DOSIMETRIC AND EARLY CLINICAL OUTCOMES OF THYROID-SPARING VOLUMETRIC MODULATED ARC RADIOTHERAPY IN LOCALLY ADVANCED HEAD AND NECK CANCERS.

Introduction: Radiation-induced hypothyroidism is a well-recognized entity that occurs after an interval of 15-21 months. However, in the treatment of locally advanced Head and neck Squamous cell carcinoma (HNSCC), thyroid-sparing techniques are infrequently employed. Aims: To evaluate the dosimetric and early clinical outcomes of thyroid-sparing SIB-VMAT technique (Simultaneous Integrated Boost - Volumetric Modulated Arc Radiotherapy) in patients of locally advanced HNSCC. Methods: In this two-arm prospective pilot study, patients in the study group received radiotherapy by SIB-VMAT technique with a thyroid constraint to a dose of 70 Gy to the gross disease and 59.4 Gy to nodal and subclinical disease in 33 fractions over 6 ½ weeks with concurrent cisplatin. V50Gy<75% was the thyroid constraint used. The control group was treated with the same dose and technique but without using a thyroid gland constraint. The dose-volume parameters of the thyroid gland, PTV (Planning Target Volume) along with thyroid profile were analyzed. Results: Twenty-six patients were recruited. Thyroid V50Gy of the study group (65.33 ±6.63 %) was significantly lower than that of control group (80.35 ±13.40 %) (p=0.003). Tumor dose parameters of both groups were compared and revealed no significant difference. At 18 months follow-up, the incidence of any degree of hypothyroidism was 46.15% in the study group and 23.07% in the control group (p=0.216). Conclusion: In locally advanced HNSCC, it is feasible to spare the thyroid gland without compromising the tumour coverage. This has the potential to reduce the frequency of radiation-induced hypothyroidism.

Investigation of high-frequency hearing loss and outer hair cell function of the cochlea in patients with psoriasis: a case-control study.

The inner ear can be the target of autoimmune attacks, and sensorineural hearing loss can occur as a complication in various non-organ-specific autoimmune diseases. The aim of this study was to compare cochlear functions and hearing evaluation in patients with psoriasis and controls. In total, 29 patients with psoriasis and 30 healthy controls (HCs) were included in the study. Pure-tone audiometry at 250, 500, 1000, 2000, 4000, 8000, 10 000, 12 000, 14 000 and 16 000 Hz was performed for patients as HCs, as were immittance measures including tympanometry, acoustic reflex and otoacoustic emission testing. There were statistically significant (P < 0.05) differences between patients and HCs for pure-tone thresholds at high frequencies, and for distortion product otoacoustic emission (DPOAE) responses and signal : noise ratio at all frequencies. In our study, based on DPOAE and audiological findings, there was damage to the outer hair cells of the cochlea, resulting in high-frequency hearing loss in patients with psoriasis.

Role of non-coding RNAs in head and neck squamous cell carcinoma: A narrative review.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with high recurrence, metastasis, and poor treatment outcome. Recent studies have reported that non-coding RNA (ncRNA) might play critical role in regulating different types of cancer. MicroRNAs (miRs) are short ncRNAs (20-25 nucleotides) responsible for post-transcriptional regulation of gene expression and may have a role in oncogenesis by acting as oncomiRs or tumor suppressor miRs. Long non-coding RNAs (lncRNAs) are heterogenous group of ncRNAs more than 200 nucleotides long, can act in cis and/or in trans, and have been also implicated in carcinogenesis. These molecules have been suggested to be promising candidates as diagnostic and prognostic biomarkers and for development of novel therapeutic approaches. In this review, we have summarized recent findings on role of these ncRNAs in HPV-negative (HPV-ve) and HPV-positive (HPV+ve) HNSCC. The available literature supports differential expression of both microRNAs and long non-coding RNAs, which include oncogenic ncRNAs (miR-21, miR-31, miR-155, miR-211, HOTAIR, and MALAT1) and tumor suppressor ncRNAs (let7d, miR-17, miR-375, miR-139, and MEG3) in HPV+ve HNSCC tumors as compared to HPV-ve tumors and they have distinct role in the pathophysiology of these two types of HNSCCs.

Detection of active human papilloma virus-16 in head and neck cancers of Asian North Indian patients.

BACKGROUND: Head and neck cancers (HNC) are one of the most common cancers in India. Human papillomavirus (HPV) has been identified as an emerging risk factor for HNC. METHODS: The present study was carried out to determine the active form of HPV-16 using a combination of PCR, viral load determination, HPV-16 E7 mRNA expression, p16, p53, and pRB immuno-histochemistry (IHC). RESULTS: A total of 226 HNC patients were enrolled in the present study. Sixty-seven (29.7%) of HNC cases were found to be HPV DNA positive. Thirty-two (14%) cases were HPV-16 DNA positive and 20 (9%) cases expressed HPV-16 E7 mRNA. HPV-16 mRNA/p16 positive cases had significantly increased viral load and integrated HPV-16 DNA. In summary, of total HNC patients, 6% cases were positive for both HPV-16 DNA and p16, and 5% were positive for both E7 mRNA and p16 IHC. We observed similar HPV-16 DNA/E7mRNA prevalence in oropharynx and oral cavity sites, however, oropharynx SCC had significantly higher viral load. CONCLUSION: Our results show low prevalence of active HPV-16 in North Indian HNC patients. HPV-16 E7 mRNA expression correlated with p16 nuclear positivity and increased viral load. Therefore, E7 mRNA expression may be used as a good surrogate indicator for active form of HPV-16 infection.

Predominance of PR3 specific immune response and skewed TH17 vs. T-regulatory milieu in active granulomatosis with polyangiitis.

OBJECTIVE: We compared levels of Th1/Th2/Th17 cytokines and T-regulatory cells in active and remitting granulomatosis with polyangiitis (GPA). METHODOLOGY: Twenty-one cases of GPA in active state as well as in remitting state and 20 healthy controls (HC) were enrolled in the study. Cytokines were detected in culture supernatants of PBMCs after stimulation with proteinase-3 (PR3) and phytohemagglutinin antigen (PHA). Serum IL-17 cytokine was studied by ELISA. T-regulatory cells (Tregs) were analyzed by flow cytometry. Gene expression of FOXP3 and ROR-γt was compared by Real Time PCR. RESULTS: We observed significantly increased level of IL-17 in serum as well in culture supernatants of PBMCs after PR3 stimulation along with ROR-γt gene expression in active disease state of GPA as compared to HC. Importantly, remitting state showed low levels of serum IL-17 with decreased ROR-γt gene expression and increased FOXP3 expression. Using PR3 as an immunostimulant, we could demonstrate the generation of IL-17 and TNF-α secreting effector memory cells during remission. Reduced FOXP3 expression with reduced IL-10 levels in active disease indicated the reduced function of Tregs in active disease. CONCLUSION: We observed Th17 dominant environment in peripheral blood of patients in active state of disease, with "hyporesponsiveness", in, in vitro stimulated PBMC-in their ability to secrete TNF-α and IL-6. Treg numbers were unaltered but function was compromised. Targeting PR3 specific effector memory cells, to prevent relapse, and instituting anti IL-17 therapy, or modulating Tregs could be newer forms of therapy for this serious autoimmune disease.

Role of autophagy in head and neck cancer and therapeutic resistance.

Head and neck squamous cell carcinomas (HNSCC) are one of the most common cancers worldwide, accounting for almost 50% of all malignancies in developing nations. Autophagy is a catabolic process involving turnover of long-lived proteins and organelles and is an important mechanism for cell survival under stress conditions. Autophagy has been shown to play a pivotal role in etio-pathogenesis of several cancers. Autophagy and apoptosis may be triggered by common upstream signals, and sometimes this results in combined autophagy and apoptosis, or defective apoptosis rendering immortalized epithelial cells highly tumorigenic. Autophagy has been found to buffer metabolic stress and may help in cell survival; however, inhibiting autophagy under conditions of nutrient limitation can restore cell death to apoptosis-refractory tumors. Therefore, autophagy acts as a double-edged sword in cancer therapeutics. Role of autophagy in pathophysiology and as a potential cancer therapeutics is a subject of intensive research. This review will focus on the role of autophagy and how it contributes to the pathogenesis and overcoming therapeutic resistance in HNSCC.

Early evaluation of voice quality in glottic cancer (T1, T2) following curative radiotherapy.

BACKGROUND: This is prospective study analyzing the subjective and objective quality of voice and voice related quality of life in patients of early glottic cancer (T1, T2 disease) before and after receiving curative radiotherapy. METHODS: Fifteen patients of early glottic carcinoma (T1, T2) underwent voice assessment using multidimensional voice protocol based on recommendation by European Laryngological Society which included Perceptual analysis of voice by speech therapist and otolaryngologist, acoustic analysis; aerodynamic efficiency analysis-Maximum phonation time; patient's self perception of voice analysis--Voice handicap index; and videolaryngostroboscopy. Assessment was done prior to commencement of radiation therapy and at 1 month and 3 months following radio- therapy. RESULTS: There was significant improvement in majority of the voice parameters post radiotherapy. Perceptual analysis showed significant improvement in GRBAS score following radiotherapy. Perturbation measures (jitter, shimmer, SNR, HNR) showed improvement post radiotherapy though remained inferior compared to controls. Mean fundamental frequency (Mean F0) and habitual frequency (habitual F0) decreased post radiotherapy. Intensity of voice increased following radiotherapy which was statistically significant (p < 0.05). There was significant improvement in the patient's perception of their quality of voice and voice related quality of life post radiotherapy. Maximum phonation time showed statistically significant improvement post-radiotherapy. Perceptual analysis of voice by professional observer correlated well with patients self perception of his own voice. CONCLUSION: Voice quality improves following radiotherapy but not all the patients regain normal voice. Improvement in voice quality improves quality of life of patients shown by improved voice handicap index.

Pyriform sinus injury in thyroidectomy: the unknown complicating the known.

Thyroidectomy is a common procedural skill in the armamentarium of an otolaryngologist but has its own set of complications. The more common complications are hypocalcaemia, recurrent laryngeal nerve palsy, injury to the external branch of the superior laryngeal nerve, postoperative bleeding, wound infection and, rarely, thyroid storm. High pyriform sinus injury during hemithyroidectomy is extremely rare, with this report being only the second reported case in the literature. A 61-year-old man presented with complaints of right-sided neck swelling. The patient had a 10cm × 8cm sized swelling in the anterior neck on examination. A contrast-enhanced computed tomography scan revealed a heterogeneously enhancing mass lesion involving the right lobe of the thyroid and isthmus with multiple nodules. The patient underwent right hemithyroidectomy with no intraoperative complications. The histopathology report describes a papillary thyroid carcinoma (cT3 N0 M0) with the presence of angioinvasion. On the fifth postoperative day, the patient complained of neck pain, suture site swelling and a change of voice. A volume of 50ml of whitish purulent fluid was evacuated. A laryngeal exam revealed restriction in mobility of the right vocal cord. The oesophagogram revealed the iatrogenic injury to the hypopharynx. The oesophageal leak gradually resolved after 6 weeks, as evidenced by multiple contrast oesophagogram, without any need for surgical intervention. We theorise that, while operating on long-standing monster thyroids, extra care should be given while dissecting in the tracheoesophageal groove as the stretched mucosa, an extracapsular extension of disease and lymphovascular invasion can all jeopardise the underlying structures.

Hypermethylation of carcinogen metabolism genes, CYP1A1, CYP2A13 and GSTM1 genes in head and neck cancer.

OBJECTIVES: To investigate the role of aberrant hypermethylation of carcinogen metabolism pathway genes, CYP1A1, CYP2A13 and GSTM1 in head and neck cancer independently as well as its relation to tobacco and alcohol consumption and CYP1A1 and CYP2A13 polymorphisms in Indian population. METHODS: Seventy-three histologically confirmed head and neck cancer patients undergoing treatment in Postgraduate Institute of Medical Education and Research, Chandigarh, India were recruited. Non-cancerous tissues were obtained from 19 trauma subjects undergoing maxillofacial surgery. Methylation-specific PCR was performed to determine the methylation status of selected genes. RESULTS: The aberrant hypermethylation of CYP1A1, CYP2A13 and GSTM1 genes was found in cancer tissues with frequency of about 39.7%, 27.4%, and 58.1%, respectively, and in normal healthy tissues with a frequency of about 10.5%, 15.8%, and 20.0%, respectively. Hypermethylation of CYP1A1 (P 0.027) and GSTM1 (P 0.010) showed significant association with head and neck cancer. We also observed significant interaction between smoking and methylation status of CYP1A1 (P 0.029) and CYP2A13 (P -0.034) in head and neck cancer. No association was observed between methylation status and alcohol consumption, clinical features and genetic polymorphisms of CYP1A1 and CYP2A13. CONCLUSIONS: Hypermethylation of carcinogen metabolism pathway genes independently and in interaction with smoking is associated with increased risk of head and neck cancer.

Normalisation of voice parameters in patients with unilateral vocal fold palsy: is it realistic?

BACKGROUND: Disorders of voice can limit an individual's participation and impair social interaction, thus affecting overall quality of life. Perceptual and objective evaluations can provide the clinician with detailed information regarding voice disorders. METHODS: This study comprised 40 subjects aged 34-46 years, 20 of whom (10 male, 10 female) had unilateral vocal fold palsy. Data were obtained for all participants from: the Voice Handicap Index, the grade, roughness, breathiness, asthenia and strain ('GRBAS') scale, acoustic voice analysis, electroglottography, and voice range profiles. RESULTS: The voice evaluations revealed statistically significant (p < 0.05) differences between the controls and study group, both in males and females, pre- and post-therapy. CONCLUSION: Despite the normalisation of vocal parameters, acoustic, perceptual and self-rated assessments revealed statistically significant differences after therapy. Hence, acoustic measures, namely electroglottographic perturbation, and voice frequency and intensity range, are recommended prior to termination of therapy.

Comparative efficacy and safety of terfenadine with pseudoephedrine and terfenadine alone in allergic rhinitis.

A randomized, double-blind clinical trial was conducted on 41 adult patients to compare the efficacy and safety of the combination of terfenadine and pseudoephedrine with that of terfenadine alone. Efficacy of treatment evaluated by the physician and patients showed an excellent rating in 45.45% patients in the combination treatment group compared with an excellent rating in 10.53% in the single treatment group. The difference between both treatments was statistically significant, with a z value of 1.660 (p < 0.05). The combination of terfenadine and pseudoephedrine was found to result in faster relief in a greater number of patients than terfenadine alone. However, both drugs were well tolerated.

Incidence of pharyngeal hypophysis in neonates a histologic study.

The presence of adenohypophysial tissue in the nasopharynx is no longer disputed. This study was performed in 50 neonatal cadavers subjected to medical autopsy within 6 hours of death. The aim was to study the incidence of extrasellar pituitary tissue in the nasopharynx and its various histologic cell types. The transpalatal approach was used to obtain the specimens. The specimens were stained with hematoxylin and eosin and periodic acid-Schiff-orange G for selective demonstration of adenohypophysial cells. Histopathologic evaluation led to the detection of pituitary tissue in 16% of the examined specimens. Selective staining demonstrated a 6% positive incidence of adenohypophysial cells. The pharyngeal hypophysis exists in 2 forms: a typical adenohypophysial collection of cells and an atypical subepithelial cluster. The incidence of hypophysial tissue was higher in the older neonates, perhaps because of hormonal stimulation of the caudal remnant of Rathke's pouch.

Ultrasound versus physical examination in staging carcinoma of the mobile tongue.

Surgical therapy for early lesions of the tongue should have the potential to be both oncologically sound and easy to rehabilitate. Obviously, the amount of tongue left behind after surgery is proportional to the post-operative function. Hence accurate mapping of the diseased tongue is of paramount importance in order to limit or extend the resection margins. We have evaluated the use of ultrasound in carcinoma of the tongue, and also compared its relative accuracy with physical examination for determining the extent of growth, keeping the histopathological size as a gold standard. We found that ultrasound is more accurate in detecting T2 and T3 tumours than T1 lesions. Intraoral sonographic mapping may be the answer for such small lesions. In addition, ultrasonography is beneficial in showing spread to contiguous areas of the tongue. However, post-radiation fibrosis and frank residual disease were not differentiated accurately by ultrasound. Thus ultrasonography can be an effective investigative tool and together with physical examination it can increase diagnostic accuracy leading to precise surgery for carcinoma of the tongue.

Fibreoptic assessment of post intubation laryngotracheal injuries.

The use of endotracheal intubation for respiratory support of critically ill patients has become a standard life saving form of therapy. Most complications of intubation become apparent only after extubation which may manifest in the early or late post extubation period. This study was undertaken to demonstrate the occurrence and extent of laryngotracheal injuries in intubated patients by performing flexible fibreoptic bronchoscopy at varying intervals following extubation. It was found that initial laryngoscopy findings were more pronounced in patients intubated for upto twelve days. Furthermore, it was also observed that the initial laryngeal pathology seen on fibreoptic laryngoscopy was not an accurate predictor for the development of adverse post extubation sequelae. Maxillary sinusitis developed significantly in patients intubated nasally. Routine flexible fibreoptic examination of the larynx following extubation is recommended for early detection of granulomas, synechia of vocal cords and vocal cord immobility to prevent troublesome sequelae.

Post laryngectomy complications and their mode of management--an analysis of 203 cases.

Two hundred and three laryngectomized patients have been evaluated for the possible causes of post operative complications. 58 out of 203 patients (28.5%) developed pharyngocutaneous fistula. Wound infection was present in 57 cases (28%). Two patients had flap necrosis and 12 patients developed dysphagia after surgery due to pharyngeal stenosis. The possible causes attributed to high occurrence of pharyngocutaneous fistula are, advanced nature of disease, preoperative radio therapy and wound sepsis. Prior to 1980, the incidence of pharyngocutaneous fistula in our series (Arora et al. 1983) was 41.6 percent. But it decreased to 13.7 percent between January 1981 to June 1987. The important factors which led to the decreased incidence of pharyngocutaneous fistula were thought to be the change of suture material for pharyngeal repair from chromic catgut to Vicryl, use of vacuum suction as a replacement of corrugated rubber drain and aseptic syringe drainage and postoperative coverage with broad spectrum antibiotics.

Localized amyloidosis of the nasopharynx.

A case of localized amyloidosis of the nasopharynx is presented. This is only the seventh case report of nasopharyngeal amyloidosis to the best of our knowledge. Though rare, this disease should be diagnosed early and properly treated with surgery. All patients of localized disease should be followed up for any evidence of systemic amyloidosis.

Post traumatic facial paralysis--a review.

A retrospective analysis of 23 cases of post-traumatic facial nerve injury has been done. Majority of the cases had a conductive or a mixed deafness. The Schirmer's test has been considered to be one of the main indicators to determine the site of injury. The mastoid segment of the facial nerve was found to be injured in 52% of the patients. The surgical approach in patients with post-traumatic facial nerve paralysis should be transmastoid. This can be combined with a middle fossa approach in patients with a positive Schirmer's test.

Comparison of auditory electrophysiological responses in normal-hearing patients with and without tinnitus.

INTRODUCTION: Tinnitus is a disturbing symptom and is often the main reason for otology referral. It is usually associated with hearing loss of varying aetiology, and is thought to begin in the cochlea, with later abnormal central activity. We hypothesise that tinnitus without hearing loss may be caused by central and subcortical abnormalities and altered outer hair cell function. AIM: To compare the auditory brainstem responses, middle latency responses and otoacoustic emissions in normal-hearing individuals with and without tinnitus. METHODOLOGY: The audiological test results of 25 normal hearing subjects with tinnitus (age 18-45 years) were determined, and compared with those of a control group. RESULTS: A statistically significant difference was found between study group tinnitus ears vs control group ears, as regards wave I latency prolongation, shortening of wave V and absolute I-III and I-V interpeak latency, enlargement of wave Na and Pa amplitude, and distortion product and transient evoked otoacoustic emission signal-to-noise ratios. There was no statistically significant difference between unilateral vs bilateral tinnitus ears. CONCLUSION: The pathogenesis and optimum management of tinnitus are still unclear. It often occurs with primary ear disease, usually associated with hearing loss, but may occur in patients with normal hearing. Observed changes in auditory brainstem and middle latency responses indicate central auditory alterations. Tinnitus involves both peripheral and central activity, and complete audiological and neurophysiological investigation is required. Management should be based on both audiological and neurophysiological findings.

Desferioximine induced Ototoxicity in Thalassemic patients.

BACKGROUND: Thalassemia is a hereditary disorder requiring regular blood transfusion. PURPOSE: To determine hearing sensitivity in transfusion-dependent thalassemics who were receiving desferioximine and on oral iron chelation (desferioximine) therapy. METHODS: 26 patients with B-thelassemia in the age range of 5-22 years were enrolled in the thalassemia transfusion unit in the Advanced Pediatric Center of Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. The patients to be enrolled in this study were randomly selected. RESULTS: It was observed that the hearing deteriorated in patients who were given injected desferioximine whereas it fell within normal limits in case of those who were given oral iron chelation therapy. CONCLUSON: This study confirms the necessity of regular audiological monitoring during the course of the disease.