Peter H. Rhys Evans

Radiation induced sarcoma of the head and neck.

Radiation‐induced sarcoma of the head and neck (RISHN) is a long‐term complication of treatment. The rarity of this tumour is reflected in the very few series reported in the English language medical literature. The incidence of RISHN is, however, likely to increase due to progressive aging of the population combined with improved survival in head and neck cancer patients resulting from better treatment regimes. Diagnosis and management of this problem can be extremely challenging and the overall outlook has been reported to be very bleak. As survival data from isolated case reports cannot be expected to provide reliable information on outcome, we have reviewed 69 cases reported in the English medical literature since 1966 and pooled this information with our experience in treatment of RISHN.

Cross-links between stereocilia in the human organ of Corti.

Human cochleae were fixed in glutaraldehyde, without the use of osmium. Cross-links were seen between the stereocilia, similar to those we have previously reported for the guinea pig: first, stereocilia of the same row on each hair cell were joined by horizontally-running links; secondly, the shorter stereocilia had pointed tips, each giving rise to a single, vertically-pointing link, which ran upwards to join the adjacent taller stereocilium of the next row. We suggest that distortion of this link is involved in sensory transduction. The links were sparser than had been seen in the guinea pig which may be a reflection of the vulnerability of the links to non-optimal fixation, and the greater difficulty in producing good fixation in human specimens.

Intralaryngotracheal thyroid--ectopic thyroid or invasive carcinoma?

Intralaryngotracheal thyroid is a rare clinical condition with only about 125 cases described so far in the literature. We present an unusual case of intralaryngotracheal thyroid which had many clinical features of malignancy and yet appeared benign on histology. As in this case, well-differentiated thyroid cancer can present with locally aggressive clinical features and can pose a dilemma in management if treatment decisions are guided solely by histological features.

Liposarcoma of the thyroid gland mimicking retrosternal goiter

Primary liposarcoma of the thyroid gland is extremely rare with only two previous reports in the literature. We report two further cases, both patients presenting with rapid airways compression. Patient 1 had clinical, radiographic, and biopsy appearances suggesting benign goiter. Patient 2 had a long-term history of benign goiter, a previous partial thyroidectomy, and more recent biopsies showing liposarcoma. The management of such rare conditions is always challenging.

Electroglottographic analysis of valved speech following total laryngectomy.

Twenty-seven total laryngectomy patients (19 males and 8 females) and 18 normal control subjects (10 males and 8 females) were subjected to electroglottography-based single voice recordings using sustained vowels and connected speech. The results showed poorer values and larger variability for all the voice measures for the total laryngectomy patients (TO speech) as compared to that of normal subjects. There were statistically significant differences (p<0.05) for all study parameters between the TO and normal speech. This study shows that robust and reliable data can be obtained using electroglottography in laryngectomees with both a sustained vowel and connected speech. Using these parameters, TO speech is significantly different from normal speech and is highly variable. This methodology has enormous potential for further investigations in laryngectomees and other patients with head and neck cancer.

Abstract LB-58: Angiogenic signaling is upregulated in human oral squamous carcinoma cells with acquired resistance to the EGFR inhibitor gefitinib

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Tyrosine kinase inhibitors (TKIs) have improved the therapeutic options for patients with EGFR-driven tumors; however initially responsive patients frequently relapse whilst on therapy. To investigate acquired resistance to EGFR TKIs we developed and characterized in vitro and in vivo models of gefitinib-resistance through chronic drug exposure of a squamous carcinoma cell line, CAL-27. The derived CALR subline showed 166-fold resistance to gefitinib compared with CALS cells (drug-sensitive controls). Constitutive levels of EGFR were unchanged but phospho-EGFR was reduced and phospho-AKT increased in CALR cells. No upregulation of MET or IGF-1R signalling pathways, previously reported in acquired resistance to EGFR TKIs, was seen. The growth rate and vascularisation of CALR xenografts was significantly greater than CALS, although in vitro proliferation rates were similar, observations recapitulated in a second, independently-derived gefitinib-resistant cell line. We thus hypothesised that the differential in vivo growth may be attributed to differences in angiogenic signalling between gefitinib-sensitive and -resistant tumors. To test this hypothesis we examined the expression of HIF1α (hypoxia-inducible factor 1α) a key mediator of tumor angiogenesis through transcriptional regulation of angiogenic factors, most notably VEGF-A. Here we present the novel finding that HIF1α is constitutively upregulated in gefitinib-resistant CALR cells in normoxia in vitro, and in xenograft tumors. This is accompanied by a concomitant increase in constitutive VEGF-A secretion from the resistant cells determined by ELISA, demonstrating that HIF1α is transcriptionally active. Multiplex antibody arrays (Proteome Profiler™, R&D Systems) were used to assess the expression of 55 angiogenesis-related proteins in gefitinib-sensitive and -resistant cells. Membranes spotted with capture antibodies were incubated with lysates or mouse sera and signals from a chemiluminescent substrate were quantified by densitometry using ImageQuant software (Nonlinear Dynamics). We identified 22 angiogenic proteins differentially expressed between CALS and CALR cells in vitro, several of which are transcriptionally regulated by HIF1α. These include pro-angiogenic factors upregulated in the CALR cells such as VEGF-A (confirming ELISA data) whilst a number of anti-angiogenic proteins were down-regulated, two of which were independently identified in xenograft-bearing mouse sera. In summary, using our model of gefitinib-resistant squamous carcinoma we have identified HIF1α as a potential novel mediator of gefitinib resistance and, with the aid of novel antibody array technology, have identified angiogenesis-related molecules not previously reported to associate with EGFR TKI acquired resistance. Together these data support our hypothesis that increased signalling via the EGFR-HIF-AKT axis is associated with the acquisition of resistance to gefitinib in oral squamous carcinoma. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 LB-58.

Principles and Practice of Head and Neck Surgery and Oncology, Second Edition

The first edition of this book was published in 2003. The editors state that this latest edition ‘‘has been thoroughly updated by a team of world leading head and neck surgeons, oncologists and allied healthcare professionals.’’ The book is current, involves more than 70 contributors, and is well illustrated with a large number of color pictures that account for its relatively high price. The book appears to be directed toward surgeons, based upon the titles and affiliations of the authors and the content. The book describes surgical techniques for various head and neck subsites that may be of limited interest to the nonsurgeon reader. Moreover, although the book aims at being ‘‘a comprehensive evidence-based account of the current scientific knowledge about head and neck tumors and their management,’’ unfortunately, we lack ‘‘evidence’’ for much of our daily clinical practice, and in this volume, surgical treatment is emphasized over other treatment modalities. However, with this in mind, there is no question that this book is a valuable resource, even for the nonsurgeon who wants to know more about surgery or seeks another viewpoint. The book is organized into three parts: general principles, treatment approach by subsite, and complication/reconstruction/rehabilitation issues. The first part, on general principles, is comprehensive and sufficiently detailed for both the student and the practitioner. The chapters on molecular biology, anesthesia, chemotherapy, nursing, nutritional support, and dental management of the head and neck cancer patient are clear and exhaustive. In my opinion, the chapter on imaging is too limited and concise, although this reflects the extent of the topic. Nevertheless, some issues, like the role of positron emission tomography/computed tomography (PET/CT) in reevaluat-

A restrospective analysis of surgery for the oral cavity and oropharyngeal squamous cell carcinoma

Abstract Objectives: To conduct a multifactorial analysis of patients with oral cavity and oropharyngeal squamous cell carcinoma surgically treated at the Royal Marsden Hospital. Methods: This is a 20-year retrospective analysis (1983–2003) with reference to site, age, gender, surgical approach, survival, etc. Results: There were 306 patients (251 fresh and 55 recurrent cases) with oral cavity and oropharyngeal squamous cell carcinomas (oral cavity, 203; oropharynx, 100; unknown, 3). Of these, 202 patients were male and 104 were female (M:F = 1.9:1) patients. Mean age at diagnosis was 57 years. The subsite distribution was as follows: oral cavity, T-125, BM-39, FOM-39; oropharynx, LW-65, AW-23, PW-6, and SW-6. An external surgical approach was performed in 196 cases and a peroral approach in 120 cases. A mandibulectomy was done in 47 cases (hemimandibulectomy, 27; segmental mandibulectomy, 9; and marginal mandibulectomy, 11) and glossectomy in 129 patients (partial, 71; hemi, 37; subtotal, 3; and total, 18). Two hundred eleven patients were subjected to radiotherapy (radical, 113; postop, 93; palliative, 5, and iridium implants, 4). Locoregional recurrence occurred in 95 patients with distant metastasis in 20 patients. Overall cause-specific survival at 1, 3, and 5 years was 86%, 66%, and 61%, respectively. Conclusions: Minimizing morbidity while ensuring good oncologic tissue margins with any approach to the oral cavity and oropharynx is difficult, but it is imperative. When factors were considered singly, poor prognosis was associated with late stage postop radiotherapy and external surgical approach. The effect of metastasis during follow-up was associated with a poor prognosis for survival. Nodal status and age were not significant predictors of survival.