Faculty Bibliography

Worldwide, the incidence of oral tongue cancer is on the rise, adding to the existing burden due to prevailing low survival and high recurrence rates. This study uses high-throughput expression profiling to identify candidate markers of resistance/response in patients with oral tongue cancer. Analysis of primary and post-treatment samples (12 tumor and 8 normal) by the Affymetrix platform (HG U133 plus 2) identified 119 genes as differentially regulated in recurrent tumors. The study groups had distinct profiles, with induction of immune response and apoptotic pathways in the non-recurrent and metastatic/invasiveness pathways in the recurrent group. Validation was carried out in tissues by Quantitative Real-Time PCR (QPCR) (n=30) and immunohistochemistry (IHC) (n=35) and in saliva by QPCR (n=37). The markers, COL5A1, HBB, IGLA and TSC individually and COL5A1 and HBB in combination had the best predictive power for treatment response in the patients. A subset of markers identified (COL5A1, ABCG1, MMP1, IL8, FN1) could be detected in the saliva of patients with oral cancers with their combined sensitivity and specificity being 0.65 and 0.87 respectively. The study thus emphasizes the extreme prognostic value of exploring markers of treatment resistance that are expressed in both tissue and saliva.

BACKGROUND: Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by osteomalacia, which occurs as a result of excess renal phosphate excretion caused by fibroblast growth factor-23 secreted by mesenchymal tumors. This entity is rare in head and neck cancers. We report a rare case of oncogenic osteomalacia in a patient with an anterior skull base giant cell tumor. METHODS AND RESULTS: A 34-year-old woman presented with a 5-year history of progressive weakness in both lower limbs and the trunk. Hypophosphatemia and hypocalcemia had been noted by a local physician, but her symptoms persisted despite receiving calcium and vitamin D supplements. A recent onset of epistaxis and nasal blockage led to referral to the head and neck services. Nasal endoscopy revealed a left nasal cavity mass. Further evaluation with imaging studies revealed a mass in the nasal cavity with intracranial extension. Biopsy of the lesion suggested a neurogenic tumor. A putative diagnosis of anterior skull base neurogenic tumor with paraneoplastic hypophosphatemia was made. After the biochemical parameters were corrected, the patient underwent craniofacial resection. The final histopathologic study suggested the lesion as a "giant cell tumor." During the postoperative period the patient's biochemical and clinical symptoms improved dramatically, allowing her to regain normal mobility. CONCLUSIONS: Clinicians and pathologists must be aware of the clinical symptoms, laboratory abnormalities, and pathologic features of oncogenic osteomalacia, which may be caused by tumors in the head and neck and thus make an exhaustive effort to diagnose the same.

OBJECTIVE: Transcutaneous "access" procedures still continue to be widely employed for surgical management of medium-sized (T2, T3) oral cavity tumors in spite of the almost 4-cm mouth opening available to the surgeon to access the oral cavity. We undertook a retrospective study to objectively evaluate "per oral access" in managing these tumors with regard to the ability to achieve a clear surgical margin and enable reconstruction of resultant defect. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic hospital. SUBJECTS AND METHODS: Seventy-nine consecutive patients of oral squamous cell carcinoma excised by per oral approach were analyzed. Multiple patient- and tumor-related factors known to influence status of surgical margins were analyzed. The overall frequency of clear, close, and involved margins was noted, as well as 5-year local control rate. The method of reconstruction employed was evaluated. RESULTS: The close/involved margins were more frequent with larger tumors and tumors exhibiting perineural infiltration, but none were statistically significant (P > .12). The overall frequency of clear, close, and involved margins was 81%, 11%, and 8%, respectively. Tongue and buccal mucosa sites constituted approximately 85% of the cases and had an 85% clear margin rate. Five-year local control rate was 70.35%. Fifty-three free flaps reconstruction were undertaken without any additional "access" procedure. CONCLUSION: Our results demonstrate ability to obtain comparable tumor clearance rates employing per oral access, without compromising ability to perform optimal reconstruction. We suggest per oral access should be the access of choice for medium-sized oral cavity tumors, and additional access procedures should only be considered if the initial access proves inadequate.

OBJECTIVE: Nodal metastasis from oral tongue squamous cell carcinoma follows a predictable pattern. Isolated level IV involvement, termed skip metastases, is described. This study attempts to identify the incidence of skip metastasis. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic hospital. SUBJECTS: Fifty-two consecutive patients with T1 to T4 N0 stage who underwent excision of the primary tumor with neck dissection (levels I-IV). METHODS: Retrospective study. The incidence of isolated level III or IV involvement pathologically and isolated nodal recurrence in levels III and IV was analyzed. RESULTS: Pathologically, isolated level III involvement occurred in 2 (3.8%) patients. Isolated level IV occurred in 1 (1.9%) patient. Mean follow-up was 24 months. Two patients had recurrence in the primary site; 1 had recurrence in neck level II. None had recurrence in level III or IV. CONCLUSION: Skip metastasis is rare in T1 and T2 oral tongue squamous cell carcinoma. Inclusion of level IV is not mandatory in selective neck dissection for clinically and radiologically negative neck disease in early tumors (T1 and T2).

Extensive and complex defects of the head and neck involving multiple anatomical and functional subunits are a reconstructive challenge. The purpose of this study is to elucidate the reconstructive indications of the use of simultaneous double free flaps in head and neck oncological surgery. This is a retrospective review of 21 consecutive cases of head and neck malignancies treated surgically with resection and reconstruction with simultaneous use of double free flaps. Nineteen of 21 patients had T4 primary tumor stage. Eleven patients had prior history of radiotherapy or chemo-radiotherapy. Forty-two free flaps were used in these patients. The predominant combination was that of free fibula osteo-cutaneous flap with free anterolateral thigh (ALT) fascio-cutaneous flap. The indications of the simultaneous use of double free flaps can be broadly classified as: (a) large oro-mandibular bone and soft tissue defects (n = 13), (b) large oro-mandibular soft tissue defects (n = 4), (c) complex skull-base defects (n = 2), and (d) dynamic total tongue reconstruction (n = 2). Flap survival rate was 95%. Median follow-up period was 11 months. Twelve patients were alive and free of disease at the end of the follow-up. Eighteen of 19 patients with oro-mandibular and glossectomy defects were able to resume an oral diet within two months while one patient remained gastrostomy dependant till his death due to disease not related to cancer. This patient had a combination of free fibula flap with free ALT flap, for an extensive oro-mandibular defect. The associated large defect involving the tongue accounted for the swallowing difficulty. Simultaneous use of double free flap aided the reconstruction in certain large complex defects after head and neck oncologic resections. Such combination permits better complex multiaxial subunit reconstruction. An algorithm for choice of flap combination for the appropriate indications is proposed.

BACKGROUND: Human papilloma virus (HPV) is an important risk factor for head and neck cancer, specifically oropharyngeal cancer, but its association with oral tongue squamous cell carcinoma (SCC) is uncertain. The objectives were to determine the HPV16 prevalence in oral tongue SCCs, its integration status and to correlate the expression of oncogenic proteins with targets. METHODS: In this case-control study with oral tongue SCC cases (n=60) and normal oral mucosa (n=46), HPV positivity was determined by polymerase chain reaction (PCR) using consensus and HPV 16 type specific primers and p16 immunohistochemistry (IHC). The viral integration status was determined with primers specific to the E2 gene and in situ hybridization (ISH). Immunohistochemical analysis of HPV oncogenic proteins (E6, E7) and their target proteins (p53, pRb, cyclinD1, p16, Notch-1, EGFR) proteins was carried out in HPV positive cases. The data was analyzed with SPSS software (v 11.0). Survival analysis was carried out by the Kaplan-Meier method. RESULTS: HPV16 was detected in 48% (n=29) of the cases and none of the controls by PCR assay (p<0.001) while p16 IHC, as a surrogate HPV marker, detected 33% (n=18) of the cases; 18% (n=10) were detected by both the methods. Integration was observed in 83% (n=24) by E2-PCR and 67% (n=18) by ISH. The E6-p53 pathway was active in 33% of the cases; E7-pRb in 52% and both in 11%. HPV positivity was associated with well-differentiated cancers (p=0.041) and low recurrence rate (p=0.014). CONCLUSION: Our study confirms a positive correlation of HPV infection with oral tongue cancer.

Oral cancer is a potentially preventable disease due to its association with well-known risk factors and easy detectability. There is a significant deficiency in the awareness of oral cancer and its risk factors among the public. Raising public awareness could effectively contribute to achieving a significant reduction in the incidence of oral cancer. The objective of this study was to evaluate the effectiveness of mouth self-examination (MSE) in improving the awareness of oral cancer and its risk factors as well as test its feasibility as an oral cancer-screening tool. The study was carried out in a high-risk population of 57,704 from India, of which, 34,766 individuals who have met the eligibility criteria formed the study population. MSE brochures and trained health workers were employed for the purpose of health education and cancer screening. The present study compared their efficacy to detect oral lesions. Subjects with suspicious lesions were referred to the trained oral cancer specialist for confirmation. A questionnaire to assess the awareness of oral cancer and its risk factors was developed and validated. SPSS (v.11.0) was used for data analysis. The program identified 216 cases of potentially malignant lesions as well as three cases of oral cancer. The findings of MSE and health workers showed 72% concordance, while that of health workers and oral cancer specialist showed 100% concordance. MSE had a low sensitivity of 18%, while the specificity was 99.9%. Though the technique identified high-risk lesions such as red patches (66.7%) and non-healing ulcers (42.9%), the detection rate of white patches was low (12.7%). Overall awareness of oral cancer and its risk factors after introduction of MSE program was over 80%; but the compliance to seek treatment was poor (32%). Mouth self-examination may be used as an effective tool to improve the awareness of oral cancer and for the early detection of lesions.

Composite defects of oral cavity are a reconstructive challenge. Anterolateral thigh flap provides large and pliable tissue for reconstruction of these defects. However, wide variations in the vascular anatomy, variable perforator number and location are reported. The aim of this study was to evaluate the reliability of single perforator based large anterolateral thigh for reconstruction of complex oral cavity defects following ablative surgery. We report a series of 25 consecutive patients who underwent reconstruction of oral cavity defects with anterolateral thigh flap based on single perforator between August 2009 and August 2010. The mean flap dimension was 261cm(2) (range 80-540cm(2)). In 21 patients the flap was bi-paddled and used for inner and outer lining for cheek. None of the flaps developed perforator insufficiency. Two flaps were lost due to delayed neck wound sepsis after 7th post operative day. This study establishes safety and reliability of using a large and/or bi-paddled anterolateral thigh flap based on single perforator for reconstruction of complex oral cavity defects.

Poorly differentiated carcinomas of the thyroid have evolved over the past half century into a specific entity in the classification of thyroid carcinomas. The need for a consensus diagnostic criteria has been stressed in view of the wide discrepancies and confusion among pathologists and clinicians. This review attempts to understand the concept, the evolution, clarity and validity of the concepts in poorly differentiated carcinomas of the thyroid.

The purpose of this study was to report the effectiveness of the lateral arm free flap (LAFF) in the reconstruction of oral tongue defects, the subsite in which it may have advantage over the other donor sites. This is a retrospective analysis of 48 consecutive cases of LAFF used for the reconstruction of partial glossectomy defects for squamous cell carcinoma of the oral tongue. Primary defect and donor-site morbidity and the functional and aesthetic outcomes were assessed in 37 evaluable patients, with a minimum of 6 months follow-up. Patient-reported Visual Analog Scale score from 0 (minimum satisfaction) to 10 (maximum satisfaction) was used to evaluate the aesthetic outcome. The follow-up was for 6 to 52 months (mean, 24 months). The flap was successful in 45 (93.8%) patients. The commonest observed donor-site morbidity was a broad scar, but it did not cause much patient dissatisfaction because it could be covered with appropriate dressing. Speech was normal or near-normal in all patients. Poor functional outcome was associated with adjuvant postoperative radiotherapy. The visual analog scale score for the aesthetic satisfaction (mean [standard deviation]) was 6.58 (1.82) for primary site and 7.13 (1.99) for the donor site. LAFF is an excellent option for the reconstruction of partial glossectomy defects of oral tongue without significant involvement of the floor of mouth and base of tongue.