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BACKGROUND This study aimed to assess whether surgical case volume for lateral neck dissection has an impact on the survival of patients who have well-differentiated thyroid cancer (WDTC) with lateral cervical node metastases. The authors used a population-based cohort study design. METHODS The study cohort consisted of WDTC patients in Ontario Canada who underwent thyroidectomy and lateral neck dissection. These patients were identified using both hospital- and surgeon-level administrative data between 1993 and 2017 (n = 1832). Surgeon and hospital volumes were calculated based on the number of cases managed in the year before the procedure by the physician and at the institution managing each case, respectively, and divided into tertiles. Multilevel Cox regression models were used to estimate the effect of volume on disease-free survival (DFS). RESULTS A crude model without patient or treatment characteristics demonstrated that DFS was associated with both higher surgeon volume tertiles (p < 0.01) and higher hospital volume tertiles (p < 0.01). After control for clustering, patient/treatment covariates, and hospital volume, the lowest surgeon volume tertile (range, 0-20/year; mean, 6.5/year) remained an independent statistically significant negative predictor of DFS (hazard ratio, 1.71; 95 % confidence interval, 1.22-2.4; p < 0.01). CONCLUSION Surgeon lateral neck dissection case volume is a predictor of better DFS for thyroid cancer patients, with the lowest surgeon volume tertile (

Several technologies have been implemented in orthopedic surgery to improve surgical outcomes, usually focusing on more accurate execution of a surgical plan, but the development of the plan itself is also of great importance. The purpose of this study is to examine whether the use of preoperative computer planning platforms can improve the surgical plan? Eight surgeons created a preoperative surgical plan to resect a distal femur parosteal osteosarcoma in two settings: (1) Using a 2-D and 3-D CT scan only (current standard); and (2) using a computer-assisted planning platform. The plans were thereafter virtually executed using a novel surgical navigation system and a Sawbones model. This simulated model was derived from, and identical to, an actual patient scenario. The outcomes of interest were the number of positive margin cuts, and the volume of the resected specimen. Using the surgical plan developed with computer assistance, there were 4 positive margin cuts made by 2 surgeons. In comparison, using standard planning, there were 14 positive margin cuts made by all 8 surgeons (p = 0.02). The resection volume was larger in the computer-assisted plans (96 ± 10 mm3) than in the standard plans (88 ± 7 mm3) (p = 0.055). Computer-assisted planning significantly decreased the risk of a positive margin resection in this Sawbones tumor model used to simulate resection of a primary bone sarcoma. This proof of concept study highlights the importance of advanced surgical planning and sets the ground for developing beneficial surgical planning systems.

Background Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. Methods Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. Results Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p Conclusion This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.

Gene-expression classifiers (GEC) and genetic mutation panels (GMP) have been shown to improve preoperative diagnostic evaluations of indeterminate thyroid nodules. Despite the improvement, uncertainty regarding the proper management exists. Patient preferences may better inform the management of these indeterminate thyroid nodules. Hypothetical scenarios were administered to two groups of patients: those with previous FNA-confirmed indeterminate thyroid nodules (Group A, n = 50) and those presenting to a general otolaryngology clinic for other reasons (Group B, n = 50). We evaluated patient preferences for surgery, observation and the use of molecular tests while varying the risk of malignancy, cost and diagnostic properties of the tests. The mean threshold for choosing surgery over observation was a 38.6% risk of malignancy on FNA. When offered either GEC, GMP or both (with their inherent imperfect diagnostic properties) in addition to the indeterminate FNA, 85.0% of respondents picked at least one of the molecular tests over either observation or surgery if the test(s) were free of charge. However, only 51.7% of respondents chose at least one of the tests when asked to pay the current cost of the test(s) (p

Background Plate-related complications following head and neck cancer ablation and reconstruction remains a challenging problem often requiring further management and reconstructive surgeries. We aim to identify an association between surgical site infections (SSI) and plate exposure. Methods A retrospective study between 1997 and 2014 was performed to study the association between postoperative SSI and plate exposures. Eligible patients included those with a history of oral squamous cell carcinoma who underwent surgical resection, neck dissection, and free tissue reconstruction. Demographic and treatment related information was collected. SSI were classified based on CDC definition and previously published literature. Univariable analysis on demographic factors, smoking history, diabetes, radiation, surgical and hardware related factors; while multivariable analysis on SSI, plate height, segmental mandibulectomy defects and radiation were conducted such as using cox proportional hazard models. Results Three hundred sixty-five patients were identified and included in our study. The mean age of the study group was 59.2 (+/−13.8), with a predominance of male patients (61.9%). 10.7% of our patient cohort had diabetes, and another 63.8% had post-operative radiation therapy. Patients with SSI were more likely to have plate exposure (25 vs. 6.4%, p

Multidisciplinary cancer conferences (MCCs) facilitate the discussion of appropriate diagnostic and treatment options for an individual cancer patient. In 2007, a study conducted in Ontario found that 52 % of hospitals were able to provide access to MCCs. In 2006, Cancer Care Ontario published minimum standards for MCCs. A framework for measurement was developed to monitor MCCs at the hospital, regional, and provincial level. The objective of this study was to review the results from initial efforts to improve quality and access through a population-based intervention.Data collection was completed prospectively between October to December in 2009, 2010, and 2011. A criterion satisfaction score (CSS) was developed on the basis of indicators including MCC frequency, type of patient case review, the presence of a chair and coordinator, and the attendance of appropriate medical staff members. For each hospital and region, the overall number of MCCs, patients discussed, and CSSs was calculated.Data were available from 13 of 14 regions in 2009 and all 14 regions in 2010 and 2011. The number of MCCs increased from 660 in 2009 to 798 in 2011 (p = 0.06). The number of patients discussed at MCCs increased from 4,695 in 2009 to 5,702 in 2011 (p = 0.22). The CSS scores across the regions improved significantly across 2009-2011 (p0.001).A population-based intervention has been associated with an improvement in access and quality of MCCs.

Unlike papillary thyroid carcinoma, medullary thyroid carcinoma is insensitive to adjuvant treatment with radioactive iodine. The clinical management of patients with advanced or metastatic disease remains challenging since no effective systemic adjuvant therapy is available. We aimed to identify markers of aggressive disease and novel drugable protein targets that would provide systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma. We therefore examined morphologic features of aggressive behavior and the expression of 41 proteins involved in apoptosis, cell cycle, angiogenesis, inflammation, cell adhesion, tumor-specific markers, and WNT, SHH, and AKT pathways using tissue microarray from 23 patients with medullary thyroid carcinoma. Protein expression was determined using computerized image analysis software. Statistical analysis was carried out to correlate clinical data with the average score for each marker. Angioinvasion proved to be the most reliable predictor of disease recurrence and death. The rate of angioinvasion was 43 %. All angioinvasive medullary thyroid carcinomas had locoregional and/or distant metastasis; 60 % of angioinvasive medullary thyroid carcinomas developed distant metastasis. We identified expression of several potentially important protein targets such as COX-1/2, Bcl-2a, Gst-π, Gli-1, Gli-2, Gli-3, and Bmi-1 that may be therapeutically targeted in medullary thyroid carcinoma. More importantly, the immunohistochemical profile of SSTRs in medullary thyroid carcinoma may also have clinical relevance for the administration of peptide receptor radionuclide treatment. Successful outcome of clinical trials directed against these novel targets would provide much needed systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma, and our data suggest the possibility of stratifying patients who are likely to require adjuvant therapy before their burden of disease precludes successful therapeutic effect.

The causative role of human papillomavirus (HPV) in a subset of squamous cell carcinomas of the oropharynx (OSCC) is now well established with HPV-16 being detected in approximately 92 % of HPV-positive OSCC in North America. Recently HPV has also been found in some non-squamous oropharyngeal carcinomas including adenosquamous carcinomas, neuroendocrine carcinomas, and undifferentiated “lymphoepithelioma-like” carcinomas. Herein, we report a HPV-16 positive adenocarcinoma NOS arising in the base of the tongue of a non-smoker, 64 year-old male. To our knowledge, this is the first time this association has been clearly documented. The adenocarcinoma was diffusely positive for p16 and HPV-16 was demonstrated by in situ hybridization and linear array analysis. Q-PCR demonstrated a viral load of 4 copies per cancer cell, whereas qRT-PCR for E6/E7 transcript levels were 30 copies per 1,000 human ribosomal protein large P0 (RPLP0) reference gene. The presence of HPV in non-squamous oropharyngeal carcinomas raises the possibility that HPV is also involved in the carcinogenesis of some uncommon carcinomas of the region.

Hyalinizing clear cell carcinoma (HCCC) is a rare, low-grade salivary gland tumor with clear cells and hyalinized stroma. Prognosis of HCCC is excellent with few cases metastasizing to the lymph nodes and lung. We present a case of a 61-year-old male with recurrent HCCC on the base of tongue. Histologic examination revealed sheets of clear and eosinophilic cells with a background of a myxoid-like matrix. In addition, large, bizarre malignant cells, focal necrosis, and atypical mitotic figures were identified. By immunohistochemistry, the clear cells were positive for CK18, EMA and vimentin, focally positive for CK7 and CD10, but negative for p63, HMWK, SMA and calponin. A metastatic renal cell carcinoma was considered a possibility but the tumor was called “poorly-differentiated carcinoma, NOS”. The patient underwent primary radiotherapy. A recurrence was identified at 10 months follow-up. A biopsy of the recurrent tumor showed clear cell differentiation and a predominant cribriform pattern with focal cords of eosinophilic cells invading the stroma. In contrast to the original tumor, no mitotic figures, atypia or necrosis were identified. The combination of lower grade and different architectural patterns appeared markedly different than the previous biopsy and the immunohistochemical pattern was also different. The recurrent tumor showed diffuse positivity for p63 and HMWK. It was negative for CD10, vimentin, SMA and calponin. Fluorescence in situ hybridization (FISH) analysis was positive for rearrangement of the EWSR1 gene in both samples, confirming that this represented a recurrence of the same tumor. It also confirmed that the initial tumor was a HCCC with high-grade transformation.

The objective of this study is to report the long-term outcomes of salvage surgery following local and/or regional failure of tonsillar carcinoma treated with standard fractionation radiotherapy. All cases of carcinoma of the tonsil treated by radical radiotherapy at the Princess Margaret Hospital between January 1970 and December 1990 were reviewed retrospectively. Patients who underwent salvage surgery for local and/or regional recurrent squamous cell carcinoma of the tonsil following radiation therapy were included for analysis. 239 out of 640 patients with tonsillar carcinoma recurred post radiotherapy. 175 patients were deemed candidates for surgical salvage. At the time of the last follow-up, only 13 patients were alive and 162 patients had died. The majority of patients (n = 96, 59%) died with disease. The median time to death was approximately 1.3 years following salvage surgery. The 5-year overall survival rate was 23%. The 5-year cause-specific survival was 40%. The probability of death due to disease was higher than the probability of death due to other causes. Both N-classification and T-classification were found to be significant predictors of time to death. In conclusion, in spite of the fact that the patients in this study had been treated prior to the widespread introduction of altered fractionation and concurrent chemoradiation for advanced tonsil carcinoma, it demonstrates the poor prognosis of recurrent disease. Despite the poor prognosis, 20% of patients will be alive at 5 years and therefore salvage surgery should be considered when possible.

Background Increasing evidence shows that Human Papillomavirus (HPV) is preferentially associated with some head and neck squamous cell carcinomas (HNSCCs), with variable infection rates reported. Methods We assessed HPV involvement in HNSCC using the Roche Linear Array HPV Genotyping Test, which can detect 37 different HPV types. We examined the prevalence of HPV infection in 92 HNSCCs (oropharynx, oral cavity, and other HNSCC sites). Results HPV was frequently detected in oropharyngeal cancers (OPCs) (16/22, 73%), but was uncommon in oral cavity cancers (2/53, 4%), and in other HNSCC subsites (1/17, 6%). HPV positive tumors were associated with patients that were 40-60 years old (p = 0.02), and node positive (p = < 0.0001). HPV 16 was the most prevalent type, but other types detected included 6, 18, 33, 35, 45, and 52/58. Conclusion Our results show that in contrast to oropharyngeal cancers, oral cancers and other HNSCCs infrequently harbor HPV.