Mutations in the MCPH1 (microcephalin 1) gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS) gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC) samples, and observed that 14/71 (19.72%) informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22%) and 19/25 (76%) OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3′-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a.
ObjectiveTo determine the role of turmeric extract in reducing mucositis in patients undergoing radiotherapy for head and neck cancer.MethodsSixty-one patients who underwent radiotherapy were included in the study and randomised into groups A and B. Patients in group A received 500 mg of turmeric extract (BCM-95) thrice daily, while patients in group B received placebo until radiotherapy completion. All patients were assessed for oral mucositis on a weekly basis during treatment and two months post-treatment using the National Cancer Institute Common Terminology Criteria for Adverse Events and World Health Organization criteria.ResultsBoth groups had a similar grade of mucositis in first two weeks of treatment. The severity of mucositis was progressive in the control group, with four patients developing grade 3 mucositis by week four. In group A, however, the majority of patients (73.3 per cent) had grade 1 mucositis after four weeks of treatment. The difference was statistically significant from the third week onwards (p < 0.001).ConclusionTurmeric extract reduces the incidence and severity of radiation-induced mucositis, which can benefit patients undergoing radiation for head and neck cancer.
Introduction:Oral squamous cell carcinoma (OSCC) is seen worldwide but is more common in India. Lymph node (LN) metastasis has been shown to be the strongest prognostic factor in OSCC. Many histopathological and immunohistochemical markers have been studied to predict the LN metastasis.Aims:To identify clinicopathological factors and immunohistochemical (IHC) biomarkers which predict cervical metastasis in OSCC patients.Study and Design:A total of 105 cases of OSCC were taken up for our study. Histopathological parameters such as tumor thickness, depth, degree of differentiation, pattern of invasion (POI), lymphovascular and neural invasion were assessed. IHC was done on all cases using antibodies against Ki-67, cyclin D, E-cadherin, p53, CD31 and each antibody was assessed according to the standard protocol.Statistical Analysis:To calculate the relation between clinical, histopathological parameter, IHC marker and the occurrence of LN metastasis, chi-square test was used. Variables were tested using multivariate logistic regression method to assess the predictive significance.Results:Out of 105 cases studied, 29 cases showed LN metastasis. Maximum numbers of cases affected were females with involvement of buccal mucosa. We found significant association of cervical LN metastasis with high grade of differentiation, lack of E-cadherin expression, high Ki-67 and cyclin D1 expression. In our study; tumor depth, thickness, extent of peritumoral lympho-plasmacytic infiltration, presence of eosinophils, tumor nest type, p53 and microvessel density (MVD) showed no significant correlation.Conclusion:Significant association of cervical LN metastasis with high grade of differentiation, lack of E-cadherin expression, high Ki-67 and cyclin D1 expression was seen.
ObjectiveTo evaluate the margins of resected specimen of oral squamous cell carcinoma (SCC) and to document the surgical margin (measured at the time of resection) and margins at the time of pathological examination (after immersion of the specimen in formalin).MethodsPatients who were diagnosed and confirmed with squamous carcinoma of buccal mucosa were included in the study. Patients underwent resection of the tumor with a margin of 1 cm. Soon after resection, the distance between outermost visible margin of the tumor and the margin of the specimen was measured and documented. Specimens were fixed in 10% formalin and submitted for gross and histopathological examination. The closest histopathologic margin was compared with the in situ margin (10 mm) to determine and document any shrinkage of the margin and the percentage of discrepancy if any.ResultsA total of 52 specimens were collected from patients between January 2014 and December 2014. All specimens were obtained from the oral cavity (n = 52) of which 43 (82.7%) were squamous cell carcinoma and 9 (17.3%) were verrucous variant of squamous cell carcinoma. The average decrease in tumor margins measured after fixation in formalin was found to be statistically significant (P < 0.05) in 65% of cases.ConclusionTumor margin shrinks significantly after formalin fixation by about 25%. The operating surgeon and pathologist should be well aware of such changes while planning for further management thereby ensuring adequate margin of resection and adjuvant treatment wherever required to prevent possible local recurrence of the disease.
ObjectiveTo evaluate the usefulness of supraclavicular artery flap in reconstruction of defects following resection of buccal mucosa cancer.MethodsTwenty-five patients who presented to R.L Jalappa Hospital and Research centre and diagnosed as squamous cell carcinoma of buccal mucosa staged T2 and above were included in our study. All patients underwent wide excision of tumour and neck dissection. Six patients underwent hemi-mandibulectomy while 4 patients underwent marginal mandibulectomy depending on extent of the tumour along with neck dissection. The defect following surgery was reconstructed using the supraclavicular artery flap and were followed up for minimum 6 months during which they were assessed for the functional and aesthetic outcome using a scoring system. The details of the scoring system comprised of 7 attributes. Each attribute was given a score of 10 if the patients experienced that attribute, while a score of 0 was given if the patient did not experience that particular attribute.ResultsSeven (28%) patients had complete necrosis of the flap. One patient had a local recurrence 2 months following surgery and was lost to follow up. The remaining 17 patients were followed up for a minimum of 6 months and a scoring system was adopted to evaluate the functional and aesthetic outcome of the supraclavicular flap. We observed that 14 patients had an excellent outcome score (58%), 3 patients had a good outcome score (13%), while 7 patients (28%) had flap necrosis.ConclusionsWe find the supraclavicular flap to be safe, technically simple, sensate, thin, pliable and reliable regional fasciocutaneous flap in reconstructing intra oral defects. Preserving the external jugular vein and sacrificing supraclavicular nerves give good outcome.
Locally advanced oral cancers extending to infratemporal fossa (ITF) are a challenge to head and neck surgeons. These tumors are classified as T whenever the masticator space (MS), pterygoid muscles (PM), and pterygoid plates (PP) are involved according to AJCC classification. Until recently, these tumors were considered inoperable and treated only with palliative intent. However, a few studies in the last decade showed that many of these tumors could be resected with a reasonably favorable prognosis by compartment resection of ITF, particularly when the tumor was below sigmoid notch of mandible. A few studies attempted to downstage these tumors by neo-adjuvant chemotherapy before attempting resection. Oral Squamous cell carcinoma has a high prevalence in South India. Majority of these patients are females addicted to tobacco quid chewing and present with locally advanced disease. In this retrospective analysis, we evaluated the outcome of treatment of oral squamous cell carcinoma extending to ITF and staged T in 52 patients. All patients underwent Composite resection including compartment resection of ITF followed by adjuvant treatment. 20 patients had received neo-adjuvant chemotherapy. Pectoralis major myocutaneous flap was the mainstay of reconstruction. After mean follow-up of 2 years, 31 patients are alive and disease free. 14 patients had local recurrence in ITF and 2 patients had recurred in cervical nodes. 8 patients died due to disease and 6 are on palliative care. Neo-adjuvant chemotherapy did not benefit the outcome. Close margins of resection, extra nodal spread from lymph nodes and supra notch and involvement of posterior part of ITF were factors which predisposed to recurrence.
The aim of this study is to conceive a method of raising an island PMMC flap, so as to circumvent its drawbacks of bulk, flap length and the difficulty of developing this flap in female patients. And to consider island PMMC flap as a viable reconstructive option in head and neck surgeries, especially in peripheral centres. Ours is an experimental case series. The study was done at Sri Devaraj URS Medical college, Tamaka, Kolar. Between 2009 and 2010, head and neck reconstruction was performed using this method in 20 patients who had oral cancer (18), carcinoma supraglottis (1) and mucoepidermoid carcinoma parotid (1). The patients age ranged from 16 to 75 years, and there were 15 women and 5 men. Nineteen of our patients underwent primary surgery and one patient was operated for residual disease. In (16) patient, island pmmc flap was used for intra oral closure. In (4) patients the flap was spiraled for providing skin cover. Four patients developed complications. Three were minor complications of margin necrosis and wound dehiscence, which were managed conservatively. One patient developed orocutaneous fistula, which required secondary suturing. None of our patients had a total necrosis of the flap. Island PMMC flap is still a very useful and viable option for reconstruction in head and neck surgeries, especially in lateral gingivo buccal tumours and other head and neck tumours. In institutions where microvascular expertise is not available, island PMMC flap can be an alternative with results comparable to that of free tissue transfer.
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