A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer.

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.

Distant metastasis of salivary gland cancer: Incidence, management, and outcomes.

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.

Minor salivary gland tumors of the head and neck-Memorial Sloan Kettering experience: Incidence and outcomes by site and histological type.

BACKGROUND: Minor salivary gland carcinomas of the head and neck are rare cancers with variable clinical behavior. This study explored the incidence, pathology, clinical behavior, and factors predictive of outcomes in a large cohort of patients treated at Memorial Sloan Kettering Cancer Center over a 30-year period (1985-2015). METHODS: Clinical, pathological, treatment, and outcome data were collected. Unadjusted and adjusted hazard ratios for each variable were calculated with univariate and multivariable Cox regression for survival and recurrence outcomes. RESULTS: Four hundred fifty patients were included: 55% were female, 56% were younger than 60 years, and the median follow-up was 74 months (range, 1-364 months). The most common site was the oral cavity with 305 tumors (68%), which was followed by the oropharynx with 96 (21%), the sinonasal cavity with 38 (8%), the trachea with 7 (2%), and the larynx with 4 (1%). The most common histological types were mucoepidermoid carcinoma (180 tumors [40%]), adenoid cystic carcinoma (141 tumors [31%]), and polymorphous low-grade adenocarcinoma (54 tumors [12%]). The 5-year predicted overall survival rate was 86%, and the disease-specific survival rate was 94% at 5 years. Pathology and tumor stage were significant variables on multivariate analysis for overall survival, disease-specific survival, recurrence-free survival, local recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival. CONCLUSIONS: American Joint Committee on Cancer stage and pathology were the most predictive variables across all outcomes. Tumor site, postoperative radiotherapy, and margin status were not statistically significant variables after tumor stage and pathology were controlled for in most outcomes.

Intraoperative and postanesthesia care unit fluid administration as risk factors for postoperative complications in patients with head and neck cancer undergoing free tissue transfer.

BACKGROUND: This study aims to evaluate the impact of perioperative fluid administration, defined as fluid delivered intraoperatively and in the postanesthesia care unit, on postoperative outcomes. METHODS: Medical records of 102 patients with oral cavity squamous cell carcinoma undergoing free flap reconstruction between January 2011 and December 2015 were reviewed. The primary endpoint was development of a postoperative complication according to the Clavien-Dindo classification. Perioperative factors recorded were Washington University Head and Neck Comorbidity Index, operating time, vasopressor use, blood loss, intraoperative fluid, and perioperative fluid. RESULTS: Greater perioperative fluid administration was independently associated with surgical complications, flap complications, overall incidence of any complication, and increased length of stay. Greater intraoperative fluid administration was independently associated with higher rates of surgical complications. Intraoperative delivery of vasopressors was not associated with flap or surgical complications. CONCLUSION: Receiving less perioperative fluid was associated with fewer complications and decreased length of stay.

Molecular phenotyping and image-guided surgical treatment of melanoma using spectrally distinct ultrasmall core-shell silica nanoparticles.

Accurate detection and quantification of metastases in regional lymph nodes remain a vital prognostic predictor for cancer staging and clinical outcomes. As intratumoral heterogeneity poses a major hurdle to effective treatment planning, more reliable image-guided, cancer-targeted optical multiplexing tools are critically needed in the operative suite. For sentinel lymph node mapping indications, accurately interrogating distinct molecular signatures on cancer cells in vivo with differential levels of sensitivity and specificity remains largely unexplored. To address these challenges and demonstrate sensitivity to detecting micrometastases, we developed batches of spectrally distinct 6-nm near-infrared fluorescent core-shell silica nanoparticles, each batch surface-functionalized with different melanoma targeting ligands. Along with PET imaging, particles accurately detected and molecularly phenotyped cancerous nodes in a spontaneous melanoma miniswine model using image-guided multiplexing tools. Information afforded from these tools offers the potential to not only improve the accuracy of targeted disease removal and patient safety, but to transform surgical decision-making for oncological patients.

Complications following transoral robotic surgery (TORS): A detailed institutional review of complications.

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.

Concomitância de carcinoma papilífero e tireoidite de hashimoto em pacientes submetidos a tireoidectomia total: Análise da casuística e revisão da literatura / Coexistence of papillary thyroid carcinoma and hashimoto?s thyroiditis in patients submitted to total thyroidectomy: Retrospective case series and literature review

Introdução: A Tireoidite de Hashimoto (TH) é a causa mais comumde hipotireoidismo e é caracterizada pela insuficiência tireoidianaprogressiva de causa autoimune. O carcinoma papilífero detireoide (CPT) é a forma mais prevalente de câncer da tireoidecorrespondendo a 70 - 80% de todos os casos. Estudos atuaisdemonstram coexistência entre 11 e 38% entre TH e CPT e queas doenças compartilham muitas características morfológicase moleculares, mas a importância clínica desta correlaçãopermanece indefinida. Objetivo: Avaliar a concomitância deTH em doenças benignas e malignas em tireoidectomias totais.Método: No presente estudo comparamos a concomitância deTH em doenças benignas e malignas no anatomopatológico de100 tireoidectomias consecutivas realizadas entre os meses dejunho a setembro de 2009, por um mesmo cirurgião. Resultados:A presença de TH em casos malignos foi de 47,7% e em doençasbenignas de 26,7% (p<0,05). Conclusão: A coexistência de THe CPT é maior do que em doenças benignas, o que dá suporte àteoria de que a TH seja um fator de risco para o desenvolvimentodo CPT. Nódulos em pacientes com TH devem ser avaliadosprecocemente e seguidos com cautela.