Faculty Bibliography

BACKGROUND: Chemo-radiotherapy has become the standard of care for loco-regionally advanced head and neck cancers. Platinum based regimens are the most effective. Although benefits are proven with chemo-radiation, acute toxicities are markedly increased. The dose and delivery schedules of Cisplatin have ranged from intermittent higher dose [100 mg/m2] every 3 weeks to low dose [6 mg/m2] daily administration. At present there is no data indicating which regimen is superior. PURPOSE: To compare acute toxicities of two chemotherapy schedules for head and neck cancers. MATERIALS AND METHODS: A total of 83 head and neck cancer patients treated with two schedules of concurrent chemo RT were analyzed, retrospectively, for treatment toxicity. In group A [51 patients], chemotherapy [CT] was administered on week 1, 4 and 7 [cisplatin 100 mg/m2] over a period of 2-3 days. In group B [32 patients], CT was delivered weekly [cisplatin 40 mg/m2]. Radiotherapy dose was 7000 cGy in 35 fractions for definitive concurrent chemo-radiation and 6600 cGy in 33 fractions for adjuvant treatment. RESULTS: Group B patients had increased grade III skin and hematological toxicity, where as patients in group A had more pharyngeal toxicity. Treatment interruptions and percentage of weight loss were higher in group B. Weekly CT schedule had higher rate of severe mucositis, which was statistically significant on both univariate [P = 0.005] and multivariate [P = 0.007] analysis. CONCLUSIONS: Three weekly CT is less toxic than weekly. Weekly CT can be made more acceptable by reducing the dose and using feeding tubes for nutrition.

BACKGROUND: The sub-site predilection of head and neck squamous cell carcinoma (HNSCC) reflects the risk profile of a community and there are suggestions that these are changing over time. OBJECTIVE: To determine the change in head and neck cancer in rural and urban populations in India. METHODS: Cancer registry data of an urban and a rural population were reviewed over a period of 13 and 11 years, respectively. Age adjusted rates (AAR) and age specific incidence rates were used for data analysis. RESULTS: Oral cancers formed the majority of the head and neck cancers with a predilection for tongue, except in rural males, in whom the pharynx was the predominant sub-site. Overall there was a reduction in the incidence of HNSCC, which was more pronounced in urban females and rural males (p< .001). Among the sub-sites, oral cavity cancers showed a decreasing trend in urban females (p< .01) and rural males (p< .01). However, the trend was towards increase of incidence of tongue cancers. Pharyngeal cancer showed reduction in urban females (p< .01), whereas it increased in rural females. The recent increase in incidence of young adults with HNSCC reported in developed countries was not observed. CONCLUSIONS: Overall, incidence of HNSCC is reducing. This may be attributed to the decreased prevalence of tobacco use. The increase in incidence of tongue cancer may suggest factors other than tobacco and alcohol in its genesis.

Cyclooxygenase (COX) is involved in modulating inflammatory response through the synthesis of prostaglandins. The inducible isoform of the enzyme, COX-2, is overexpressed in some malignant and premalignant lesions. Several preclinical and clinical studies have reported COX-2 inhibition as an effective strategy for chemoprevention. Nonsteroidal anitinflammatory drugs (NASIDs) such as celecoxib, are the most widely investigated COX-2 inhibitors. The oil-soluble diallyl sulfides (DAS) include monosulfides (DAMS), disulfides (DADS) and trisulfides (DATS). They were found to be effective against canine and human tumors, the mechanism of which remains unresolved. We attempted a comparative evaluation of the antiproliferative effect of DAS in HEK 293T cells. The cells were treated with increasing concentrations of DAMS, DADS and DATS. There were significant differences between the IC50 values of DAMS, DADS and DATS. RT-PCR was performed and the expression of COX-2 was compared with that of b actin. DATS inhibited COX-2 gene expression significantly stronger than DAMS and DADS. The data are suggestive of antineoplastic effect of DAS, mediated by controlling COX-2 expression.

Bioresorbable implants (meshs and plates) are increasingly used in reconstructive craniofacial and skull base surgery. Usually these implants must be contoured to fit the complex craniofacial anatomy ex vivo; occasionally final contouring is performed in vivo and must be done without damaging surrounding structures (e.g., dura, brain). We report a precision method for in vivo contouring of bioresorbable implants using the Shaw hemostatic thermal scalpel

A number of controversies exist in the treatment of differentiated thyroid carcinoma with respect to the extent of surgery, use of radioactive iodine and post-operative thyroxine suppression. Recent recognition of prognostic factors has helped to assign patients, based on their risk profile, as being at high risk of developing recurrence. This has facilitated the development of a selective approach to therapy, thus, avoiding unnecessary treatment and reducing morbidity without compromising treatment outcome. This review attempts to evaluate the current concepts of management of differentiated thyroid carcinoma in the light of these new developments

HYPOTHESIS: Increased cell motility is a hallmark of cancer cells. Proteins involved in cell motility may be used as molecular markers to characterize the malignant potential of tumors. METHODS: Molecular biology and immunohistochemistry techniques were used to investigate the expression of a selected panel of motility-related proteins (Rho A, Rac 2, Cdc42, PI3K, 2E4, and Arp2) in normal, premalignant, and squamous cell cancer cell lines of human head and neck origin. To assess the clinical potential of these proteins as molecular markers for cancer, immunohistochemistry was performed on paraffin-fixed head and neck cancer specimens (n = 15). RESULTS: All six motility-associated proteins were overexpressed in the premalignant and squamous cell cancer cell lines relative to normal keratinocytes. Immunohistochemistry with Rho A and Rac 2 showed increased staining in areas of cancer but not in normal tissue. CONCLUSION: Proteins involved in cell motility can be used as markers for head and neck squamous cell carcinoma. The head and neck cell lines used in this study may be used as a model to further investigate cell motility. Molecular markers of motility could have a significant impact on the diagnosis and staging of cancers originating from differentiated non-motile cells

This retrospective study evaluated tumour volume, estimated by computed tomography (CT), as a predictive factor in carcinoma of the tongue. Tumour volume was measured from pretreatment CT scans of 20 consecutive patients, followed up for at least 3 years, and this measurement was compared with tumour volume estimated from pathological specimens. T-stage and CT-derived tumour volume were compared with the clinical and pathological status of the nodes, and with the outcome of treatment.The measurement of tumour volume derived from CT correlated well with measurements derived from pathological examination, and tumour volume also predicted overall treatment failure. The disease-specific survival rate was 100% for patients with low-volume tumours (<13 cc) compared with 79% for those with stage T1 and T2 tumours.CT is a reliable way of measuring the volume of tumours in carcinoma of the tongue, and tumour volume is useful adjunct to the clinical tumour-node-metastases staging system.

OBJECTIVES: Supraglottic laryngectomy is a well-established surgical therapy for selected carcinomas of the larynx and hypopharynx. Most compromised by this procedure and its variations is the laryngeal mechanism that protects the lower respiratory tract from aspiration. Laryngeal suspension serves to compensate for the loss of the resected laryngeal elevator muscles by pulling the larynx upward and forward beneath the tongue base. In this study we describe a method of laryngeal suspension in supraglottic laryngectomy using a cartilage-anchored suture carrier device. STUDY DESIGN: Report of this novel approach to laryngeal suspension using seven suture anchors in two patients undergoing supraglottic laryngectomy. METHODS: Seven Mitek Micro anchors (Mitek, Westwood, MA) were used to perform laryngeal suspension in two patients undergoing supraglottic laryngectomy. Our technique is compared with traditional methods. Operative data as well as postoperative functional results are reviewed. RESULTS: Laryngeal suspension using suture anchors was successful, with failure of only one anchor. Oral alimentation was quickly reestablished in both patients. There were no perioperative or postoperative complications. CONCLUSIONS: We describe a novel approach to laryngeal suspension that overcomes some of the technical challenges inherent in traditional suturing techniques. This novel approach is technically easier and more efficient than traditional methods and accomplishes distribution of stress forces on the thyroid cartilage remnant

BACKGROUND: The role of cytokines in tumor regression is now well established. The major limitation for the clinical use of cytokines is the lack of a simple and effective protocol for the local and sustained delivery of cytokines to the tumor milieu. This study reports suppression of human head and neck squamous cell carcinoma (HNSCC) by human peripheral blood lymphocytes (HuPBL) following local, sustained delivery of interleukin-12 (IL-12) to tumors with biodegradable microspheres in a human/SCID mouse chimeric model. Materials and Methods Nondisrupted biopsy pieces (120 mg) of primary HNSCC were implanted s.c. into severe combined immunodeficient (SCID) mice and were expanded by serial passage in mice. Tumors were then titrated with different doses of allogeneic HuPBL by coengraftment of tumor pieces and HuPBL into the subcutis of SCID mice to determine whether the HuPBL possessed antitumor activity (the SCID/Winn model). The lymphocyte subsets that were responsible for the suppression of tumor engraftment were identified by selective depletion of the CD4+, CD8+, and CD56+ cells from the HuPBL prior to engraftment into mice. Attempts were then made to augment the antitumor activity of the HuPBL either by repeated intralesional bolus injections of recombinant human IL-12 (0.5 &mgr;g x 10 doses) or with a single dose of IL-12-loaded microspheres ( approximately 1.65 &mgr;g IL-12/mg microspheres, 2 mg microspheres/mouse). RESULTS: Successful engraftment of HNSCC was observed in 12 of 19 different patient samples. Normal histological architecture of tumor was maintained up to four serial passages in the SCID mice. After the first tumor engraftment, but not in subsequent passages, human immunoglobulin produced by plasma cells present in the tumor infiltrating lymphocyte population was detected in the mouse sera. Allogeneic human PBL displayed antitumor cytotoxic activity in a cell dose-dependent fashion when coengrafted with the tumors passaged in SCID mice. Lymphocyte subset depletion studies established that tumor suppression was dependent on both the CD8+ T lymphocytes and the CD56+ natural killer cells. Treatment of tumors with a single intralesional injection of IL-12-loaded microspheres was highly effective, resulting in the complete suppression of tumor engraftment in 50% of the mice. In contrast, treatment of tumors with repeated bolus IL-12 injections suppressed tumor engraftment only transiently and did not result in complete tumor rejection in any of the mice. CONCLUSION: The coengraftment of HNSCC and allogeneic lymphocytes into SCID mice provides a viable model with which to evaluate immunotherapeutic strategies for human cancer. The use of biodegradable microspheres for local sustained delivery of cytokines to augment lymphocyte mediated antitumor immunity within the tumor microenvironment provides a safer and simpler alternative to current cytokine immunotherapy protocols.