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The scientific topic of nanobiotechnology is one that is expanding quickly and has potential applications in the life sciences and human healthcare. Nanomedicine and biomedical nanotechnology both heavily rely on silver nanoparticles. Silver is a precious metal that naturally occurs, most frequently as part of a mineral resource in combination with other elements. With regard to various diseases, including bacteria, fungi, viruses, and yeast, silver nanoparticles have a natural antibacterial action. In the current investigation, Duranta erecta leaves were used in the manufacture of silver nanoparticles. The produced silver nanoparticles were studied using UV-VIS spectra, Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), and Fourier Transfer Infrared Spectra (FTIR). The produced silver nanoparticles from Duranta erecta leaves were tested using the nutrient agar disk diffusion technique by four bacterial species: E. coli, Streptococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa. UV-VIS Spectra were utilized to analyze the reduced silver ions and revealed a large resonance band at 410 nm. Through XRD, intense peaks and crystalline nanoparticle production were seen. TEM interpretation revealed spherical AgNPs in a range of diameters from 6 to 16 nm. All these gram-positive(S. aureus and B. subtilis) and gram-negative (E. Coli and P. aeruginosa) bacteria produce positive findings in the current investigation. [ABSTRACT FROM AUTHOR]

Reoperative parathyroid surgery (REOPS) is often associated with lower cure rates and greater risk of nerve injury and hypoparathyroidism. The aim of this study was to evaluate cure rates, pathology, complications, and the efficacy of preoperative localization in patients requiring REOPS. Between 1992 and 2017, 2491 consecutive patients underwent parathyroidectomy for primary hyperparathyroidism. With Institutional Review Board approval, our prospectively collected parathyroidectomy outcomes database was queried for operative findings, outcomes, pathology, and localization methodology. Three hundred forty-six patients had REOPS (111 men/32% and 235 women/68%), with an overall cure rate of 91 per cent and a mean follow-up of 1.9 ± 0.7 years. The average preoperative serum calcium and parathyroid hormone were 11 ± 1 mg/dL and 373 ± 796 pg/mL, respectively. Normalization of intraoperative parathyroid hormone occurred in 248 patients and it was predictive of cure in 98.8 per cent of patients. A single adenoma was resected in 253 patients (75%), and the superior gland location was most common at 57 per cent. Ectopic glands were identified in only 33 patients. When preoperative imaging localized a lesion, a tumor was identified in that location in 75.4 per cent of sestamibi or SPECT/CT scans, 57.8 per cent of CT, 61.2 per cent of MRI, and 46.2 per cent of US. When at least two imaging modalities were concordant, sensitivity improved to 91.6 per cent (P < 0.001). Complication rates of permanent hypoparathyroidism and recurrent nerve palsy occurred in 0.03 per cent of patients. REOP for recurrent or persistent primary hyperparathyroidism has a cure rate of 91 per cent. Most missed parathyroid tumors are in the neck, and multimodal imaging improves preoperative localization and success. [ABSTRACT FROM AUTHOR]

Introduction: Surgery remains the cornerstone treatment for gastric cancer. Previous studies have reported better lymphadenectomy with minimally invasive approaches. There is a paucity of data comparing robotic and laparoscopic gastrectomy in the US. Herein, we examined whether oncological adequacy differs between laparoscopic and robotic approaches. Methods: The National Cancer Database was utilized to identify patients who underwent gastrectomy for adenocarcinoma between 2010 and 2019. A propensity score-matching analysis between robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) was performed. The primary outcomes were lymphadenectomy ≥ 16 nodes and surgical margins. Results: A total of 11,173 patients underwent minimally invasive surgery for gastric adenocarcinoma between 2010 and 2019. Of those 8320 underwent LG and 2853 RG. Comparing the unmatched cohorts, RG was associated with a higher rate of adequate lymphadenectomy (63.5% vs 57.1%, p <.0.0001), higher rate of negative margins (93.8% vs 91.9%, p < 0.001), lower rate of prolonged length of stay (26.0% vs 29.6%, p <.0.001), lower 90-day mortality (3.7% vs 5.0%, p < 0.0001), and a better 5-year overall survival (OS) (56% vs 54%, p = 0.03). A propensity score-matching cohort with a 1:1 ratio was created utilizing the variables associated with lymphadenectomy ≥ 16 nodes. The matched analysis revealed that the rate of adequate lymphadenectomy was significantly higher for RG compared to LG, 63.5% vs 60.4% (p = 0.01), respectively. There was no longer a significant difference between RG and LG regarding the rate of negative margins, prolonged length of stay, 90-day mortality, rate of receipt of postoperative chemotherapy, and OS. Conclusions: This propensity score-matching analysis with a large US cohort shows that RG was associated with a higher rate of adequate lymphadenectomy compared to LR. RG and LG had a similar rate of negative margins, prolonged length of stay, receipt of postoperative chemotherapy, 90-day mortality, and OS, suggesting that RG is a comparable surgical approach, if not superior to LG. [ABSTRACT FROM AUTHOR]

Background: The incidence of hyperparathyroidism has increased in the USA. The previous work from our institution detected environmental chemicals (EC) within hyperplastic parathyroid tumors. The National Health and Nutrition Examination Survey (NHANES) is a program designed to assess the health status of people in the USA and includes measurements of EC in serum. Our aim was to determine which EC are associated with elevated parathyroid hormone (PTH) and calcium levels within NHANES. Methods: NHANES was queried from 2003–2016 for our analysis with calcium. A separate subgroup was queried from 2003–2006 that included PTH levels. Subjects with elevated calcium, and elevated PTH and normal Vitamin D levels were identified. Wilcoxon rank sum tests were used to analyze levels of EC in those with elevated calcium, and those with elevated PTH in the subgroup. All EC with p < 0.05 were then included in separate multivariate models adjusting for serum vitamin D and creatinine for PTH and albumin for calcium. Results: There were 51,395 subjects analyzed, and calcium was elevated in 2.1% (1080) of subjects. Our subgroup analysis analyzed 14,681 subjects, and PTH was elevated without deficient Vitamin D in 9.4% (1,377). Twenty-nine different polychlorinated biphenyls and the organochlorine pesticides hexachlorobenzene, transnonachlor, oxychlordane, and p,p'-dichlorodiphenyldichloroethylene (DDE) were found to be associated with elevated calcium and separately with elevated PTH (all p < 0.05). Conclusion: In NHANES, 33 ECs were found to be associated with elevated calcium as well as elevated PTH levels on our subgroup analysis. These chemicals may lead us toward a causal link between environmental factors and the development of hyperparathyroidism and should be the focus of future studies looking at chemical levels within specimens. [ABSTRACT FROM AUTHOR]

BACKGROUND: In this study by the International Collaborative Group, the authors examined a large cohort of patients accumulated from multiple institutions that had experience in craniofacial surgery with the objective of reporting outcomes and complications for craniofacial resection (CFR) in the elderly. METHODS: One hundred seventy patients aged ≥70 years were included in the study. The median age was 75 years (range, 70-98 years). One hundred four patients (61%) had received previous single-modality or combined treatment, which included surgery in 79 patients (46%), radiation in 47 patients (28%), and chemotherapy in 13 patients (8%). The most common histology was squamous cell carcinoma (67 patients; 39%). The margins of resection were close or microscopically positive in 56 patients (33%). Sixty-eight patients received adjuvant radiotherapy (40%), and 3 patients received chemotherapy (2%). Complications were classified into overall, local, central nervous system (CNS), systemic, and orbital. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were determined by using the Kaplan-Meier method. Outcomes were compared with patients aged <70 years. Statistical analyses for outcomes were performed in relation to patient characteristics, tumor characteristics (including histology and extent of disease), surgical resection margins, previous radiation, and previous chemotherapy to determine predictive factors. RESULTS: Postoperative mortality occurred in 16 patients (9%), and postoperative complications occurred in 72 patients (42%). Local wound complications occurred in 40 patients (24%), CNS complications occurred in 24 patients (14%), systemic complications occurred in 19 patients (11%), and orbital complications occurred in 4 patients (2%). Postoperative mortality and complications were significantly more frequent in elderly patients compared with patients aged <70 years (postoperative mortality: 9% vs 3%; P=.04; complications: 42% vs 32%; P=.0009). The 5- year OS, DSS, and RFS rates were significantly poorer than those for patients aged <70 years (OS: 42% vs 56%; P < .0001; DSS: 53% vs 61%; P=.04; RFS: 46% vs 54%; P=.03). Surgical margin status and primary tumor histology were independent predictors of OS, DSS, and RFS in multivariate analysis. CONCLUSIONS: CFR for malignant skull base tumors in elderly patients (aged ≥70 years) was associated with increased mortality, complications, and poorer outcomes compared with patients aged <70 years. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzed a large cohort of patients who underwent surgery for the treatment of skull base tumors. In the study, adjuvant radiotherapy was received by 35% of patients and chemotherapy was received by 10% of patients. The study found that the presence of positive/close margins was the only independent predictor of poor overall, recurrence-free, and disease-specific survival on multivariate analysis.

This article explores the growth rate and safety of observing pleomorphic adenomas (PAs) in pregnant patients. The study reveals that PAs in the parotid gland grow at a median rate of 4.6 mm/year, with potential acceleration during pregnancy and the post-partum period. All patients in the study chose to delay surgery until after pregnancy, and there were no significant complications to the mother or fetus. The study also found no evidence of malignant transformation in any of the cases. The authors conclude that pregnant patients with PAs can be safely monitored until surgery is necessary. The article emphasizes the challenges and considerations in managing benign parotid tumors in pregnant patients, highlighting the importance of comprehensive evaluation, quality imaging, and a reassuring cytologic report in determining the need for surgery. [Extracted from the article]

Purpose Of Review: The objective of this article is to critically review the rationale for the changes in the staging of the oral cavity cancers.Recent Findings: After reviewing many recent studies about oral cancer and analyzing multi-institutional data for outcomes, the staging system was updated to include new knowledge of the disease and its biological behavior.Summary: This article reviews the changes in the staging of oral cavity cancers published in the 8th edition of the AJCC/UICC TNM cancer staging manual and discusses future directions. [ABSTRACT FROM AUTHOR]

Background: The National Comprehensive Cancer Network guidelines recommend harvesting 16 or more lymph nodes for the adequate staging of gastric adenocarcinoma. This study examines the rate of adequate lymphadenectomy over recent years, its predictors, and its impact on overall survival(OS). Study design: The National Cancer Database was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006–2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression, Kaplan-Meier survival plots, and Cox proportional hazard regression were utilized. Results: A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Only 50.5% of the patients underwent a lymphadenectomy of ≥ 16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (p <.0001). The main independent predictors of adequate lymphadenectomy included high-volume facility with ≥ 31 gastrectomies/year (OR: 2.71; 95%CI:2.46–2.99), surgery between 2015–2019 (OR: 1.68; 95%CI: 1.60–1.75), and preoperative chemotherapy (OR:1.49; 95%CI:1.41–1.58). Patients with adequate lymphadenectomy had better OS than patients who did not: median survival: 59 versus 43 months (Log-Rank: p <.0001). Adequate lymphadenectomy was independently associated with improved OS (HR:0.79; 95%CI:0.77–0.81). Laparoscopic and robotic gastrectomies were independently associated with adequate lymphadenectomy compared to open, OR: 1.11, 95%CI:1.05–1.18 and OR: 1.24, 95%CI:1.13–1.35, respectively. Conclusion: Although the rate of adequate lymphadenectomy improved over the study period, a large number of patients still lacked adequate lymph node dissection, negatively impacting their OS despite multimodality therapy. Laparoscopic and robotic surgeries were associated with a significantly higher rate of lymphadenectomy ≥ 16 nodes. [ABSTRACT FROM AUTHOR]

PARPi-FL is a molecularly specific fluorescent agent that targets poly ADP-ribose polymerase 1, a DNA repair enzyme overexpressed in the nuclei of tumor cells. This imaging agent is being investigated in a clinical trial (NCT03085147) for the detection of oral cancer. The PARPi-FL mouthwash formulation currently being used in the phase I/II clinical trial comprises 1,000 nM of PARPi-FL dissolved first in 4.5 ml of polyethylene glycol (PEG) 300 and then in 9.5 ml of water. This formulation requires a 2-step process that can be cumbersome for routine clinical use. To minimize errors and simplify the formulation process, we have developed a new one-step formulation, which requires only the direct addition of water into a vial containing a mixture of the PARPi-FL and PEG 3350, which is also a powder. In a series of analytical and preclinical studies, we demonstrate that the new formulation of PARPi-FL is stable over 365 days, sustains its characteristics, and performs similar to the previous formulation. Moving forward, the new formulation of the PARPi-FL will be used for patients accrued in the phase II clinical trial. [ABSTRACT FROM AUTHOR]

Background. Human papillomavirus- (HPV-) associated oropharyngeal squamous cell carcinomas (OPSCCs) are clinically and pathologically distinct from HPV-negative tumors. Here, we explore whether HPV affects functional biomarkers, including γ H2AX, RAD51, and PARP1. Moreover, the role of [18F]PARPi as a broadly applicable imaging tool for head and neck carcinomas is investigated. Methods. HPV-positive and HPV-negative cell lines were used to evaluate the γ H2AX, RAD51, and PARP1 expression with immunoblotting and immunofluorescence. Effects of external beam ionizing radiation were investigated in vitro, and survival was investigated via colony-formation assay. [18F]PARPi uptake experiments were performed on HPV-negative and HPV-positive cell lines to quantify PARP1 expression. PARP1 IHC and γ H2AX foci were quantified using patient-derived oropharyngeal tumor specimens. Results. Differences in DNA repair were detected, showing higher RAD51 and γ H2AX expression in HPV-positive cell lines. Clonogenic assays confirm HPV-positive cell lines to be significantly more radiosensitive. PARP1 expression levels were similar, irrespective of HPV status. Consequently, [18F]PARPi uptake assays demonstrated that this tracer is internalized in cell lines independently from their HPV status. Conclusion. The HPV status, often used clinically to stratify patients, did not affect PARP1 levels, suggesting that PARP imaging can be performed in both HPV-positive and HPV-negative patients. This study confirms that the PET imaging agent [18F]PARPi could serve as a general clinical tool for oropharyngeal cancer patients. [ABSTRACT FROM AUTHOR]

Objective  This study was aimed to describe our institutional experience on characteristics and treatment outcomes of sinonasal sarcomas invading the anterior skull base. Design  Present study is a retrospective review. Setting  The study was conducted at an academic cancer care center. Participants  Thirty-one patients with skull base sarcomas treated with primary surgery from 1979 to 2015 were identified for this study from a preexisting database. Main Outcome Measures  Survival and recurrence outcomes using the Kaplan–Meier method were the focus areas of the study. Results  The median age was 44 years (range: 13–69 years). Twenty patients were male (64.5%). Twenty-nine patients underwent open craniofacial resection (93.5%) and two patients underwent endoscopic resection (6.5%). The majority of tumors were staged pT4 (77.4%). The most common pathologies were leiomyosarcoma (19.4%), osteosarcoma (16.1%), and chondrosarcoma (12.9%). Of those with known margin status, 10 patients had positive/close margins (32.2%) and 16 patients had negative margins (51.6%). Most tumors were high grade (74.2%). Twenty-three patients (74.2%) received adjuvant radiation and four patients (12.9%) received adjuvant chemotherapy. There were nine postoperative complications (29%) including one mortality and three cerebrospinal fluid leaks. There were 10 local, 2 regional, and 5 distant recurrences over a median follow-up of 74 months (range: 1–300 months). The 5-year disease-specific survival (DSS) was 69.8%. The 5-year locoregional recurrence-free probability (RFP) was 63.2% and the 10-year distant RFP was 71.7%. The 5-year DSS for high grade tumors was 64.2 and 85.7% for low grade tumors (p  = 0.117). Conclusion  This study contributes an updated analysis of anterior skull base sarcomas. Five-year DSS is approximately 70%. Analysis of survival outcomes based on grade, tumor size, and other factors is limited by small sample size and the rarity of these tumors. [ABSTRACT FROM AUTHOR]

Background: The approach for surgical treatment of patients with low-/intermediate-risk T1T2N0/Nx well-differentiated thyroid cancer (WDTC)—total thyroidectomy (TT) versus thyroid lobectomy (TL)—remains a controversial topic. Conducting a randomized controlled trial (RCT) would be the gold standard to address this issue. However, this is challenging due to excellent survival outcomes, and therefore, high number of patients and long-term follow-up would be required. As an alternative to RCT, we have used propensity score (PS) matching to determine if T1T2N0/Nx patients selected to have TL had equivalent outcomes to a similar group treated with TT. Methods: After institutional review board approval, a database of 6259 patients with WDTC treated with primary surgery at our institution between 1985 and 2016 was analyzed to identify patients with T1T2N0/Nx cancers. Of 3756 patients identified, 943 were managed by TL and 2813 by TT. To control for possible confounders and reduce potential bias, we selected age, sex, histology, 131I therapy, American Thyroid Association risk, and American Joint Committee Cancer stage as our PS matching criteria. Subsequently, 918 TL patients were successfully matched with 918 TT patients. The Pearson χ2 test or Fisher's exact test was used to compare categorical covariates, and Student's t-test was used for comparison of continuous variables between the two groups. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: After PS matching, there were no significant differences between TL and TT patients for OS (10-year OS: 92.2% vs. 91.3%, p = 0.9668), DSS (10-year DSS: 100% vs. 99.1%, p = 0.1967), or RFS (10-year RFS: 99.5% vs. 98.3%, p = 0.079). Conclusions: For low-/intermediate-risk patients with intrathyroidal thyroid cancer <4 cm, patients selected for TL have similar survival outcomes to a comparable group treated by TT. [ABSTRACT FROM AUTHOR]

Background: The American Thyroid Association guidelines recommend the routine use of radioactive iodine for remnant ablation (RRA) in all T3 or greater primary tumors, and selective use in patients with intrathyroidal disease >1 cm, or evidence of nodal metastases. The guidelines recognize that there is conflicting and inadequate data to make firm recommendations for most patients. The aim of this study was to analyze our institutional experience of the use of RRA in the management of papillary thyroid cancer, with a particular focus on outcomes for those patients selected not to receive RRA. Methods: We retrospectively reviewed 1129 consecutive patients who underwent total thyroidectomy at the Memorial Sloan-Kettering Cancer Center between 1986 and 2005. Of these, 490 were pT1-2 N0, 193 pT1-2 N1, and 444 pT3-4. Details on recurrence and disease-specific survival were recorded by the Kaplan-Meier method and compared using the log-rank test. Results: The five-year disease-specific survival and recurrence-free survival in the pT1/T2 N0, pT1-2 N1, and pT3-4 were 100% and 92%, 100% and 92%, and 98% and 87% respectively. Low-risk patients who were managed without RRA (who tended to have limited primary disease, pT1-2, and low-volume metastatic disease in the neck, pT1-2 N1-fewer than five nodes, all <1 cm greatest dimension) had five-year recurrence-free survival of >97%. In the group with advanced local tumors (pT3-4), those patients who did not receive RRA (who tended to have pT3 N0 disease) had five-year recurrence-free survival of >90%. Conclusion: Following appropriate surgical management, the majority of patients with low-risk local disease and even some patients with more advanced-stage (pT3) tumors or regional metastases have low rates of recurrence and high rates of survival when managed without RRA. [ABSTRACT FROM AUTHOR]

Background: Visual inspection and biopsy is the current standard of care for oral cancer diagnosis, but is subject to misinterpretation and consequently to misdiagnosis. Topically applied PARPi-FL is a molecularly specific, fluorescent contrast-based approach that may fulfill the unmet need for a simple, in vivo, non-invasive, cost-effective, point-of-care method for the early diagnosis of oral cancer. Here, we present results from a phase I safety and feasibility study on fluorescent, topically applied PARPi-FL. Twelve patients with a histologically proven oral squamous cell carcinoma (OSCC) gargled a PARPi-FL solution for 60 s (15 mL, 100 nM, 250 nM, 500 nM, or 1000 nM), followed by gargling a clearing solution for 60 s. Fluorescence measurements of the lesion and surrounding oral mucosa were taken before PARPi-FL application, after PARPi-FL application, and after clearing. Blood pressure, oxygen levels, clinical chemistry, and CBC were obtained before and after tracer administration. Results: PARPi-FL was well-tolerated by all patients without any safety concerns. When analyzing the fluorescence signal, all malignant lesions showed a significant differential in contrast after administration of PARPi-FL, with the highest increase occurring at the highest dose level (1000 nM), where all patients had a tumor-to-margin fluorescence signal ratio of >3. A clearing step was essential to increase signal specificity, as it clears unbound PARPi-FL trapped in normal anatomical structures. PARPi-FL tumor cell specificity was confirmed by ex vivo tabletop confocal microscopy. We have demonstrated that the fluorescence signal arose from the nuclei of tumor cells, endorsing our macroscopic findings. Conclusions: A PARPi-FL swish & spit solution is a rapid and non-invasive diagnostic tool that preferentially localizes fluorescent contrast to OSCC. This technique holds promise for the early detection of OSCC based on in vivo optical evaluation and targeted biopsy of suspicious lesions in the oral cavity. Trial registration: Clinicaltrials.gov—NCT03085147, registered on March 21st, 2017. [ABSTRACT FROM AUTHOR]

Background: Oral cancer is typically related to environmental carcinogen exposure including tobacco and alcohol. Other less investigated risk factors may be related to a suppressed or dysregulated immune state, and in oral cancer, various levels of immune dysregulation have been found to affect survival and recurrence rates. The rationale for this systematic review was to investigate the possible role that a growing chronic host condition like an autoimmune disease may play in this disease. Methods: A systematic search of the literature was carried out using four electronic databases in order to identify original research of any analytic study design type that investigated the relationship between autoimmune disease and oral cancer. Out of 1,947 identified records, 24 observational studies were included for qualitative synthesis. Results: The studies varied in end points ranging from overall survival (OS), standardized incidence ratio (SIR), and hazard ratio (HR). Due to the heterogenous sampling of studies even within the same study design group, a meta‐analysis was not employed. The current state of the literature is varied and heterogenous in both study design and endpoints. Conclusion: Major limitations existed introducing significant bias especially in determining cancer risk such as lack of information surrounding known etiologic risk factors such as alcohol and tobacco consumption. Despite these limitations, a signal was seen between autoimmune disease and oral cancer outcomes and risk. Future studies investigating the relationship between autoimmune disease and oral cancer in a more focused and quantitative manner are therefore needed. [ABSTRACT FROM AUTHOR]

Aims: The 8th edition of the American Joint Committee on Cancer (AJCC) Staging introduced depth of invasion (DOI) into the pT category of oral cavity squamous cell carcinoma. However, we noted multiple practical obstacles in accurately measuring DOI histologically in our daily practice. Methods and results: To compare the prognostic effects of DOI and tumour thickness (TT), a meticulous pathology review was conducted in a retrospective cohort of 293 patients with AJCC 7th edition pT1/T2 oral tongue squamous cell carcinoma. Overall survival (OS) and nodal metastasis rate at initial resection were the primary and secondary outcomes, respectively. We found that TT and DOI were highly correlated with a correlation coefficient of 0.984. The upstage rate was only 6% (18 of 293 patients) when using TT in the pT stage compared with using DOI. More importantly, DOI and TT, as well as pT stage using DOI and pT stage using TT, performed identically in predicting risk of nodal metastasis and OS. Conclusions: We therefore propose to replace DOI, a complicated measurement with many challenges, with TT in the pT staging system. [ABSTRACT FROM AUTHOR]

Objective.--Primary mucosal melanomas are rare tumors. We compare melanomas arising in 2 histologically different mucosa, the stratified oral squamous mucosa and pseudostratified sinonasal respiratory mucosa, to investigate the clinicopathologic influence of native mucosal histology on the tumor. Methods.--Clinicopathologic features of 36 melanomas arising in the squamous mucosa of the oral cavity were compared with 59 melanomas arising in the sinonasal respiratory mucosa. Results--The median age of patients was 61 and 63 years for oral and sinonasal melanomas, respectively, with the squamous and respiratory mucosa covering the maxilla being most frequently involved (68.7% and 66%, respectively). The former had a remarkable male predilection (28 men, 8 women), while the latter affected both sexes equally (29 men, 30 women). The oral melanomas were more likely to be detected in the early in situ or microinvasive stage (4 cases vs none, P = .008) and were more frequently amelanotic (14 vs 12, P = .049) than sinonasal melanomas. The sinonasal melanomas were frequently thicker (median thickness, 9 vs 2.6 mm), polypoid (29 vs none), ulcerated (57 vs 20), and necrotic (57 vs 14) than oral melanoma ( P < .001). Pseudopapillary architecture was more frequent in sinonasal melanomas (16 tumors vs none, P < .001), and desmoplastic melanomas were more frequent in the oral mucosa (6 vs 1, P = .005). Sinonasal melanoma showed vascular and deep tissue invasion more frequently than oral melanoma; however, no significant difference in disease-specific survival was noted (median survival, 2.8 years vs 3.0 years; 5-year survival, 37% vs 35%, respectively). Conclusion.--Sinonasal melanomas demonstrated aggressive morphologic features significantly more frequently than oral melanomas; however, prognosis remained similar in both groups. [ABSTRACT FROM AUTHOR]

Analyzes the occurrence of primary mucosal melanoma (MM) of the nasal cavity and paranasal sinuses in patients. Accountability for presence of malignant melanomas in nasal region; Etiology of the MM; Symptoms of mucosal melanoma; Diagnosis of the cancer.

Background. Human papillomavirus- (HPV-) associated oropharyngeal squamous cell carcinomas (OPSCCs) are clinically and pathologically distinct from HPV-negative tumors. Here, we explore whether HPV affects functional biomarkers, including γ H2AX, RAD51, and PARP1. Moreover, the role of [18F]PARPi as a broadly applicable imaging tool for head and neck carcinomas is investigated. Methods. HPV-positive and HPV-negative cell lines were used to evaluate the γ H2AX, RAD51, and PARP1 expression with immunoblotting and immunofluorescence. Effects of external beam ionizing radiation were investigated in vitro, and survival was investigated via colony-formation assay. [18F]PARPi uptake experiments were performed on HPV-negative and HPV-positive cell lines to quantify PARP1 expression. PARP1 IHC and γ H2AX foci were quantified using patient-derived oropharyngeal tumor specimens. Results. Differences in DNA repair were detected, showing higher RAD51 and γ H2AX expression in HPV-positive cell lines. Clonogenic assays confirm HPV-positive cell lines to be significantly more radiosensitive. PARP1 expression levels were similar, irrespective of HPV status. Consequently, [18F]PARPi uptake assays demonstrated that this tracer is internalized in cell lines independently from their HPV status. Conclusion. The HPV status, often used clinically to stratify patients, did not affect PARP1 levels, suggesting that PARP imaging can be performed in both HPV-positive and HPV-negative patients. This study confirms that the PET imaging agent [18F]PARPi could serve as a general clinical tool for oropharyngeal cancer patients. [ABSTRACT FROM AUTHOR]

Complete removal and negative margins are the goal of any surgical resection of primary oral cavity carcinoma. Current approaches to determine tumor boundaries rely heavily on surgeons' expertise, and final histopathological reports are usually only available days after surgery, precluding contemporaneous re-assessment of positive margins. Intraoperative optical imaging could address this unmet clinical need. Using mouse models of oral cavity carcinoma, we demonstrated that PARPi-FL, a fluorescent PARP inhibitor targeting the enzyme PARP1/2, can delineate oral cancer and accurately identify positive margins, both macroscopically and at cellular resolution. PARPi-FL also allowed identification of compromised margins based on fluorescence hotspots, which were not seen in margin-negative resections and control tongues. PARPi-FL was further able to differentiate tumor from low-grade dysplasia. Intravenous injection of PARPi-FL has significant potential for clinical translation and could aid surgeons in assessing oral cancer margins in vivo. [ABSTRACT FROM AUTHOR]

Background: Distant metastases (DMs) are the primary cause of treatment failure in patients with salivary gland carcinoma. There is no consensus on the standard treatment.Methods: Patients with DMs were identified from an institutional database of 884 patients with salivary gland cancer who underwent resection of the primary tumor between 1985 and 2015. Survival outcomes for patients with DMs were determined with the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with DM.Results: Of the 884 patients identified, 137 (15%) developed DMs during follow-up. Most of the primary tumors (n = 77 [56%]) were located in a major salivary gland. At clinical presentation, 53% of the tumors were classified as T3 or T4, and 32% had clinical node metastases. The median time to DM was 20.3 months. The factors associated with shorter distant recurrence-free survival were male sex, high-risk tumor histology, and advanced pathological T and N classifications. Patients with bone metastases had a lower survival rate than patients with lung metastases. The total number of DMs in a patient was inversely associated with survival. Patients who underwent surgical resection of DMs had a significantly higher 5-year rate of metastatic disease-specific survival than patients who underwent observation or nonsurgical treatment (44%, 29%, and 19%, respectively; P = .003).Conclusions: In patients with DMs of salivary gland carcinoma, survival is negatively associated with high-grade histology, bone DMs, and the total number of DMs. Metastasectomy can help to lengthen disease-free survival. [ABSTRACT FROM AUTHOR]

The evaluation of disease extent and post-therapy surveillance of head and neck cancer using 2-deoxy-2-18F]fluoro- d -glucose (18F]FDG) PET is often complicated by physiological uptake in normal tissues of the head and neck region, especially after surgery or radiotherapy. However, irrespective of low positive predictive values, 18F]FDG PET remains the standard of care to stage the disease and monitor recurrences. Here, we report the preclinical use of a targeted poly (ADP-ribose) polymerase1 (PARP1) binding PET tracer, fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor (18F]PARPi), as a potential alternative with greater specificity. Using an orthotopic xenograft mouse model injected with either FaDu or Cal 27 (human squamous cell carcinoma cell lines) we performed PET/CT scans with the 2 tracers and compared the results. Gamma counts and autoradiography were also assessed and correlated with histology. The average retained activity of 18F]PARPi across cell lines in tumor-bearing tongues was 0.9 ± 0.3%ID/g, 4.1 times higher than in control (0.2 ± 0.04%ID/g). Autoradiography and histology confirmed that the activity arose almost exclusively from the tumor areas, with a signal/normal tissue around a ratio of 42.9 ± 21.4. In vivo , 18F]PARPi-PET allowed delineation of tumor from healthy tissue (p <.005), whereas 18F]FDG failed to do so (p =.209). We demonstrate that 18F]PARPi is more specific to tongue tumor tissue than 18F]FDG. 18F]PARPi PET allows for the straightforward delineation of oral cancer in mouse models, suggesting that clinical translation could result in improved imaging of head and neck cancer when compared to 18F]FDG. [ABSTRACT FROM AUTHOR]

Background: Retropharyngeal lymph node metastases (RPMs) from differentiated thyroid carcinoma (DTC) are rare. Treatment includes surgical resection, radioactive iodine (RAI) therapy, or external beam radiation therapy (EBRT). The objective of this study was to describe our experience in the management of DTC-associated RPMs. Methods: Patients diagnosed with a DTC-associated RPM from 1999 to 2018 were identified at our institution, using key search terms in imaging and histology reports. Patient and tumor characteristics were recorded, and patients were grouped according to RPM management: observation, nonsurgical treatment, or surgical resection. The estimated rates of local RPM control, disease-specific survival (DSS), and distant metastasis-free probability (DMFP) were calculated by using the Kaplan-Meier method. Results: Of the 65 patients identified, 53 (82%) had an RPM as a manifestation of recurrent disease. Twenty-five patients (38%) underwent observation, 13 (20%) received nonsurgical treatment (RAI, EBRT, and/or systemic therapy), and 27 (42%) underwent surgical resection. In the observation cohort, all patients had a stable RPM, which in the majority (80%) of cases remained <1.5 cm during the period of observation (median 28 months). Of the 13 patients in the nonsurgical treatment cohort, 3 received RAI therapy, 7 received EBRT, and 3 received systemic therapy only. In the surgical cohort, the median RPM maximum diameter was 2.0 cm (range 0.8–4.2 cm). The size of the RPM was predictive of surgical resection versus observation (p < 0.001). A transcervical approach was employed in 19 patients, and a transoral approach was used in 8 patients. The 5-year rate of local RPM control was 92%. For the whole cohort, the 5- and 10-year DMFP were 72% and 62%, respectively; the 5- and 10-year DSS were 93% and 81%, respectively. Conclusions: DTC-associated RPMs manifest as recurrent disease in the majority of patients. Select patients with a small-volume and nonprogressive RPM may be suitable for observation, whereas surgery is likely warranted in large or progressing RPMs. In general, the presence of an RPM from DTC appears to be associated with aggressive disease. [ABSTRACT FROM AUTHOR]

Background: Inflammation and immune surveillance evasion are cancer hallmarks. Peripheral blood leukocytes (PBLs) represent both. The aim of the current study was to examine PBLs as predictors of outcomes in oral cavity squamous cell carcinoma (OSCC), and to find specific cutoffs with the goal of including PBLs as host factor in patients' preoperative risk assessment.Methods: Previously established head and neck squamous cell carcinoma (HNSCC) cutoffs were examined in an independent cohort of 1369 OSCC patients. Then optimal OSCC cutoffs were found and validated in the subset of patients with OSCC (n = 119) from the external HNSCC cohort. The PBLs analyzed were neutrophils, monocytes, and lymphocytes individually, the neutrophil-to-lymphocyte ratio (NLR), and a combined index using all PBLs called Systemic Inflammation Response Index (SIRI).Results: All parameters were significant predictors of survival using the previous cutoffs. However, OSCC cutoffs stratified survival outcomes better. Considering neutrophils ≤4.8 × 109 /L as reference, patients with 4.8-9.1 × 109 /L neutrophils had 1.536 times higher risk of death (95% CI, 1.295-1.822), and patients with ≥9.1 × 109 /L had 3.076 times higher risk (95% CI: 2.170-4.360). All PBLs maintained independent prognostic capacity in multivariable analysis. Neutrophils, NLR, and SIRI were significant predictors of survival when validating OSCC cutoffs in the external validation cohort.Conclusions: Pretreatment peripheral blood neutrophils, NLR, and SIRI are the most robust independent predictors of overall survival among all PBLs in OSCC. The authors report externally validated cutoffs that demonstrate the feasibility of including PBLs as host features in the preoperative prognostication of OSCC. [ABSTRACT FROM AUTHOR]

Objective: Polymorphous adenocarcinoma of salivary gland (PAC) is rare. Despite being described as a low risk histology, some patients develop regional and distant metastasis. More aggressive behavior has been attributed to a PAC subcategory called cribriform adenocarcinoma of minor salivary glands (CAMSG). We examined oncological outcomes of PAC.Patients and Methods: Fifty-seven patients with PAC were identified from an institutional database of 884 patients surgically treated for salivary gland malignancies from 1985 to 2015. Detailed histopathological analysis was performed. Survival outcomes were calculated using the Kaplan-Meier method. Factors predictive of recurrence were identified using the Cox proportional hazard method.Results: Fifty-four (95%) had tumors of minor salivary gland origin; the most frequent location was the oral cavity in 41 (76%), specifically the hard palate in 32 (55%). Forty-six patients (81%) were clinical T1-T2; 3 (5%) had a clinically positive neck. Thirty-two patients (56%) were classified as PAC and 14 (25%) as CAMSG. Forty-four patients (77%) had surgery alone; 13 (23%) had surgery and postoperative radiotherapy. The 5- and 10-year overall survival and disease-specific survival were 88% and 79% and 98% and 94%, respectively (median follow up 84 [1-159] months); 5- and 10-year recurrence-free survival were 93% and 88%, respectively. Univariate analysis showed male sex, III/IV stage, and CASMG variant had increased incidence of recurrence but were not statistically significant.Conclusion: PAC of the salivary glands is an indolent disease with good survival outcomes. Recurrence is uncommon and tends to occur late. Long-term follow-up is indicated in patients with this disease. [ABSTRACT FROM AUTHOR]

Objective: Previous population-based studies in salivary gland carcinomas have described a relationship between female sex and superior oncological outcome.Patients and Methods: Our institutional database of 884 surgically treated patients with salivary gland malignancies from 1985 to 2015 was analyzed for the impact of sex on oncological outcomes. Histologies were classified in three risk groups, low, intermediate and high. Survival outcomes were determined using the Kaplan-Meier method. Hazard ratios for male sex were determined using the Cox proportional hazards model.Results: Eight hundred sixty-seven patients were identified; median age was 59 years, and 51% had a minor salivary gland malignancy. Female patients were younger (58 versus 60 years; p = 0.040) and had a lower incidence of high-risk histologies (25% versus 40%, p < 0.001) and T3-T4 tumors compared to men (23% versus 31%, p < 0.001). With a median follow-up of 57 months, female patients had a superior 5-year disease-specific survival (DSS) (90% versus 79%; p < 0.001). The unadjusted hazard ratio showed male patients had a 2.15-fold increased risk of death (HR 2.15; 95% CI, 1.50-3.06, p < 0.001). After adjusting for Charlson comorbidity index, tobacco use, histological risk group, and overall pathological stage, males still had a statistically significant increased risk of death (HR 1.48; 95% CI 1.05-2.17; p = 0.047). Subgroup analysis showed DSS for females was significantly better in the high-risk histological group (5-year 68% versus 49%, p = 0.007).Conclusion: Our study shows that sex has an impact on cancer-specific survival and that female sex favors improved survival. [ABSTRACT FROM AUTHOR]

Insulinomas are rare endocrine malignancies of the pancreas that require surgical resection but can be difficult to localize preoperatively. We sought to review and improve the accuracy of preoperative localization techniques at our institution. We retrospectively reviewed all insulinomas that underwent resection at our institution between 1998 and 2016. Localization techniques include selective arterial calcium stimulation (CaStim), CT, MRI, angiography, and somatostatin receptor scintigraphy. Thirty-eight patients had pathologically proven insulinomas on surgical resection. Localization accuracies of CaStim, CT, and MRI were 89 per cent (31/35), 67 per cent (22/33), and 46 per cent (11/24), respectively. When compared with CT alone and CaStim alone, the combination of these two modalities resulted in 100 per cent preoperative localization (30/30), whereas the use of CaStim alone resulted in 80 per cent (4/5) localization and the use of CT alone resulted in 66 per cent (2/3) localization. Four of our patients had both negative CT and MRI. Among these patients, CaStim was 100 per cent localizing and the only positive modality for these patients. These data confirm that CaStim is accurate in preoperatively identifying single and multiple insulinomas; and when combined with CT, this accuracy is increased to 100 per cent. Based on these data, we propose that a dual imaging approach is a superior means of preoperative localization. [ABSTRACT FROM AUTHOR]

Background: Existing patient-reported outcome measures (PROMs) used to assess patients with head and neck cancer have methodologic and content deficiencies. Herein, the development of a PROM that meets a range of clinical and research needs across head and neck oncology is described.Methods: After development of the conceptual framework, which involved a literature review, semistructured patient interviews, and expert input, patients with head and neck cancer who were treated at Memorial Sloan Kettering Cancer Center were recruited by their surgeon. The FACE-Q Head and Neck Cancer Module was completed by patients in the clinic or was sent by mail. Rasch measurement theory analysis was used for item selection for final scale development and to examine reliability and validity. Scale scores for surgical defect and adjuvant therapy were compared with the cohort average to assess clinical applicability.Results: The sample consisted of 219 patients who completed the draft scales. Fourteen independently functioning scales were analyzed. Item fit was good for all 102 items, and all items had ordered thresholds. Scale reliability was acceptable (person separation index was >0.75 for all scales; Cronbach α values were >.87 for all scales; test-retest ranged from 0.86 to 0.96). The scales performed well in a clinically predictable way, demonstrating functional and psychosocial differences across disease sites and with adjuvant therapy.Conclusions: The scales forming the FACE-Q Head and Neck Cancer Module were found to be clinically relevant and scientifically sound. This new PROM now is validated and ready for use in research and clinical care. [ABSTRACT FROM AUTHOR]

Objectives: To present treatment results of oral squamous cell carcinoma (OSCC) at a tertiary cancer care center from 1985 to 2015.Materials and Methods: A total of 2082 patients were eligible for this study. Main outcomes measured were overall survival (OS) and disease specific survival (DSS). Prognostic variables were identified with bivariate analyses using Kaplan-Meier curves and log-rank testing for comparison. A p-value < 0.05 was considered statistically significant and significant factors were entered into multivariate analysis. Median age was 62 years (16-100), 56% were men, 66% reported a history of tobacco use and 71% of alcohol consumption. The most common subsite was tongue (51%). Seventy-three percent of patients had cT1-2 and 71% had clinically negative necks (cN0). Surgery alone was performed in 1348 patients (65%), adjuvant postoperative radiotherapy in 608 patients (29%) and postoperative chemoradiation in 126 patients (6%). Neck dissection was performed in 920 patients with cN0, and in 585 patients with a clinically involved neck. The median follow-up was 37.6 months (range 1-382).Results: The 5-year OS and DSS were 64.4% and 79.3%, respectively. Age, comorbidities, margin status, vascular invasion, perineural invasion, AJCC 8th edition pT, and pN were independent prognostic factors of OS (p < 0.05). History of alcohol consumption, margin status, vascular invasion, perineural invasion, pT, and pN were independent prognostic factors of DSS (p < 0.05).Conclusion: pN stage is the most powerful and consistent predictor of outcome in patients with OSCC treated with primary surgery and appropriate adjuvant therapy. [ABSTRACT FROM AUTHOR]

• Use of PET/CT for post-operative radiation planning is associated with increased detection of early recurrence. • Patients with intermediate risk clinicopathologic risk factors disproportionately benefit from post-operative PET/CT due to a higher likelihood of major treatment intensification. • Use of post-operative PET/CT is associated improved disease-free survival among patients with intermediate risk clinicopathologic risk factors. We evaluate the impact of post-operative 18-fluorodeoxyglucose positron emission tomography with computed tomography (PET/CT) for radiation planning on the detection of early recurrence (ER) and treatment outcomes in oral squamous cell carcinoma (OSCC). We retrospectively reviewed the records of patients treated with post-operative radiation between 2005 and 2019 for OSCC at our institution. Extracapsular extension and positive surgical margins were classified as high risk features; pT3-4, node positivity, lymphovascular invasion, perineural invasion, tumor thickness >5 mm, and close surgical margins were considered intermediate risk features. Patients with ER were identified. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances between baseline characteristics. 391 patients with OSCC were treated with post-operative radiation. 237 (60.6%) patients underwent post-operative PET/CT planning vs. 154 (39.4%) who were planned with CT only. Patients screened with post-operative PET/CT were more likely to be diagnosed with ER than those planned with CT only (16.5 vs. 3.3%, p < 0.0001). Among patients with ER, those with intermediate features were more likely than those high risk features to undergo major treatment intensification, including re-operation, the addition of chemotherapy, or intensification of radiation by ≥ 10 Gy (91% vs. 9%, p < 0.0001). Post-operative PET/CT was associated with improved disease-free and overall survival for patients with intermediate risk features (IPTW log-rank p = 0.026 and p = 0.047, respectively) but not high risk features (IPTW log-rank p = 0.44 and p = 0.96). Use of post-operative PET/CT is associated with increased detection of early recurrence. Among patients with intermediate risk features, this may translate to improved disease-free survival. [ABSTRACT FROM AUTHOR]

Background: Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC.Methods: Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis.Results: Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03).Conclusions: Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018;124:2948-55. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives: Neck failure in patients with oral squamous cell carcinoma (OSCC) carries a poor outcome, yet the management of patients who initially present with clinically node-negative (cN0) neck is not clearly defined.Patients and Methods: Retrospective review of patients with cN0 OSCC treated at Memorial Sloan Kettering Cancer Center from 1985 to 2012, focusing on rate, pattern and predictors of neck failure, salvage treatment, and survival outcomes.Results: Of 1,302 patients, 806 (62%) underwent elective neck dissection (END) and 496 (38%) had observation. 190 patients (15%) developed neck recurrence. Median follow-up was 58.5 months (range 1-343); 5-year neck recurrence-free survival (NRFS) was 85% and 80% for the END and observation group respectively (p = .06). Patients with neck failure had poorer outcomes than patients without neck failure (5-year overall survival, 37% vs. 74% [p < .001]; disease-specific survival [DSS], 41% vs. 91% [p < .001]). Independent predictors of neck failure were smoking, primary tumor subsite (hard palate and upper gum), and extranodal extension. 87% of patients underwent salvage treatment (END: 81.1%; observation: 94%). Salvage surgery with adjuvant (chemo) radiation had better DSS than surgery alone or nonsurgical salvage.Conclusions: In our cohort of patients with initially cN0 OSCC triaged to END vs. observation using clinical parameters, 15% developed neck failure. Salvage treatment was feasible in most cases but survival was poorer compared to patients without neck failure. Surgery followed by adjuvant (chemo) radiation resulted in the best outcome. [ABSTRACT FROM AUTHOR]

Objectives: To determine the need for a separate staging system for gingivobuccal complex squamous cell cancers (GBCSCC) based on 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) data from one institution.Patients and Methods: An Institutional Review Board (IRB)-approved retrospective analysis was performed on an oral cavity cancer patient database. Patients from 1985 to 2012 with primary surgical treatment for biopsy-proven squamous cell cancer (SCC) from either the oral tongue (TSCC Group) or gingivobuccal complex (GBCSCC Group), were selected as two separate subgroups. The clinicopathologic data were used to stage the patients based on the American Joint Committee on Cancer 7th edition. Survival outcomes including 5-year OS, RFS, and DSS were calculated and analyzed. A multivariate analysis was performed to identify if subsite was an independent predictor for the survival outcomes, adjusting for other variables. A p-value of less than .05 was considered statistically significant.Results: 936 patients with TSCC and 486 patients with GBCSCC were considered eligible for the analysis. Patients with GBCSCC were more likely to be older (p < .001) and presented with more advanced disease (p < .001) compared to patients with TSCC. Unadjusted hazard ratio (HR) suggested GBCSCC had poor OS compared to TSCC. However, after adjusting for other variables, the adjusted HR was not significant (p = .593). There was no difference in 5-year DSS or RFS in either of the study groups.Conclusion: With similar survival outcomes by stage, there is no justification for using a different staging system for GBCSCC. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to report our incidence of clinically evident neck recurrence, salvage neck management and subsequent outcomes in patients with papillary thyroid cancer. This is important to know so that patients with thyroid cancer can be properly counselled about the implications of recurrent disease and subsequent outcome. Methods An institutional database of 3664 patients with thyroid cancer operated between 1986 and 2010 was reviewed. Patients with nonpapillary histology and gross residual disease and those with distant metastases at presentation or distant metastases prior to nodal recurrence were excluded from the study. Of these, 99 (3.0%) patients developed clinically evident nodal recurrence. Details of recurrence and subsequent therapy were recorded for each patient. Subsequent disease-specific survival ( sDSS), distant recurrence-free survival ( sDRFS) and nodal recurrence-free survival ( sNRFS) were determined from the date of first nodal recurrence using the Kaplan-Meier method. Results Of the 99 patients, 59% were female and 41% male. The median age was 41 years (range 5-91). The majority of patients had pT3/4 primary tumours (63%) and were pN+ (78%) at initial presentation. The median time to clinically evident nodal recurrence was 28 months (range: 3-264). Nodal recurrence occurred in the central neck in 15 (15%) patients, lateral neck in 74 (75%) patients and both in 10 (10%) patients. After salvage treatment, the 5-year sDSS was 97.4% from time of nodal recurrence. The 5-year sDRFS and sNRFS were 89.2% and 93.7%, respectively. Conclusion In our series, isolated clinically evident nodal recurrence occurred in 3.0% of patients. Such patients are successfully salvaged with surgery and adjuvant therapy with sDSS of 97.4% at 5 years. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on the quasi-experimental analysis of radioactive iodine, which references the study "Use of radioactive iodine for thyroid cancer," by M. R. Haymart and colleagues and the guidelines published by the American Thyroid Association (ATA) in 2009.

Objectives: To report the complications occurring following TORS and to identify the factors predictive of complications.Methods: Following IRB approval a retrospective analysis of all TORS operations at our institution was performed. Postoperative complications within 45days were collected and graded with the Clavien-Dindo system. Complications were categorized into groups: all complications, not related to TORS and TORS related. Unadjusted odds ratios were calculated to test association between patients with and without a complication.Results: 122 TORS operations were carried out between June 2010 and August 2015. 77% were male, with a median age of 57. There were 92 primary tumor resections, 10second head and neck primary resections, 13 salvage procedures and 7 other indications. Surgical resection involved 1, 2 or >3 sub-sites in 36%, 28% and 36% patients, respectively. Overall, there were 107 complications (66 TORS related, 41 non-TORS related) that occurred in 57 patients (47%). A major complication occurred in 23 patients (18%). 19 patients had a TORS related major complication and 6 patients experienced a non-TORS related major complication. There was a temporal trend in TORS related major complication rate decreasing from 33% in 2010 to 10% in 2015. Statistical analysis showed that the odds of having any complication were 3 times greater in patients over 60years old (p=0.017), and 2.5 times greater when there were more than 2 subsites resected (p=0.022).Conclusions: Age over 60years and a larger extent of resection were the significant factors predictive of major complications. [ABSTRACT FROM AUTHOR]

Background: Radiation exposure, especially in childhood, is known to increase the risk for the development of thyroid cancer. However, the prognosis of patients with thyroid cancer with a history of radiation treatment exposure remains unclear. Methods: One hundred and sixteen patients with a previous history of radiotherapy in the head and neck region were identified from an institutional database of 3664 patients with differentiated thyroid cancer treated between 1986 and 2010. Using the Kaplan-Meier method, disease-specific survival and recurrence-free survival were compared between patients with (RT; n = 116) and without (No RT; n = 3509) a prior history of radiation exposure. Results: The median ages of the RT and No RT cohorts were 52 and 47 years. The median follow-up for both groups was 54 months. Patients who had a prior history of radiation treatment exposure were more likely to be male (38.8% vs. 26.9%; p = 0.005) and older than 45 years of age (67.2% vs. 53.9%; p = 0.005). Other patient, tumor, and treatment characteristics were similar between the groups. There was no difference in the five-year disease-specific survival of the RT and No RT patients (97.4% vs. 98.7%; p = 0.798). The five-year recurrence-free survival was also similar between the RT and No RT patients (97.8% vs. 94.9%; p = 0.371). Conclusion: The findings suggest that differentiated thyroid cancer patients with a history of prior radiation treatment exposure have similar outcomes to those with no history of head and neck radiation exposure. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with increased adipose tissue in the tongue. Chronic white adipose tissue (WAT) inflammation commonly occurs in the obese. We investigated whether WAT inflammation in the tongue impacts survival in patients with squamous cell carcinoma (SCC) of the oral tongue.Methods: In a retrospective cohort study, patients with T1 and T2 SCC of the oral tongue who underwent curative-intent resection were included. Tongue WAT inflammation was defined by the presence of dead or dying adipocytes surrounded by macrophages forming crown-like structures. The primary and secondary endpoints were disease-specific survival (DSS) and overall survival (OS), respectively. Subgroup analyses were carried out in patients without lymph node involvement for whom adjuvant therapies were not indicated.Results: Archived tissue was available from 125 patients. The median follow-up was 55 months (range, 3-156 months). Overall, 49 of 125 patients (39%) had tongue WAT inflammation, which was associated with higher body mass index, increased tumor thickness, and vascular invasion (P < .05). The 3-year DSS rate for patients with tongue WAT inflammation was 59% (95% confidence interval [CI], 46%-76%) versus 82% (95% CI, 73%-92%) for those without inflammation. For patients without lymph node involvement for whom adjuvant therapy was not indicated (N = 70), tongue WAT inflammation was associated with shortened DSS and OS (P < .05). When adjusted for body mass index and potential prognostic covariates, the hazard ratio for DSS and OS was 5.40 (95% CI, 1.20-24.26) and 2.97 (95% CI, 1.02-8.65), respectively.Conclusions: Tongue WAT inflammation is associated with worse DSS and OS in patients who have early stage SCC of the oral tongue. Cancer 2016;122:3794-3802. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: There has been increasing interest in the primary surgical treatment of patients with early T classification (T1-T2) oropharyngeal squamous cell carcinoma (OPSCC), with the stated goal of de-escalating or avoiding adjuvant treatment. Herein, the authors sought to determine the degree to which this interest has translated into changes in practice patterns, and the rates of adverse postoperative pathologic features.Methods: Patients with T1 to T2 OPSCC in the National Cancer Data Base who were treated from 2004 through 2013 were categorized as receiving primary surgical or primary radiation-based treatment. Trends in treatment selection and factors related to the selection of primary surgery were examined. The rates of adverse pathologic features including positive surgical margins, extracapsular spread (ECS), and advanced T and N classifications after surgery were analyzed.Results: Of 8768 patients with T1 to T2 OPSCC, 68% underwent primary surgical treatment, increasing from 56% in 2004 to 82% in 2013 (P<.0001). The highest versus lowest volume hospitals treated 78% versus 59% of patients with primary surgery (odds ratio, 2.23; 95% confidence interval, 1.55-3.22 [P<.0001]). Higher lymph node classification was found to be predictive of lower rates of primary surgery, but the majority of patients with clinical N2/N3 disease underwent primary surgery. Among patients treated with surgery, positive surgical margins were present in 24% and ECS in 25% of patients. The rate of positive surgical margins decreased over time (P<.0001) and was observed less often at high-volume centers (P<.0001). Among candidates for single-modality therapy (those with clinical T1-T2/N0-N1 disease), 33% had positive surgical margins and/or ECS and 47% had at least 1 adverse feature (T3-T4 disease, N2-N3 disease, positive surgical margins, and/or ECS).Conclusions: Primary surgical treatment among patients with early T classification OPSCC has become more widespread. Cancer 2016;122:1523-32. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Following total thyroidectomy ( TT) for papillary thyroid cancer ( PTC), pathological assessment can occasionally reveal incidental perithyroidal lymph nodes ( LNs) with occult metastases. These cN0pN1a patients often receive radioactive iodine ( RAI) therapy for this indication alone . The aim of this study was to determine the central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. Methods An institutional database of 3664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010 was reviewed. A total of 232 pT1-3 patients managed with TT and no neck dissection were subsequently found to have incidental level 6 LNs on pathology. Patients with other indications for RAI, such as extrathyroidal extension and close or positive margins, were excluded. One hundred and four patients remained for analysis. Kaplan-Meier method was used to determine central neck LN recurrence-free survival ( RFS). Results The median age of the cohort was 40 years (range 17-83). The median follow-up was 53 months (range 1-211). The median number of positive LNs removed and maximum LN diameter were 1 (range 1-8) and 5 mm (range 1-16 mm), respectively. A total of 67 (64%) patients had adjuvant RAI and 37 (36%) did not. Patients with vascular invasion ( P = 0·01), LNs >2 mm ( P = 0·07) and >2 positive nodes ( P = 0·06) were more likely to be selected for adjuvant RAI therapy. Patients without RAI therapy had similar 5-year central neck LN RFS compared to those treated with RAI: 96·2% vs 94·6%, respectively ( P = 0·92). Conclusion There is no difference in the 5-year central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. [ABSTRACT FROM AUTHOR]

Background: The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost-effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories.Methods: Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services.Results: The median age was 44 years (range, 7-83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively.Conclusions: The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured. [ABSTRACT FROM AUTHOR]

Background: In most staging systems, 45 years of age is used to differentiate low risk thyroid cancer from high risk thyroid cancer. However, recent studies have questioned both the precise 45 year age point and the concept of using a binary cut off as accurate predictors of disease specific mortality. Methods: A cohort of 3664 thyroid cancer patients that received surgery and adjuvant treatment at Memorial Sloan Kettering Cancer Center (MSKCC) from the years 1985 to 2010 were analyzed to determine the significance of age at diagnosis as a categorical variable at a variety of age cutoffs (5 year intervals between 30 and 70 years of age). The unadjusted and adjusted hazard ratio for the association between disease-specific survival and age was determined using a Cox proportional hazards model adjusted for other predictive variables sex, histology, and pathological T, N, and M status. Furthermore, predictive nomograms of disease-specific mortality were created and validated on an external dataset of 4551 patients to evaluate the impact of age at diagnosis as both a categorical and continuous variable. Results: In the MSKCC cohort, with a median follow-up time of 54 months (range 1-332), there were 59 deaths from thyroid cancer with a 10 year disease-specific survival of 96%. Adjusted hazard ratios for all age cutoffs from age 30 to age 70 years were significant. There was no specific cutoff age which risk stratifies patients with differentiated thyroid cancer (DTC). Categorizing age into five strata (<40, 40-49, 50-59, 60-69 and >70 years) showed a 37-fold increase in hazard ratio from age <40 years to age >70 years. A predictive nomogram using age as a continuous variable with other predictive variables had a high concordance index of 96%. Validation on the external cohort had a concordance index of 73%. Conclusions: Mortality from DTC increases progressively with advancing age. There is no specific cutoff age which risk stratifies patients with DTC. A predictive nomogram using age as a continuous variable may be a more appropriate tool for stratifying patients with DTC and for predicting outcome. [ABSTRACT FROM AUTHOR]

Background: In contrast to other head and neck cancers, the impact of histological thyroid specimen margin status in differentiated thyroid cancer (DTC) is not well understood. The aim of this study was to investigate the prognostic value of margin status on local recurrence in DTC. Method: The records of 3664 consecutive patients treated surgically for DTC between 1986 and 2010 were identified from an institutional database. Patients with less than total thyroidectomy, unresectable or gross residual disease, or M1 disease at presentation and those with unknown pathological margin status were excluded from analysis. In total, 2616 patients were included in the study; 2348 patients (90%) had negative margins and 268 patients (10%) had positive margins. Microscopic positive margin status was defined as tumor present at the specimen's edge on pathological analysis. Patient, tumor, and treatment characteristics were compared by Pearson's chi-squared test. Local recurrence free survival (LRFS) was calculated for each group using the Kaplan Meier method. Results: The median age of the cohort was 48 years (range 7-91 years) and the median follow-up was 50 months (range 1-330 months). Age, sex, and histology types were similar between groups. As expected, patients who had positive margins were more likely to have larger tumors ( p<0.001), extrathyroidal extension (ETE) ( p<0.001), multicentric disease ( p<0.001), or nodal disease ( p<0.001) and were more likely to receive adjuvant radioactive iodine therapy ( p<0.001) as well as external beam radiotherapy ( p<0.001). The LRFS at 5 years for patients with positive margins status was slightly poorer compared with patients with negative margins (98.9% vs. 99.5%, p=0.018). Twelve patients developed local recurrence-8/2348 (0.34%) patients with negative margins and 4/263 (1.52%) patients with positive margins. Univariate predictors of LRFS were sex ( p=0.006), gross ETE (<0.001), and positive margins ( p=0.018). However, when controlling for presence of gross ETE on multivariate analysis, microscopic positive margin status was not an independent predictor of LRFS ( p=0.193). Conclusion: Patients with resectable, M0 disease that undergo total thyroidectomy have an excellent five year LRFS of 99.4%. Microscopic positive margin status was not a significant predictor for local failure after adjusting for ETE or pathological tumor (pT) stage. [ABSTRACT FROM AUTHOR]

BACKGROUND Survival rates are commonly used to measure success in treating cancer, but can be misleading. Modern diagnostic practices can lead to the appearance of improving cancer survival, as tumors are diagnosed earlier (lead-time bias) or as an increasing proportion are slow-growing (length bias), whereas the actual burden of cancer deaths is unchanged. Increasingly, more subclinical thyroid cancers are being diagnosed. The objective of the current study was to determine whether thyroid cancer survival rates have been affected by this phenomenon. METHODS The authors analyzed survival data from patients with thyroid cancer who were treated at Memorial Sloan Kettering Cancer Center (MSKCC) from 1950 to 2005, and United States population-based incidence, prevalence, and survival data from 1973 to 2009 in the Surveillance, Epidemiology, and End Results data set. RESULTS US thyroid cancer incidence has increased 3-fold from 1975 to 2009. Over time, the proportion of thyroid cancers that are subcentimeter in size has increased from 23% (1983) to 36% (2009). At MSKCC, this percentage rose from 20% (1950) to 35% (2005). The incidence rates of large tumors (>6 cm) and distant metastasis have not changed. In the United States, 10-year relative survival improved from 95.4% to 98.6% (1983-1999). At MSKCC, 10-year disease-specific survival improved from 91.1% to 96.1% (1950-2005). However, when stratified by tumor size and stage, no changes in survival outcomes were observed. US thyroid cancer mortality rates have remained stable (1975-2009). CONCLUSIONS Modern medical practices increasingly uncover small, asymptomatic thyroid cancers. Survival rates appear improved, but this finding is spurious, attributable instead to shifts in the characteristics of disease being diagnosed. Relying on survival rates to measure success in treating thyroid cancer may reinforce inappropriately aggressive management. Treatment decisions in thyroid cancer should be made based on mortality, not survival data. Cancer 2015;121:1793-1799. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Vascular invasion (VI) is an important predictor of distant metastasis and possible radioactive iodine (RAI) benefit in follicular, Hürthle cell, and poorly differentiated thyroid carcinomas, but its role in well-differentiated papillary thyroid cancer (WDTC) remains unclear. Methods: Archived pathological material of all differentiated thyroid carcinoma patients undergoing primary surgical treatment at Memorial Sloan-Kettering Cancer Center between 1986 and 2003 was reviewed by two dedicated thyroid pathologists. Only WDTCs were included in the present study. Standard statistical methods were used to assess the relationship between VI and outcomes of interest, including 10-year disease-specific survival (DSS), regional recurrence-free survival (RRFS), and distant recurrence-free survival (DRFS). Results: VI was present in 47 of 698 WDTC (6.7%). VI was significantly associated with tumor size >4.0 cm, extrathyroidal extension, distant metastasis, and RAI treatment. On univariate analysis, VI was predictive of decreased 10-year DRFS, but not DSS or RRFS. On multivariate analysis, VI was not an independent predictor of DRFS. Univariate survival analysis of 422 RAI-naïve WDTC showed that both size >4 cm and VI were predictors of outcome, but only size remained independently predictive on multivariate analysis. Conclusion: The presence of VI is not an independent predictor of outcome in WDTC. [ABSTRACT FROM AUTHOR]