Detection of interleukins-6 and 8 in saliva as potential biomarkers of oral pre-malignant lesion and oral carcinoma: a breakthrough in salivary diagnostics in Pakistan

Oral cancer is at rise in our population due to increasing use of areca nut [Betel nut] with or without tobacco. It is the second frequent malignant tumour for both the gender in Pakistan. This non-interventional case control study was carried out with the aim to explore saliva as diagnostic medium for detecting interleukins [IL] 6 and 8 as biomarkers of pre-malignant lesions [PML] and oral carcinoma. Total 105 subjects were recruited and were divided into three groups "A", "B" and "C" each comprising of 35 subjects. Group "A" comprised of cases with strong clinical evidence of oral PML. Group "B" constitute clinical and histologically proven OSCC and group "C" include disease free subjects as controls. Saliva from all the recruited subjects was procured by drooling method and stored at-20[degree sign]C before further process. All the collected samples were centrifuged at 4500 rpm for 15 minutes at 4[degree sign]C. Supernatant fluid was used in ELISA for detection and quantification of IL-6 and IL-8. Data was analysed by using Chi-square test and multivariate analysis was done by non-parametric test. P-value of 0.05 was taken as standard reference. Significant co-relation was found for qualitative salivary detection of IL-6 and IL-8 among the groups [P<0.001 and <0.0001 respectively]. Regarding quantitative salivary concentration of leukotrienes, no significant co-relation was found in levels of IL-6 among the groups while there was significant association of IL-8 levels between the groups [P<0.0001].On post Hoc multiple comparison, significant co-relation was found among oral PML group and controls [P=0.001] and OSCC group and control [P=<0.0001]. In conclusion salivary detection of IL-6 and IL-8 could be used as probable biomarker for early detection of oral PML and OSCC in etiologically distinct population of Pakistan

Salivary detection of human Papilloma virus 16 and 18 in pre-malignant and malignant lesions of oral cavity: Is it feasible in Pakistani context of Socio-Cultural Taboos?

To evaluate salivary detection of HPV-16 and 18 would be feasible and informative biomarker for oral pre-malignant and malignant lesion in our population. This non-interventional, case control study was carried out at department of E.N.T, Head and Neck Surgery, Dow University of Health Sciences, Dow Medical College and Civil Hospital Karachi, Pakistan between July 2011 to December 2012. Total of 105 cases were recruited. These were divided in three groups 'A', 'B' and 'C having 35 subjects each. Group'A' constitutes patients having strong clinical evidence of oral pre-malignant lesions [PML]. Group 'B' includes historically proven oral squamous cell carcinoma [OSCC] and Group 'C' comprised disease free subjects as controls. After taking informed consent, relevant clinical history was recorded on institutional approved performa. Saliva from all subjects was procured by standard 'drooling method'. Samples were stored at +4°C and later transferred to Laboratory to store at-20°C before further process. Samples werKfcentrifuged at 4500 rpm for 15 minutes at 4°C. Cell pellets sediments were used for identification of HPV-16 and 18 by real-time PCR method. Data was entered and analysed using SPSS version 16. P-value of 0.05 was taken as standard. In group 'A', HPV-16 was detected in 3 [8.6%] cases while HPV-18 was not detected in any of the subject. In group 'B', HPV-16 was detected in 07 [20%] while HPV-18 was found in 06 [17.1%] cases. Mixed HPV-16 and HPV-18 were found in 02 [5.7%] cases. In group 'C, HPV-16 was detected in 03 [8.6%] while HPV-18 was not detected in any of the subjects. Significant relationship was observed between the groups for HPV-18 detection [P= 0.002] while for HPV-16, no significant association was found [P= 0.245]. HPV infection for the causation of oral cancer cannot be fully established possibly due to small sample size. More over differences in genetic makeup, environment, indulgence in peculiar risk factor habits, sexual practices and difficult evaluation of the acquisition of viral load due to socio-cultural and religious restrictions could be the reason

Molecular diagnosis of oral pre-malignant lesions and oral squamous cell carcinoma in saliva-a breakthrough in Pakistan

To evaluate salivary detection of interleukin 6 and 8 and high risk HPV-16 and 18 are informative biomarkers of Oral Pre-malignant Lesion [PML] and Oral Squamous Cell Carcinoma [OSCC] in our population. July 2011 to December 2012. Total 105 cases were included. The subjects were divided in three groups 'A', 'B' and 'C' having 35 participants each. Group 'A' comprised of patients having strong clinical evidence of oral PML. Group 'B' constitutes histologically proven OSCC and Group 'C' includes disease free subjects as controls. Relevant clinical history was recorded after informed consent on institutional approved performa. Saliva was collected as per standard drooling method'. Samples were stored at +4oC and later transferred to Dow Diagnostic, Research and Reference Laboratory to store it at -20oC before further process. Samples were subjected to centrifugation at 4500 rpm for 15 minutes at 4oC. Supernatant fluid phase was used in ELISA for detection and quantification of IL6 and IL8. . Cell pellets were used for identification of high risk HPV-16 and 18 by real-time PCR. Data was entered and analyzed on SPSS version 16. P-value of 0.05 was taken as standard reference. In group 'A', IL6 was not detected in almost all the subjects except one case. IL8 was detected in 26/35 [74.3%] subjects and not detected in 09 [25.7%] cases. In group 'B', IL6 was detected in 13 [37.1%] cases and in 22 [62.9%] cases, it cannot be detected. IL8 was detected in 33 [94.3%] and it was not detected in 02 [5.7%] subjects. It is observed that IL8 is consistently found raised in group 'A' and 'B'. In group 'C', IL6 was not detected in any of the subject while IL8 was detected in 10[28.6%] cases. Significant association was found for qualitative salivary detection of IL6 and IL8 between the groups [P= < 0.0001 and < 0.0001 respectively]. Regarding quantitative salivary concentration of IL6 and IL8, no significant co-relation was found in salivary levels of IL6 between the groups while there was significant association of salivary IL8 levels between the groups [P= <0.0001]. On post Hoc multiple comparison, significant co-relation was found in IL8 levels between oral PML group and controls [P=0.001] and OSCC group and controls [P= <0.0001]. In group 'A', HPV-16 was detected in salivary samples of 3 [8.6%] cases while HPV-18 was not detected. In group 'B', HPV-16 was detected in the salivary samples of 07 [20%] cases while HPV-18 was detected in 06 [17.1%] cases. Mixed HPV-16 and HPV-18 were found in 02 [5.7%] cases. In group 'C', HPV-16 was detected in 03[8.6%] cases while HPV-18 was not detected in any of the subjects. Significant relationship was observed between the groups for salivary HPV-18 detection [P= 0.002] while for detection of HPV-16, no significant association was found [P= 0.245]. Salivary concentration of IL6 and IL8 in oral PML and oral cancer are useful biomarkers in our population. Detection of HPV infection for the causation of oral cancer cannot be fully established possibly due to small sample size. More over different genetic makeup, environmental and geographic differences, indulgence in peculiar risk factor habits and different sexual practices compared to west due to socio-cultural and religious restrictions could be the reason

Hepatitis 'B' and 'C' seropositive cases in the practice of ENT-head and neck surgery, where do we stand?

To determine the frequency of hepatitis 'B' and 'C' virus in patients admitted with pathologies of Ear, Nose, Throat or Head and Neck for surgery,: Non intervention, descriptive. Department of ENT-Head and Neck Surgery Dow University of Health Sciences and Civil Hospital Karachi, from September2006 to August 2008. Sampling was done by probability stratified technique. A total number of 832 patients admitted in department of ENT. Civil Hospital Karachi were screened by ELISA method before surgery. All the subject were unaware of their serological status regarding hepatitis B surface antigen [HBs Ag] and hepatitis C antibody [HCV Ab]. Patients admitted through emergency department, those admitted for conservative management and those under 10 years of age were not included in this study. Age, gender and risk factors like history of blood transfusion, dental treatment, any surgical intervention, home deliveries and shaving by barbers were taken as variables. Statistical analysis was done on SPSS, Out of 832 patients screened, 126 [15.14%] were seropositive out of whom 52 [41.26%] were males and 74 [58 73%] were females. HBV was positive in 31 [24.60%] [M=12; F=19] and HCV was positive in 95 [75. 39%] patients [M: 38, F: 57]. Variables did not show any statistically significant effect over the results. Universal screening rather than selective screening for HBV and HCV infection of all pre surgical cases should be exercised to prevent spread of infection among healthcare workers as well as community

Is lateral rhinotomy, an adequate surgical approach for juvenile naso-pharyngeal angiofibroma

The objective of the study was to determine optimal surgical approach in patients with JNA. Retrospective, descriptive. The study was carried out at the department of Ear, Nose, Throat, Head and Neck Surgery, Dow Medical College and Civil Hospital, Karachi from 1996-2007. All the young males who visited out patients department with the history of recurrent intractable epistaxis, nasal obstruction, proptosis, fullness and asymmetry of face and were diagnosed as a case of JNA on the basis of history, clinical examination and CT scan, were included in the study. All the diagnosed cases of recurrent JNA and other causes with similar symptoms were excluded. Almost all the included patients underwent digital subtraction angiography with embolization of main feeding vessel 24-48 hours before surgery. Chandler staging system was used to stage the disease. Lateral rhinotomy approach was employed in majority of the cases for exploration and removal of JNA. The out come were discussed for lateral rhinotomy as an optimal surgical approach in patients with JNA in term of ease of approach, complete removal and recurrence. Total of 53 cases of JNA were included in the study. All were young males between the age group from 8-22 years. Majority of the patients were between 13 to 18 years of age. No female patient was reported. Majority of the patients presented with triad of symptoms with recurrent epistaxis [n-53] nasal obstruction [n-53] and nasal mass [n-41]. Others presented with additional symptoms of nasal discharge [n-46], snoring [n-43] speech defect [n-32], headache [n-23], facial asymmetry [n-20], visual problems, like proptosis and diplopia [n-09] and impairment of hearing [n-19]. Diagnosis was made by clinical examination, C T scan and angiographic findings with embolization 24-48 hour prior to surgery [n-45]. Lateral rhinotomy approach for extirpation of the JNA was employed in 41 cases and Weber-Furguson approach in 07 patients. Midfacial degloving approach was used in 03 patients and in 02 cases transpalatal approach was employed where the extent of the lesion was limited to nasopharynx. Recurrence was found in 03 cases of JNA approached through lateral rhinotomy during 1-2 years follow-up. Lateral rhinotomy approach to nose and nasopharynx gives an adequate exposure in almost all the cases of JNA

Cochlear and vestibular toxicity by the use of ototoxic drugs - the regional experience

The objective of the study is to find out the common pharmacologic agents causing ototoxicity in our region with their pattern of presentation and effects on the inner ear. This study was conducted at department of Ear, Nose, Throat, Head and Neck Surgery, Civil Hospital Karachi, over a period of three years from January 1998 to December 2000. A total of 44 patients were included who presented at ENT department with the diagnosis of ototoxicity. The diagnosis was established in each case by taking detailed history, through ENT examination and related investigations. All these patients were followed up regularly for a maximum of six months. Out of44 patients, 32 were male and 12 were female patients with mean age of 42.2 years. Majority of the patients had some form of cochleotoxicity with symptoms of deafness in 95.4% and tinnitus in 36.6% of the cases. Vestibular toxicity with symptoms of vertigo and sense of imbalance were presented in 29.5% of the cases. 26 patients received only one ototoxic drug while 18 patients had received more than one ototoxic drug at one time. Gentamycin was the commonest offending agent for ototoxicity in 40.9% of the cases. In this study no patient of ototoxicity was found due to macrolide antibiotics, salicylates or any non-steroidal anti-inflammatory drugs. Sensori-neural hearing loss in majority of the patients was moderate to severe in nature

Endoscopic removal of bullet from orbital apex

Penetrating injuries of face are not uncommon. Bullets or pallets may be lodged anywhere in the cavities of skull as a result of firearm injury. Lodgment of a bullet within the orbit through nose is uncommon. An eighteen 18 years old married woman sustained a bullet injury, which entered through lateral wall of the nose and lodged at left orbital apex area. The bullet was removed endoscopically via left nostril without any damage to the eye or disturbance in vision

Histological spectrum of oral leukoplakia; a clinicopathological perspective

Histological analysis of clinically diagnosed cases of oral leukoplakia for assessment of malignant potential. Observational descriptive study. Biopsies of 113 cases of clinically established oral leukoplakia were assessed for clinical appearance and correlated with histology to determine the frequency of epithelial dysplasia and carcinoma, at Department of Pathology, Dow Medical College, Dr. Ehsanullah's laboratories Pvt. limited and Dr. Tahir laboratory, Taj Medical Complex, Hamdard University Hospital during the period of 2003-2006. The histological spectrum of 113 cases revealed hyperplastic epithelium predominantly in 85 [75.22%] cases. 14[12.38%] cases displayed mild to moderate dysplasia. Severe dysplasia I carcinoma in situ was noted in 5[4.4%] cases and microinvasive carcinoma was detected in 6[5.3%] cases. This study confirms that oral leukoplakia is a precancerous lesion and that certain clinicopathological characteristics indicate greater risk to warrant prompt biopsy examination and aggressive management

Plexiform neurofibroma of external auditory canal - a rare entity

We present a case of plexiform neurofibroma of external auditory canal [EAC] in a 43 years old male. Neurofibroma of EAC presents in rare cases. It is a benign tumor arising from the connective tissue of the nerve sheath, now thought to arise from schwann cells rather than fibroblasts. This tumor causes a fusiform enlargement of a nerve. This rare case is reported in a 43 years old male, who presented with pain in the left ear, found to have a polypoidal mass in [L] external auditory canal. Histological examination of the excised specimen revealed the features suggestive of plexiform neurofibroma of external auditory canal

Ceruminoma of external auditory canal: a rare entity

We present a case of polyp of External Auditory Canal [E.A.C.] in 26 years old male, which turned out to be a ceruminoma on histopathological examination. It is a rare entity arising from the ceruminous glands present in the skin o f outer cartilagineous part o f E.A. C. The most extensive review of the topic lists only 32 cases over a period of 30 years worldwide. Meticulous local medical literature search revealed that this is most likely the first case ever-reported in Pakistan. The wide local excision of the growth was done after Examination Under Microscope [E. U.M.] and tissue sent for histopathological examination, which was reported as 'Ceruminoma'. Tympanic membrane was found intact on E. U.M under general anaesthesia

Unusual pathology presented as neck lump

Neck lump is a common presentation in the outpatient clinics of otolaryngology, Head and Neck Surgery. It can be diagnosed on the basis of history, clinical examination, investigations and categorized according to the age of presentation. We present a case of young adult girl who had rightsided neck lump since four years. On the basis of fine needle aspiration cytology [F.N.A. C], she was diagnosed as a case of cervical chronic granulomatous inflammation consistent with tuberculosis. She was prescribed antituberculous treatment [A.T.T.] for 09 months but the swelling persists without any change. Excisional biopsy of the neck lump was performed and the histopathology revealed Histiocytoma Cutis, a variant of benign fibrous histiocytoma also called Fibrous Xanthoma or Xanthoma Cutis. Extensive English medical literature search on net revealed it to be a rare pathology which, to the best of our knowledge, has never been reported in locoregional literature and very rare over the globe

Deafness in highlanders.

Hearing impairment is a common health problem throughout the world. Over two million human beings on the earth are either deaf or hearing impaired, most of them in the developing countries. Pakistan is a land of multiethnic, multiracial, multilingual and varied anthropological cultures and populations. A substantial number of children and adults are suffering from hearing impairment, mostly provoked by poverty and lack of health facilities. This non-interventional descriptive study was carried out while providing primary ear care and conducting an epidemiological survey in the Northern territories of Baltistan, that covers a large terrain of Himalayan mountains of the Hindukush and Korakoram Range. A total of 1964 patients were examined during 7 camps conducted by IMPACT Pakistan in 1998, out of which 1160 were females and 804 were males. Short history was recorded and meticulous ear examination was performed, which includes otoscopy withpneumatic attachment and tuning fork testing. Tympanometry was performed in selected cases of glue ears having clinical evidence of effusion behind the drum. Common causes of deafness and hearing impairment were drawn from this study. Glue ear was found in 503 patients [25.61%] out of which 353 patients-were selected for tympanometry Impacted hard wax was found in 402 patients [20.46%]. Chronic suppurative otitis media [C.S.O.M] was found in 307 patients [15.61%] with discharging perforations in 178 patients [57.98%], dry perforations in 111 patients [36.15%] and cholesteatoma in 18 patients [5.86%]. Tympanosclerotic patches were found in 231 patients [11.76%]. Sensorineural hearing loss [SNHL] was found in 225 patients [11.43%], majority of them were due to aging process [presbaycusis] in 97 cases [43.11%]. Post-infectious neural loss was found in 55 cases [24.44%]. 39 cases [17.33%] of SNHL were associated with goitre and 7 cases [3.11%] of syndrome associated hearing loss were identified. The final message is that all the causes seen in mountainous areas of Northern territories, as indeed elsewhere in Pakistan are preventable. All we need is public awareness, which can be achieved through the help of the international agencies, particularly the W.H.O.

giant pleomorphic adenoma of parotid gland.

Pleomorphic adenoma is the most common benign neoplasm of parotid gland, generally presenting as slowly enlarging firm painless mass. The vast majority are 2-6 cm in size, when resected. We report a case of big water-melon sized parotid mass measuring 22 x 16 cm. It proved to be a pleomorphic adenoma. To the best of our efforts and literature search, this is the largest parotid mass ever resected in Pakistan. The mass was resected successfully without post-operative complications

Glue ear at the highlands of Himalayas

Otitis media with effusion [OME] is common clinical entity in children. Adult onset glue ear is not uncommon in our country. This study was carried out while providing primary ear care and conducting epidemiological survey in the northern territories of Baltistan in the Himalayan range of mountain terrain. Total of 503 subjects, having the strong clinical evidence of glue ear were included in the study during 07 ENT camps in 1998. 295 [58.64%] were males and 208 [41.35%] were females between the age range of 05 to 85 years. 364 [72.36%] cases were bilateral and 139 [27.63%] were unilateral. Tympanometry was performed in 353 selected subjects. Type B tympanograms were found in 296 [83.85%]. Type C in 41[11.61%] and in 16 [4.53%] subjects, normal type A tympanograms were obtained. Increased number of glue ear were encountered with increasing height from sea level

Broken tracheostomy tube flanges in the tracheo-bronchial region

A young adult tracheostomy dependent male, 25 years of age having quadriplegia due to cerebrovascular accident, following a renal transplantation, was brought to emergency room of E.N.T. Department, Civil Hospital Karachi with dyspnoea and cough. His postero-anterior and ablique skiagram of the chest showed fractured flanges of metallic tracheostomy tube in the lower trachea and right main bronchus. Both the broken flanges of outer tube were removed under local spray of 4% Xylocaine through tracheostome with Stortz's rigid bronchoscope. Pathogenesis of the damages to the metallic tracheostomy tube is discussed