Faculty Bibliography

BACKGROUND: Chemoradiotherapy is an established strategy for organ preservation in head-neck cancer. These protocols are associated with added toxicity and need support infrastructure. Practice setup and availability of resources vary at the community level in developing countries. AIM: To evaluate the feasibility of organ-preservation strategies in different settings in developing countries. SETTINGS AND DESIGN: Survey. MATERIALS AND METHODS: In a questionnaire-based study, questions were directed to clinicians with varied practice setups to gather information regarding infrastructure, finance, and feasibility of organ-preservation protocols and their current practice trends. STATISTICAL ANALYSIS: Descriptive. RESULTS: Responses from 100 clinicians with focused practice in head-neck oncology were analyzed. Sixty-one percent clinicians were practicing organ preservation for advanced head-neck cancers in their practice. However, 65% centers lacked sufficient infrastructure to support organ-preservation protocols. Forty percent patients were treated on cobalt-radiotherapy machine. Fifty-nine percent of clinicians suggested that less than third of their patients were fit to undergo chemoradiation and 67% believed that adherence to treatment protocol was observed in less than two-thirds of cases. Based on their experience 82% clinicians felt that only one-third patients requiring salvage would actually undergo treatment. The majority of the patients (68%) used personal funds for treatment and less than one-third of the patients could afford complete treatment. CONCLUSIONS: The infrastructure needed to support organ-preservation protocols varies significantly between centers in developing countries. It may not be feasible to perform organ-preservation strategies in certain centers and feasibility guidelines should be made for their judicious use in developing countries.

BACKGROUND: In a large and diverse country like India, there is a wide variation in the availability of infrastructure and expertise to treat head-neck cancer patients. Lack of consistent adherence to evidence-based management is the biggest problem. Aims: There is an unmet need to evaluate the existing treatment practices to form the basis for development of effective and uniform treatment policies. SETTINGS AND DESIGNS: Prospective case series. MATERIALS AND METHODS: A group of previously treated, potentially curable patients presenting to our institution (from April 2009 to March 2011) were evaluated for appropriateness of initial treatment based on National Comprehensive Cancer Network or Tata Memorial Hospital guidelines. Data regarding treatment center, protocol and accuracy of delivered treatment and their eventual outcome were analyzed. STATISTICAL ANALYSIS: Descriptive. RESULTS: Amongst 450 newly registered patients, 77(17%) were previously treated with curative intent and 69(89%) of them were inappropriately treated. Seventeen (25%) patients were treated in clinics while 12(17%) in cancer centers and 34(50%) in corporate hospitals. Fourteen (20%) patients received chemotherapy, 22(32%) received radiotherapy and 14(20%) underwent surgery while 19(28%) patients received multimodality treatment. Disease stage changed to more advanced stage in 40(58%) patients and curative intent treatment could be offered only to 33(48%) patients. Amongst 56 patients available for outcome review, 18(32%) patients were alive disease-free, 20(36%) had died and 18(32%) were alive with disease. CONCLUSION: Large numbers of potentially curable patients are inappropriately treated and their outcome is significantly affected. Many initiatives have been taken in the existing National Cancer Control Program but formulation of a uniform national treatment guideline should be prioritized.

The key factor mitigating against prognosis in head and neck cancer is nodal metastasis and its management. Neck dissection has been known to play an integral part in this type of cancer management. Submandibular gland preservation during neck dissection and post radiotherapy, have been known to improve subjective symptoms of xerostomia. The authors retrospectively surveyed the involvement of submandibular gland involvement in oral cancer with a view to confirm oncologic safety of submandibular gland preservation, as a first step in a quest to manage radiation induced xerostomia by submandibular gland transfer. The medical and pathological records of oral cancer patients who underwent surgical treatment at the authors' centre were reviewed retrospectively. 194 patients were included in the study. 229 submandibular glands were excised from the same number of neck dissections. 3 (1.3%) submandibular glands were involved with malignancies microscopically. The mode of involvement was by direct infiltration. In conclusion, no metastasis to submandibular gland was observed. This may suggest the oncologic safety of submandibular gland preservation and transfer.

The aim of this study was to evaluate factors affecting the selection of pectoralis major flap in the era of free tissue reconstruction for post ablative head and neck defects and flap associated complications. The records of patients who underwent various reconstructive procedures between July 2009 and December 2010 were retrospectively analysed. 147 reconstructive procedures including 79 free flaps and 58 pectoralis major flaps were performed. Pectoralis major flap was selected for reconstruction in 21 patients (36%) due to resource constrains, in 12 (20%) patients for associated medical comorbidities, in 11 (19%) undergoing extended/salvage neck dissections, and in 5 patients with vessel depleted neck and free flap failure salvage surgery. None of the flaps was lost, 41% of patients had flap related complications. Most complications were self-limiting and were managed conservatively. Data from this study suggest that pectoralis major flap is a reliable option for head and neck reconstruction and has a major role even in this era of free flaps. The selection of pectoralis major flap over free flap was influenced by patient factors in most cases. Resource constraints remain a major deciding factor in a developing country setting.

Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome characterized by bilateral vestibular schwannomas (VS) which often result in deafness despite aggressive management. Meningiomas, ependymomas, and other cranial nerve and peripheral schwannomas are also commonly found in NF2 and collectively lead to major neurologic morbidity and mortality. Traditionally, the overall survival rate in patients with NF2 is estimated to be 38% at 20 years from diagnosis. Hence, there is a desperate need for new, effective therapies. Recent progress in understanding the molecular basis of NF2 related tumors has aided in the identification of potential therapeutic targets and emerging clinical therapies. In June 2010, representatives of the international NF2 research and clinical community convened under the leadership of Drs. D. Gareth Evans (University of Manchester) and Marco Giovannini (House Research Institute) to review the state of NF2 treatment and clinical trials. This manuscript summarizes the expert opinions about current treatments for NF2 associated tumors and recommendations for advancing therapies emerging from that meeting. The development of effective therapies for NF2 associated tumors has the potential for significant clinical advancement not only for patients with NF2 but for thousands of neuro-oncology patients afflicted with these tumors.

OBJECTIVES/HYPOTHESES: The objective was to assess the utility of selected "resonant voice" (RV) exercises for the reduction of acute vocal fold inflammation. The hypothesis was that relatively large-amplitude, low-impact vocal fold exercises associated with RV would reduce inflammation more than spontaneous speech (SS) and possibly more than voice rest. STUDY DESIGN: The study design was prospective, randomized, and double blind. METHODS: Nine vocally healthy adults underwent a 1-hour vocal loading procedure, followed by randomization to a SS condition, vocal rest condition, or RV exercise condition. Treatments were monitored in clinic for 4 hours and continued extraclinically until the next morning. At baseline (BL), immediately after loading, after the 4-hour in-clinic treatment, and 24 hours post-BL, secretions were suctioned from the vocal folds bilaterally and submitted to enzyme-linked immunosorbent assay to estimate concentrations of key markers of tissue injury and inflammation: interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha, matrix metalloproteinase (MMP)-8, and IL-10. RESULTS: Complete data sets were obtained for three markers--IL-1beta, IL-6, and MMP-8--for one subject in each treatment condition. For these markers, results were poorest at 24-hour follow-up in the SS condition, sharply improved in the voice rest condition, and was the best in the RV condition. Average results for all markers and responsive subjects with normal BL mediator concentrations revealed an almost identical pattern. CONCLUSIONS: Some forms of tissue mobilization may be useful to attenuate acute vocal fold inflammation.

OBJECTIVES/HYPOTHESIS: To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis in order to ultimately develop both treatment and prevention paradigms. DESIGN: Translational study using archived human and fresh murine irradiated vocal fold tissue. METHODS: 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis was identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray, as well as real-time transcriptional analyses, were performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. RESULTS: Human irradiated vocal folds demonstrated increased collagen transcription, with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production, and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-beta increased in the lamina propria. CONCLUSION: Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability occurring in patients following laryngeal irradiation. The irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis.

Improving spectral resolution in cochlear implants is key to improving performance in difficult listening conditions (e.g. speech in noise, music, etc.). Current focusing might reduce channel interaction, thereby increasing spectral resolution. Previous studies have shown that combining current steering and current focusing reduces spread of excitation and improves virtual channel discrimination in a single-channel context. It is unclear whether the single-channel benefits from current focusing extend to a multi-channel context, in which the physical and perceptual interference of multiple stimulated channels might overwhelm the benefits of improved spectral resolution. In this study, signal discrimination was measured with and without current focusing, in the presence of competing stimuli on nearby electrodes. Results showed that signal discrimination was consistently better with current focusing than without, regardless of the amplitude of the competing stimuli. Therefore, combining current steering and current focusing may provide more effective spectral cues than are currently available.

This study investigated the integration of place- and temporal-pitch cues in pitch contour identification (PCI), in which cochlear implant (CI) users were asked to judge the overall pitch-change direction of stimuli. Falling and rising pitch contours were created either by continuously steering current between adjacent electrodes (place pitch), by continuously changing amplitude modulation (AM) frequency (temporal pitch), or both. The percentage of rising responses was recorded as a function of current steering or AM frequency change, with single or combined pitch cues. A significant correlation was found between subjects' sensitivity to current steering and AM frequency change. The integration of place- and temporal-pitch cues was most effective when the two cues were similarly discriminable in isolation. Adding the other (place or temporal) pitch cues shifted the temporal- or place-pitch psychometric functions horizontally without changing the slopes. PCI was significantly better with consistent place- and temporal-pitch cues than with inconsistent cues. PCI with single cues and integration of pitch cues were similar on different electrodes. The results suggest that CI users effectively integrate place- and temporal-pitch cues in relative pitch perception tasks. Current steering and AM frequency change should be coordinated to better transmit dynamic pitch information to CI users.

Cochlear implant performance in difficult listening situations is limited by channel interactions. It is known that partial tripolar (PTP) stimulation reduces the spread of excitation (SOE). However, the greater the degree of current focusing, the greater the absolute current required to maintain a fixed loudness. As current increases, so does SOE. In experiment 1, the SOE for equally loud stimuli with different degrees of current focusing is measured via a forward-masking procedure. Results suggest that at a fixed loudness, some but not all patients have a reduced SOE with PTP stimulation. Therefore, it seems likely that a PTP speech processing strategy could improve spectral resolution for only those patients with a reduced SOE. In experiment 2, the ability to discriminate different levels of current focusing was measured. In experiment 3, patients subjectively scaled verbal descriptors of stimuli of various levels of current focusing. Both discrimination and scaling of verbal descriptors correlated well with SOE reduction, suggesting that either technique have the potential to be used clinically to quickly predict which patients would receive benefit from a current focusing strategy.