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.

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.

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.

Paranasal sinus aspergillosis: its categorization to develop a treatment protocol.

A prospective study was conducted in 25 consecutive patients of paranasal sinus aspergillosis to categorize and treat them based on a fixed treatment protocol. The three types of aspergillosis categorized as per definitive criteria were chronic invasive (six), non-invasive (fungus ball) (seven) and non-invasive destructive (12). Adjuvant chemotherapy was employed in non-invasive destructive and chronic invasive disease. Ketoconazole was used in the first variety and itroconazole in the latter. Only two patients had recurrence after a mean follow-up of 11 months (range: 6-20 months). They belonged to the non-invasive destructive category and the recurrence had progressed to invasive variety. It is suggested that non-invasive destructive disease should be followed up regularly with endoscopic examination, CT and fungal serology to detect recurrence. Categorization of the paranasal sinus aspergillosis helps to institute proper treatment. Adjuvant chemotherapy in the form of ketoconazole along with surgery is effective in non-invasive destructive disease to prevent recurrence and progression to invasive disease. Chronic invasive disease with its propensity to involve orbit and intracranial cavity should be managed at the earliest with surgery and itraconazole.

High flow vascular malformations : Review of literature and a case report.

Vscular malformations are uncommon vascular lama. Low flow malformations hatve always been confused with kaemangiamas. Arteriovenous malformations (AVMs) arc extremely rure. We present a cue of massive AVM of the head and neck region and. disiusstke dlfflculties of cmbotisatim and surgical management in such cases. The relevant literature has also been reviewed.

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.

Evaluation of vestibular functions in otosclerosis before and after small fenestra stapedotomy.

Vestibular functions in twenty-five patients with otosclerosis were analyzed before and after undergoing stapes surgery. Vertigo was present preoperatively in 6 patients, which disappeared completely after 4-6 weeks of surgery in all the patients indicating the usefulness of stapedectomy. Patients with otosclerosis demonstrated hypoexcitability compared to controls, which was statistically significant for right cold and hot irrigation. Our results showed equal culoric abnormalities in patients with mixed hearing loss and conductive loss. Patients with obliterative focus at surgery had impaired vestibular functions compared to non-obliterative foci without any statistical significance. A longer piston used at surgery tends to produce more vestibular damage compared to a smaller piston. Finally, the degree of vestibular dysfunction seems to be inversely proportional to the hearing result.

Mediastinitis following deep neck infections : A therapeutic challenge.

OBJECTIVE: To emphasize the salient features of surgical management of Mediastinitis occurring secondary to deep neck infections. STUDY DESIGN: Case series. Retrospective analysis SETTING: Institutional teaching department Patients Four consecutive cases of mediastinal abscess treated between 1990 to 1996. Selection criteria were presence of deep neck infection radiological evidence of widening of mediastinum and confirmation of mediastinal infection at surgery. Computerized tomography of neck and thorax was done in one case to document the extent of abscess. SARGICAL MANAGEMENT: All the patients underwent transcervical drainage of neck abscess and superior mediastintomy. The involved spaces in the neck and mediastinum were irrigated with betadine antimicrobial solution and negative suction drains put in the superior mediastinum ta facilitate contituous drainage of the mediastinum. One patient required intercostal chest drainage for associated empyema. Tracheotomy was done in all the patients. RESULTS: All the patients survived and discharged after a hospital stay of around three weeks. CONCLUSIONS: Mediastinal complication of deep neck infections can he alarmingly rapid and can be effectively managed by early recognition and aggressive surgical drainage combined with antibiotic therapy after appropriate aerobic and anaerobic cultures.

Aural cholesteatoma: role of tumor necrosis factor-alpha in bone destruction.

HYPOTHESIS: The bone destruction in cholesteatoma is multifactorial. This study was undertaken to define the role of tumor necrosis factor-alpha (TNF-alpha) in bone destruction associated with cholesteatoma. BACKGROUND: Tumor necrosis factor-alpha is an important inflammatory cytokine secreted by activated macrophages. It stimulates keratinocytes as an autocrine growth regulator. Few authors have localized TNF-alpha in aural cholesteatoma. An attempt was made in this study to show a correlation between TNF-alpha and cholesteatoma associated bone destruction by localizing TNF-alpha in cholesteatoma and measuring its serum level. METHODS: Serum TNF-alpha levels were measured in 20 patients with cholesteatoma of temporal bone and histochemical staining was used to localize TNF-alpha in pathologic tissue excised at surgery. RESULTS: Serum TNF-alpha levels in patients with cholesteatoma were significantly higher than in controls. In addition, TNF-alpha levels in patients with bone destruction were higher than in those without bone destruction. However, there was no correlation between age of the patient and serum TNF-alpha levels. The TNF-alpha was localized in various layers of cholesteatoma epithelium using indirect immunoperoxidase staining. CONCLUSION: TNF-alpha is one of the cytokines produced by cholesteatoma that may be an important mediator of bone destruction associated with cholesteatoma. TNF-alpha has been localized in various layers of cholesteatoma and exerts a locally destructive effect on bone. Serum TNF-alpha levels are related to the extent of bone destruction.

Mastoid pneumatization and otosderosis-is there a correlation.

The environment versus the genetic influence on the size of the mastoid pneumatization has been debated for years. A concrete evidence of the influence of environmental factors (e.g. inflammation) or heredity on pneumatization is still lacking. In this study the extent to mastoid peumatization in thirty otosclerotic ears was compared with control ears. The size of mastoid pneumatization was measured by the use of Law lateral x-ray projection with the help of planimetry. It was found that the average pneumatized area in otosclerotic ears was 14.73+ -3.55 cm2 compared to 10.60+3.62 cm2 in control ears which was statistically significant. In addition the mean area of mastoid air system was found to be more in the operated ears compared to the contralateral ears, the difference being statistically significant. However there was no correlation of mastoid pneumatization with degree and duration of hearing loss and type of otosclerotic focus. Our findings therefore show a link between otosclerosis and highly pneumatized mastoids thus indicating a likelihood of heredity playing a role in determining final type ot pneumatization.

Paranasal sinus mycoses in north India.

Recognizing the high incidence of paranasal sinus mycoses in north India, we analysed retrospectively the clinical, mycological and management aspects of 178 patients with proven disease attending our institute. On the basis of clinical, radiological, histopathological and mycological findings, the patients could be categorized into those with allergic (8), non-invasive (92) and invasive (78) disease types. Bony erosion without mucosal invasion by fungi was seen in 16 patients with non-invasive disease. Young men from rural areas were the most commonly affected. Rhinorrhoea with nasal polyposis (45.8%) and proptosis (46.4%) was the most common presentation. Concurrent involvement of the maxillary and ethmoid sinuses was common in these patients, whereas isolated sphenoid and frontal sinuses were involved in the invasive variety only. Orbital and intracranial extensions were detected in 100% and 13.2%, respectively, of patients with the invasive type of disease. Aspergillus flavus (79.7%) was the most common isolate. Surgical debridement and sinus ventilation were adequate for the effective management of the non-invasive disease. However, adjuvant medical therapy was included in treatment of the semi-invasive and invasive varieties of the disease. Itraconazole was found to be most useful in prevention of recurrence in the invasive type. Mortality was highest (33.3%) among patients with zygomycotic infection. Invasive fungal granuloma with orbital and intra-cranial invasion is a distinct entity in terms of its clinical course and treatment compared with non-invasive fungal sinusitis, and it needs to be treated aggressively with surgical excision and postoperative itraconazole.

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.

Malignant fibrous histiocytoma of maxilla - a report of five cases and review of literature.

Malignant fibrous histiocytoma of the maxilla is a rare malignant tumor of the bone. Affection of maxilla does not occur very commonly. In this report five cases of fibrous histiocytoma have been presented along with a review of literature.