Olsen, Kerry D.

Objectives/HypothesisAssess the role of retropharyngeal lymph node dissection in oropharyngeal squamous cell carcinoma treated with transoral robotic surgery (TORS).Study DesignProspective case series.MethodsRetrospective analysis of 72 patients with oropharyngeal squamous carcinoma treated with transoral oropharyngectomy, neck dissection, and retropharyngeal node dissection.ResultsEight of 55 (14.5%) patients with tonsil primaries had retropharyngeal metastases in contrast to none with tongue base primaries. The presence of pathologically positive retropharyngeal nodes was associated with clinical tumor (T) (P=.002) and node (N) stage (P=.007), preoperative computed tomography (CT) (P<.001), and positron emission tomography (PET)‐CT scan (P<.001). The negative predictive value of early T (Tx,1‐2) and N stage (N0‐N2a) was 91.7% and 100%, respectively. Preoperative CT and PET‐CT both yielded a positive predictive value of 100%, while the negative predictive value of imaging was optimized to 95.3% when these modalities were combined.ConclusionsIn patients with tonsil cancer the risk of retropharyngeal metastases is negligible in the presence of clinically T1‐2, N0‐N2a disease and negative CT and PET‐CT. We estimate that 40% of patients meet these criteria and may safely forego treatment of the retropharyngeal nodes. Approximately 10% of patients will have positive imaging and we recommend retropharyngeal node dissection at the time of surgery to treat macroscopic disease. In the remaining patients at risk for retropharyngeal node involvement, adjuvant radiotherapy is generally indicated based on other adverse features, and these nodes may be incorporated into the treatment field.Level of Evidence4. Laryngoscope, 2013

Abstract Chromosome rearrangements that result in gene fusions have important roles in the initial steps of tumorigenesis especially in leukemias and lymphomas, but the biological and clinical impact of gene fusions in the common solid tumor has been less appreciated. We previously generated RNAseq data from 12 oropharyngeal tumors along with matched normal tissue from the same patients. We utilized and compared two bioinformatic pipelines, SnowShoes-FTD and FusionHunter to identify two novel fusion events involving of MGST3-ZMAT5 and MS4A7-DKFZp586P0123. These fusions were validated utilizing. Reverse transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing validated. In the first translocation the 5′ UTR of MGST3 was fused with exon 1 of ZMAT5, and in the second translocation the exon 2 of MS4A7 was fused with 3′ UTR of DKFZp586P0123. These precise fusions were not present in the matched normal tissue, however, they were only found in the single tumor in which they were identified. Given a growing and powerful set of high-throughput massively parallel sequencing technologies, the future for genome-wide analysis of chromosome rearrangement appears open in many directions. Ultimately, we hope that this integrative methodology will elucidate key aspects of tumor biology as well as generate novel targets for cancer diagnostics and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3100. doi:1538-7445.AM2012-3100

Abstract There is considerable clinical interest in the role that human papillomavirus (HPV) plays in the development of oropharyngeal cancers. A variety of assays are currently available to stratify patients based on HPV status prior to treatment. The most frequently utilized are PCR and In Situ hybridization (ISH) to detect the presence of HPV DNA sequences. The increasing clinical interest in determining HPV patient status relates to compelling evidence that a subset of patients with HPV positive tumors have better clinical outcomes. Evidence also suggests that patients with HPV positive tumors should be further divided into groupings based on levels of viral activity and that this may represent additional clinical information necessary to develop appropriate treatment plans. The most frequently applied assay to identify HPV activity in a patient sample is to detect the over-expression of the surrogate protein marker p16 by Immunohistochemisty (IHC), which has been shown to increase expression in response to HPV active infections in oropharyngeal cancer. An alternative technique to quantitatively detect the presence and level of transcriptional activity of HPV in tissue samples is to measure the expression of oncogenes E6 and E7. We have analyzed the fresh frozen tissue samples corresponding to matched tumor, normal and metastatic patient tissues using a quantitative PCR (qPCR) approach to determine the expression of HPV oncogenes and p16 gene expression. We observed that there are three groups of oropharyngeal tumors when grouped by HPV16 E6 and E7 gene expression. The first are the most rare and are tumors that contain no HPV sequences or expression of the E6 and E7 ocogenes. The second are tumors that contain HPV DNA sequences but very low expression of E6 or E7 and the third are tumors that contain HPV DNA sequence and robust expression of E6 and E7. Additionally, we found variable correlation between HPV16 E6 and E7 expression and p16 gene expression, suggesting that factors other than HPV oncogene expression may influence the expression of p16. Our results would indicate that the best assays for quantifying the activity of an HPV infection in oropharyngeal cancers would be those optimized to accurately measure either E6 and E7 transcripts or their protein products directly out of paraffin-embedded tissues. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3859. doi:10.1158/1538-7445.AM2011-3859

ObjectivesTo determine the cost of treatment of oropharyngeal squamous cell carcinoma (OP SCCA) with transoral surgery with concomitant neck dissection (TOS), TOS with adjuvant radiation therapy (TOS + RT), TOS with adjuvant chemoradiation therapy (TOS + CRT), and primary chemoradiation therapy (CRT).Study DesignCase series.SettingTwo tertiary care teaching hospitals.Subjects and MethodsUsing the databases of 2 teaching hospitals, patients were identified who had OP SCCA treated with TOS, TOS + RT, TOS + CRT, and primary CRT in 2009 to 2010. Costs were analyzed from an institutional perspective looking at reimbursement. Patients with government payers and patients with private payers in each group were identified, and net revenue data obtained for the 3‐month period from diagnosis were calculated and averaged for each group. Cost was defined as the reimbursement for all charges surrounding the 3‐month episode of treatment. All revenue associated with inpatient and outpatient care, including pharmacy charges, was included.ResultsThe mean cost of TOS (private payers/government payers) was $37,435/$15,664 (range, $22,486‐$48,746/$13,325‐$16,885). The mean cost of TOS + RT (private payers/government payers) was $74,484/$34,343 (range, $72,400‐$84,825/$31,565‐$40,810). The mean cost of TOS + CRT (private payers/government payers) was $191,780/$53,245 (range, $145,450‐$217,220/$49,400‐$58,325). The mean cost of CRT (private payers/government payers) was $198,285/$57,429 (range, $168,216‐$298,945/$52,900‐$59,545).ConclusionAn algorithm of transoral surgical treatment of OP SCCA with adjuvant treatment as indicated by pathology is more cost conscious than an algorithm of treatment of all OP SCCA with CRT.

AbstractIt has been well established that a high level of stress is associated with medical problems, mental health difficulties and absenteeism at the workplace. The aim of this single‐arm study design was to examine the potential effectiveness of a 12‐session multidisciplinary stress reduction programme on reducing perceived stress and improving health behaviours and quality of life. One hundred and four women participated in a programme that incorporated group support, skill building and cognitive behavioural and relaxation techniques. A series of Bonferroni corrected t‐tests found that the participants reported having significantly (p < 0.001) lower levels of perceived stress, improved health behaviours (sleep, nutrition, physical activity) improved overall health and improved quality of life at the end of the 12 week programme and at 1‐month follow‐up. Although the effect sizes for improvement were all large, there was no control group, so regression to the mean or selection bias may have impacted the results. Therefore, these results provide initial support for the implementation of gender‐based worksite stress reduction programmes and provide guidance in designing an effective worksite stress reduction programme. Further research using randomized controlled trials is warranted. Copyright © 2011 John Wiley & Sons, Ltd.

Abstract Cancers of the head and neck rank as the 6th most commonly observed cancers worldwide with an average 5-year survival rate of only 50% for advanced disease. Nearly 95% of head and neck cancers are squamous cell carcinomas (SSC) and these are frequently highly invasive metastatic tumors. The newly developing technologies of Next Generation Sequencing have allowed for the most comprehensive genetic analysis of these cancers to date. We have taken 3 tumor/normal pairs from patients with oral squamous cell carcinoma and performed full transcriptome and mate-pair DNA sequencing analysis using the AB SOLiD system. These runs generated 129-256 million 50bp long sequence reads per sample, with 21 to 56 million reads per sample uniquely aligning to human genome sequence. Analysis of these samples has revealed pathways with aberrant expression in tumor versus normal tissue. Our results show up-regulation of some metalloproteinase genes, HGMA2, which is a prognostic marker for oral carcinoma, and extracellular matrix, adhesion, and motility gene classes in tumors. Our functional analysis also indicates extensive down-regulation, in the tumors, of genes functioning in epidermal development. We were also able to measure allelic specific expression for the 50% most highly expressed genes and detect examples of allelic imbalance linked to pathways with dysregulated gene expression. Additionally, the depth of sequencing that was achieved (5-16X coverage of RefSeq Exons) also allowed us to detect mutations occurring in the transcripts. We have also detected evidence of RNA editing associated with point mutations, which we are validating in a larger group of samples. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2957.

OBJECTIVETo review the Mayo Clinic experience with sinonasal melanoma.STUDY DESIGNRetrospective review (case series).SUBJECTS AND METHODSWe identified 61 patients who had melanoma arising from the nasal cavity, paranasal sinuses, or both. All were treated at our institution from 1955 through 2003. Clinical and pathologic data were summarized, and survival curves were generated.RESULTSThe most common symptoms at presentation were epistaxis and nasal congestion. The most common treatment was excision only (48%). The cancer‐specific survival rate (ie, rate of death due to disease) was 48.9% and 22.1% at 3 and 5 years, respectively. Median time between diagnosis and death due to disease was 19 months.CONCLUSIONSinonasal melanoma is a rare but devastating disease. Wide local excision is the treatment of choice, and some patients may benefit from postoperative radiotherapy. Local recurrence and distant metastasis are common. Improved survival depends on better systemic therapies.

Intranasal sphenoethmoidectomy is one of the most frequently performed operations in otorhinolaryngology. Surgical indications and techniques have evolved with advances in medical technology. Clinical reports describing complications relating to sphenoethmoidectomy, either by traditional or endoscopic technique, have elucidated the potentially dangerous nature of this procedure. 1–6 Intraoperative complications are avoided through a detailed knowledge of anatomy and a technique guided by structural landmarks. We present a case of sphenoethmoidectomy complicated by cerebrospinal fluid (CSF) rhinorrhea and a nasal encephalocele.