Citations

Object Swallowing dysfunction is common following transoral (TO) odontoidectomy. Preliminary experience with newer endoscopic transnasal (TN) approaches suggests that dysphagia may be reduced with this alternative. However, the reasons for this are unclear. The authors hypothesized that the TN approach results in less disruption of the pharyngeal plexus and anatomical structures associated with swallowing. The authors investigate the histological and gross surgical anatomical relationship between pharyngeal plexus innervation of the upper aerodigestive tract and the surgical approaches used (TN and TO). They also review the TN literature to evaluate swallowing outcomes following this approach. Methods Seven cadaveric specimens were used for histological (n = 3) and gross anatomical (n = 4) examination of the pharyngeal plexus with the TO and TN surgical approaches. Particular attention was given to identifying the location of cranial nerves (CNs) IX and X and the sympathetic chain and their contributions to the pharyngeal plexus. S100 staining was performed to assess for the presence of neural tissue in proximity to the midline, and fiber density counts were performed within 1 cm of midline. The relationship between the pharyngeal plexus, clivus, and upper cervical spine (C1-3) was defined. Results Histological analysis revealed the presence of pharyngeal plexus fibers in the midline and a significant reduction in paramedian fiber density from C-2 to the lower clivus (p < 0.001). None of these paramedian fibers, however, could be visualized with gross inspection or layer-by-layer dissection. Laterally based primary pharyngeal plexus nerves were identified by tracing their origins from CNs IX and X and the sympathetic chain at the skull base and following them to the pharyngeal musculature. In addition, the authors found 15 studies presenting 52 patients undergoing TN odontoidectomy. Of these patients, only 48 had been swallowing preoperatively. When looking only at this population, 83% (40 of 48) were swallowing by Day 3 and 92% (44 of 48) were swallowing by Day 7. Conclusions Despite the midline approach, both TO and TN approaches may injure a portion of the pharyngeal plexus. By limiting the TN incision to above the palatal plane, the surgeon avoids the high-density neural plexus found in the oropharyngeal wall and limits injury to oropharyngeal musculature involved in swallowing. This may explain the decreased incidence of postoperative dysphagia seen in TN approaches. However, further clinical investigation is warranted.

The common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. The frequent deletions and other alterations in these regions in multiple cancers has led to the discovery of a number of extremely large genes contained within these regions and several of the large CFS genes have already been demonstrated to function as tumor suppressors involved in the formation of many different cancers. To study the large CFS genes in oropharyngeal squamous cell carcinoma (OPSCC), we did RNA seq analysis from 11 head and neck cancer patients. This revealed that there are six large CFS genes which consistently had decreased expression in the tumor samples compared to their matched normal tissues. These six genes are PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT. PARK2 and FHIT are located within the two most frequently expressed CFSs and both have been demonstrated to function as tumor suppressors, while the other large genes are found to have frequent alterations in multiple cancers. Validation experiments using real time PCR indicated that over 60% of OPSCC tumors showed decreased expression for all six genes. Both HPV‐positive and HPV‐negative OPSCCs had similar proportions with loss of expression of these genes. Our results suggest that this selected group of large genes might serve as potential tumor suppressors involved in the development of OPSCCs. Further studies are needed to investigate whether the decreased expression observed is due to genomic instability within the CFS regions or the selection for alterations of specific large CFS genes. © 2014 Wiley Periodicals, Inc.

AbstractBackgroundIntense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse.MethodsFrom 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post‐reoperative disease outcomes, reasons for relapse, and complications.ResultsBilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II–V dissection, 93 (23 %); levels III–V, 86 (21 %); lateral single‐ or two‐compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow‐up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre‐reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %).ConclusionsAlthough 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15–20 %; at least 20 % reflect the biologic aggressiveness of the disease.

Objectives/HypothesisTo determine the incidence of level IIB lymph node metastasis in patients with laryngeal or hypopharyngeal squamous cell carcinoma and to evaluate the need for elective and therapeutic neck dissection of level IIB.Study DesignRetrospective cohort study and review of the literature.MethodsPatients with laryngeal or hypopharyngeal squamous cell carcinoma (N = 65) were primarily treated with surgery at Mayo Clinic (Rochester, Minnesota) from 2004 through 2010. Neck dissection specimens were analyzed by a pathologist, and metastases to level IIB were reported. In addition, 18 previously published studies, totaling 1,114 neck dissections, were reviewed.ResultsLevel IIB lymph node metastases were present in 4% and 17% of elective and therapeutic neck dissections, respectively. Ipsilateral IIB metastasis was more common than contralateral IIB metastasis in elective and therapeutic neck dissection specimens. Level IIB lymph node metastasis was not significantly associated with level IIA nodal metastasis, level III nodal metastasis, clinical primary tumor stage, clinical nodal stage, or pathologic confirmation of extracapsular spread in either laryngeal or hypopharyngeal squamous cell carcinoma.ConclusionsThe rate of occult IIB metastasis in laryngeal and hypopharyngeal squamous cell carcinoma is exceedingly low. In a clinically node‐negative case, the ipsilateral and contralateral level IIB nodal packet should not be dissected. For clinically node‐positive cases, ipsilateral level IIB dissection should be performed; contralateral IIB dissection should be performed only when indicated.Level of Evidence4. Laryngoscope, 123:3032–3036, 2013

Objectives/HypothesisTo determine the incidence of level IIB lymph node metastasis in patients with oropharyngeal squamous cell carcinoma (OPSCC) and to evaluate the necessity of level IIB dissection for elective and therapeutic neck dissections.Study DesignRetrospective cohort study.MethodsPatients with OPSCC (N = 348) were surgically managed at our institution from 2004 through 2010. Neck dissection specimens were reviewed by a pathologist, and level IIB metastases were analyzed with respect to clinical and pathologic data.ResultsLevel IIB lymph node metastases were present in 2.5% and 25% of elective and therapeutic neck dissections, respectively. Level IIA metastasis, clinical tumor stage, clinical nodal stage, extracapsular spread, and primary tumor location in the tonsil were significantly associated with level IIB metastasis.ConclusionsThis study uniquely demonstrated a statistically significant association between clinical tumor stage and tonsil subsite with level IIB metastasis in OPSCC. Considering the predicted incidence of nodal metastasis, we conclude that level IIB neck dissection can be omitted in early stage (T1 or T2) clinically node negative (cN0) OPSCC. In patients with a cN0 neck and advanced OPSCC (T3 or T4), primary tumor in the tonsil, or ipsilateral clinically node positive (cN+) and contralateral cN0 neck, level IIB dissection should be considered. Level IIB dissection should be performed routinely in patients with cN+ OPSCC.Level of Evidence4. Laryngoscope, 123:2700–2705, 2013

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

The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.

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.