data, making preoperative patient counseling difficult. Our previous work demonstrates bowel movement frequency increases by postoperative follow-up, while overall function does not change. Long-term changes are unknown. We aimed to evaluate changes to patient-reported bowel function after colectomy for colon malignancy. METHODS: This is an observational study of patients that underwent colectomy for colon malignancy and completed the Colorectal Functional Outcome (COREFO) questionnaire at preoperative and 30-d postoperative clinic visits. Long-term bowel function was assessed using the same questionnaire via telephone or surveillance clinic visit. Mean domain and Total COREFO scores were compared baseline to long-term using paired t-tests. Quality of life analysis was obtained using the Patient Reported Outcome Measurement Information System-10 Global Health questionnaire for patients who completed this measure at surveillance visits or via telephone. RESULTS: Sixty-six patients met inclusion criteria. Median time between baseline and long-term questionnaire completion was 16 mo (interquartile range 11-30). Stool-related aspects (pain and bleeding with bowel movements, anal skin irritation) improved significantly from baseline to long-term. There were no other differences in any domain or Total COREFO score. Patient Reported Outcome Measurement Information System-10 scores demonstrated quality of life equivalent to the general US population. CONCLUSIONS: Over the long-term, after colectomy for colon cancer, patients report improvements in stool-related aspects (pain and bleeding with bowel movements, anal skin irritation). Evidence-based preoperative patient counseling should include these findings.

A Case of Left Carotid Artery Injury.

Invasive pituitary adenomas can infiltrate the dura mater, sphenoid sinus, or cranial bone. Endoscopic transsphenoidal sinus surgery is considered the standard of care; however, several potential complications must be noted. These complications can include cerebrospinal fluid leaks, infection, bleeding, optic nerve damage, and endocrinological complications such as diabetes insipidus. We present a case of a 69-year-old female with multiple recurrent invasive pituitary adenomas who has previously undergone 5 transsphenoidal procedures. Intraoperatively, the patient suffered from a left-sided carotid artery injury that was repaired with a muscle graft. Management of carotid artery injury during transsphenoidal surgery is optimized in a step-by-step approach which includes early recognition of the injury, briefing the surgical team, immediate control using compression, use of additional tissue graft for wound repair, and postoperative care. Through the use of the approach mentioned above, we were able to control the complication successfully.

Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system.

BACKGROUND: The comparative impact of histologic variants and grade has not been well described. METHODS: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival. RESULTS: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). CONCLUSION: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.

Regional Differences in Procedural Care of Hemorrhoid Management in Medicare Patients; Unwarranted Variation in Clinical Practice for a Medical-First Problem.

INTRODUCTION: Hemorrhoid disease is very common problem in the Medicare population. Prior work has shown significant variation in county-level practices of hemorrhoidectomy; however, regional variation of rubber band ligation (RBL) has yet to be assessed. This is important as many different practitioners from different specialties can perform this procedure repeatedly in an office-based setting. We aim to evaluate the variation of RBL and hemorrhoidectomy over a 7-y period. METHODS: Using Medicare part B claims data, we identified all beneficiaries >65 y seen for hemorrhoid disease between 2006 and 2013. Current Procedural Terminology (CPT) codes were used to identify all events for hemorrhoidectomy (46083, 46250, 46255, 46257, 46260, and 46261) or RBL (46221) by hospital referral region (HRR). We determined HRR-level rates of hemorrhoidectomy and RBL per 1000 beneficiaries adjusted for age, sex, and race. We calculated annual coefficients of variation (SD × 100/mean) for hemorrhoidectomy and RBL. RESULTS: 1.2 to 1.3 million fee-for-service Medicare beneficiaries were seen annually for evaluation of hemorrhoid disease. Mean-adjusted annual rates for hemorrhoidectomy by HRRs varied from 4.34 to 63.03 per 1000 beneficiaries. Mean-adjusted rates of RBL by HRRs varied from 7.06 to 163 per 1000 beneficiaries. Annual procedural coefficients of variation over the study period were 41-48 (high) for hemorrhoidectomy and 69-74 (very high) for RBL. CONCLUSIONS: While continued high variation exists for hemorrhoidectomy, there is very high variation for RBL between HRRs in treating hemorrhoid disease among Medicare beneficiaries. There are substantial Medicare expenditures in this high-volume population that are likely unwarranted.

A Near Miss of a Retropharyngeal Abscess with MRSA in a 5-Week-Old Boy Due to an Unusual Presentation.

A retropharyngeal abscess (RPA) in early childhood is not uncommon due to at-risk lymph nodes in this deep neck space and is typified by fever, odynophagia, and a constellation of respiratory manifestations. However, RPA is exceedingly rare in the neonatal subpopulation and not part of the usual differential diagnosis algorithm in this age range. Herein, we present a unique case of a previously healthy 5-week-old male infant with protracted "congestion" and difficulty in oral feeding, whose clinical course is confounded by intermittent, positional bradycardia and subsequent apnea. He was eventually diagnosed with a methicillin-resistant Staphylococcus aureus (MRSA) RPA, leading to concurrent vascular and airways compromise in the form of baroreceptor-mediated bradycardia from mass-effect carotid body compression. This clinical case is an important reminder that any infant with positional vital sign changes should prompt urgent and thorough investigation for extraordinary and otherwise uncommon pathophysiologic states. The case also highlights the power of multidisciplinary collaboration across multiple specialties and parental advocacy in unifying a diagnosis for rare pediatric illnesses.

Quantitative Evaluation of Aerosol Generation During In-Office Flexible Laryngoscopy.

Importance: Despite growing scientific knowledge and research, it is still unknown if office flexible laryngoscopy (FL) is aerosol generating and thereby potentially increases the risk of SARS-CoV-2 transmission. The limited literature that exists is conflicting, precluding formal conclusions. Objective: To determine whether FL is aerosol generating. Design, Setting, and Participants: This prospective cohort study included 134 patients seen in the otolaryngology clinic at a single tertiary care academic institution between February and May 2021. Two optical particle sizer instruments were used, quantifying particles ranging from 0.02 µm to 5 µm. Measurements were taken every 30 seconds, with sample periods of 15 seconds throughout the patient encounter. Instruments were located 12 inches from the patient's nares. Timing of events was recorded, including the start and end of physical examination, topical spray administration, start and end of laryngoscopy, and other potential aerosol-generating events (eg, coughing, sneezing). Data analysis was performed from February to May 2021. Exposures: Office examination and office FL. Main Outcomes and Measures: Bayesian online change point detection (OCPD) algorithm was used to detect significant change points (CPs) in this time-series data. The primary outcome was significant CP after FL compared with baseline physiologic variations, such as breathing and phonation. Results: Data were collected from 134 patients between February and May 2021. Ninety-one encounters involved FL. Of this group, 51 patients (56%) wore no mask over their mouth during FL. There was no statistically significant CP in either visits involving FL or visits where FL was not performed. Use of nasal spray did not result in CP in aerosol levels. Overall, neither the number of people present in the examination room, masks over patients' mouth, the duration of the visit, nor the duration of FL were associated with mean aerosol counts, regardless of the exposure. For larger aerosol sizes (≥1 µm), however, rooms with higher air exchange rates had significantly higher reductions in mean aerosol counts for visits involving FL. Conclusions and Relevance: The findings of this cohort study support that FL, including topical spray administration, is not a significant aerosol-generating procedure. The Bayesian OCPD model has a promising application for future aerosol studies in otolaryngology.

Radiofrequency ablation (RFA) compared to observation for benign thyroid nodules: emerging considerations for judicious use.

PURPOSE OF REVIEW: Radiofrequency ablation (RFA) for thyroid nodules confers tangible advantages over surgery, which include promising outcomes in the context of a minimally invasive procedure and the functional benefits of organ preservation. However, the ubiquity of benign nodules worldwide may spur the risk of misuse in cases where there is negligible gain over conventional surveillance. This review summarizes new developments in RFA and examines its judicious utilization in benign nodules. RECENT FINDINGS: RFA appears to be safe and effective for addressing compressive or cosmetic issues caused by benign functional and nonfunctional thyroid nodules. Volume regression occurs over 12 months, with some cases requiring multiple staged RFA procedures to achieve adequate shrinkage or to address regrowth. Complication rates including recurrent laryngeal nerve injury are reportedly low and are mitigated by strategic technical maneuvers, training, and experience. Consensus guidelines across international societies have emerged to better define appropriate patient candidates. Although association of overuse in analogous disciplines has been well established, no evidence of misuse in thyroid RFA has been described thus far. SUMMARY: Compelling multi-institutional data support RFA as first-line treatment for select benign thyroid nodules. Defining the nuances of patient selection and long-term surveillance are necessary to substantiate current observed results. Given the high incidence of thyroid nodules worldwide, it is important to emphasize that the majority of benign nodules will not require any intervention. Thorough consideration and careful implementation of recommended guidelines will hopefully lead to measurable benefit and avoid financial misuse.

SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination.

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-inducing agents, and SAMHD1 is recruited to DSBs. SAMHD1 complexes with CtIP via a conserved C-terminal domain and recruits CtIP to DSBs to facilitate end resection and HR. Significantly, a cancer-associated mutant with impaired CtIP interaction, but not dNTPase-inactive SAMHD1, fails to rescue the end resection impairment of SAMHD1 depletion. Our findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity.

Sirtuin 2 mutations in human cancers impair its function in genome maintenance.

Sirtuin 2 (SIRT2) is a sirtuin family deacetylase, which maintains genome integrity and prevents tumorigenesis. Although Sirt2 deficiency in mice leads to tumorigenesis, the functional significance of somatic SIRT2 mutations in human tumors is unclear. Using structural insight combined with bioinformatics and functional analyses, we show that naturally occurring cancer-associated SIRT2 mutations at evolutionarily conserved sites disrupt its deacetylation of DNA-damage response proteins by impairing SIRT2 catalytic activity or protein levels but not its localization or binding with substrate. We observed that these SIRT2 mutant proteins fail to restore the replication stress sensitivity, impairment in recovery from replication stress, and impairment in ATR-interacting protein (ATRIP) focus accumulation of SIRT2 deficiency. Moreover, the SIRT2 mutant proteins failed to rescue the spontaneous induction of DNA damage and micronuclei of SIRT2 deficiency in cancer cells. Our findings support a model for SIRT2's tumor-suppressive function in which somatic mutations in SIRT2 contribute to genomic instability by impairing its deacetylase activity or diminishing its protein levels in the DNA-damage response. In conclusion, our work provides a mechanistic basis for understanding the biological and clinical significance of SIRT2 mutations in genome maintenance and tumor suppression.

TNFRSF10C copy number variation is associated with metastatic colorectal cancer.

BACKGROUND: Genetic markers for distant metastatic disease in patients with colorectal cancer (CRC) are not well defined. Identification of genetic alterations associated with metastatic CRC could help to guide systemic and local treatment strategies. We evaluated the association of tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) copy number variation (CNV) with distant metastatic disease in patients with CRC using The Cancer Genome Atlas (TCGA). METHODS: Genetic sequencing data and clinical characteristics were obtained from TCGA for all available patients with CRC. There were 515 CRC patient samples with CNV and clinical outcome data, including a subset of 144 rectal adenocarcinoma patient samples. Using the TCGA CRC dataset, CNV of TNFRSF10C was evaluated for association with distant metastatic disease (M1 vs. M0). Multivariate logistic regression analysis with odds ratio (OR) using a 95% confidence interval (CI) was performed adjusting for age, T stage, N stage, adjuvant chemotherapy, gender, microsatellite instability (MSI), location, and surgical margin status. RESULTS: TNFRSF10C CNV in patients with CRC was associated with distant metastatic disease [OR 4.81 (95% CI, 2.13-10.85) P<0.001] and positive lymph nodes [OR 18.83 (95% CI, 8.42-42.09)]; P<0.001) but not MSI (OR P=0.799). On multivariate analysis, after adjusting for pathologic T stage, N stage, adjuvant chemotherapy, gender, and MSI, TNFRSF10C CNV remained significantly associated with distant metastatic disease (OR P=0.018). Subset analysis revealed that TNFRSF10C CNV was also significantly associated with distant metastatic disease in patients with rectal adenocarcinoma (OR P=0.016). CONCLUSIONS: TNFRSF10C CNV in patients with CRC is associated with distant metastatic disease. With further validation, such genetic profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive local therapies in patients with CRC, including radiation therapy for rectal adenocarcinoma.