MiR-144/451a cluster synergistically modulates growth and metastasis of Oral Carcinoma.

OBJECTIVES: MicroRNA (miRNA) clusters co-transcribe and function in a coordinated fashion mediating synergistic or antagonistic regulatory effects. MiR-144 and miR-451a are deregulated in various cancers but the combined regulatory role of miR-144/451a cluster in oral squamous cell carcinoma (OSCC) remains unexplored. In the present study, we studied the synergistic effect of miR-144/451a cluster on oral cancer progression. MATERIALS AND METHODS: miR-144 and miR-451a expression was explored in OSCC cell lines by quantitative real-time PCR (qRT-PCR). Proliferation, wound healing, migration and invasion, spheroid formation, and colony formation assays were performed after transfection with miR-144-3p, miR-451a, miR-144-5p, and co-expressed miR-144/451a. Expression of putative target genes was analyzed using qRT-PCR and Western blotting. RESULTS: miR-144 and miR-451a were downregulated in all cell lines. The cell viability and stemness of cancer cell lines were unaltered when treated with miRNA mimics. However, co-expressed miR-144/451a significantly reduced the migratory, invasive, and clonogenic potential of cells than individual miRNAs. CONCLUSION: miR-144/451a cluster functions as a tumor suppressor in OSCC by inhibiting cancer cell invasion, migration, and clonogenic potential.

Spectrum of malignant scalp tumours and its impact on management-a tertiary care cancer centre experience.

BACKGROUND: Tumours on the scalp are diverse and often exhibit site- and histology-specific characteristics. Reconstructing the scalp after oncological resection has always been challenging because of its unique anatomy. METHODOLOGY: A retrospective review of patients with malignant scalp tumour operated on at a single institution over 10 years was performed. Data were collected and analysed regarding the scalp tumour profile, treatment, and the outcome of these procedures. RESULTS: Of the 66 patients in our study, 33 (50%) had SCC. In addition to this, 21% were sarcomas, 17% were appendageal carcinomas, 11% were BCCs, and 1% was neuroendocrine carcinoma. Cortical erosion was observed in 6 patients in the CT imaging, all with SCC histology. Among the eight patients with pathological nodal involvement, three had angiosarcoma, three had SCC, one had appendageal carcinoma, and one had neuroendocrine carcinoma. The mean surgical defect size was 67.4 cm2. The surgical defect was reconstructed with local flaps in 58% of patients and primary closure in 27%. Local and systemic recurrence was noted in 25% of patients. Tumour size more than 6 cm, tumour histology (SCC & sarcoma), unplanned margin-positive excision, and residual disease in re-excision had higher recurrence, even though the p-value was not significant. CONCLUSION: Scalp tumours are heterogeneous in their clinical profiles. Often, its tumour biology and microscopic extent are underestimated. High suspicion, histological diagnosis, and clear surgical margins are all requirements in successfully treating scalp tumours. In order to minimize morbidity and restore an aesthetic and functional outcome, it is critical to use the simplest scalp reconstruction whenever possible.

Relationship of vitamin D deficiency with mammographic breast density and triple-negative breast cancer: A cross-sectional study.

Background As breast epithelium is affected by vitamin D, it may have a direct effect on breast density and the risk of breast cancer. Our aim was to study the serum levels of vitamin D in patients with malignant and benign breast disease, and to study the association, if any, between vitamin D levels, mammographic breast density (MD) and molecular subtypes of breast cancer. Methods In this cross-sectional, observational study, we enrolled 162 consecutive adult women with benign and malignant breast masses subjected to mammography and core-needle biopsy. Serum levels of vitamin D were estimated and correlated with MD and with immunohistochemical subtyping of breast cancer. Results The mean vitamin D level in these 162 patients was 12.44 (5.88) ng/ml, with vitamin D deficiency seen in 98%. The mean (SD) vitamin D level in MD type 1 was 16.19 (4.62) ng/ml and it decreased to 7.54 (2.58) ng/ml in MD type 4. High MD was associated with significantly lower vitamin D levels. The mean vitamin D level in patients with benign breast disease (n=102) was 13.73 (5.68) ng/ml, while it was significantly lower in patients with breast cancer (n=60) at 10.26 (5.61) ng/ml. Among patients with breast cancer, the good prognosis luminal A molecular subtype had mean vitamin D level of 12.94 (6.16) ng/ml, whereas the poor prognosis triple-negative subtype had a significantly lower value of 7.68 (3.42) ng/ml. Conclusion Our study shows that vitamin D deficiency has a significant relationship with breast cancer (v. benign breast disease), high MD (showing increased breast cancer risk) and poor prognosis triple-negative breast cancer. Vitamin D deficiency could be an important, potentially modifiable, risk factor for the prevention of breast cancer in susceptible populations.

Comparison Between Efficacy of Transdermal Ketoprofen and Diclofenac Patch in Patients Undergoing Therapeutic Extraction-A Randomized Prospective Split Mouth Study.

PURPOSE: Postoperative pain control is a significant aspect of patient treatment after an oral and maxillofacial surgical procedure. The use of a transdermal patch is one such method to provide postoperative analgesia. The present study was undertaken to investigate the efficacy of a single-dose transdermal patch of ketoprofen compared with that of diclofenac postoperatively after therapeutic extraction of first premolar teeth for patients undergoing orthodontic treatment. PATIENTS AND METHODS: A split mouth randomized clinical trial was conducted of 40 patients aged 15 to 25 years who had required therapeutic extraction of both maxillary and mandibular first premolar teeth bilaterally. A single ketoprofen patch was applied for the first and fourth quadrant extraction, and diclofenac patch was applied for the second and third quadrant extraction after atraumatic therapeutic exodontia at 2 consecutive appointments with the patient under local anesthesia. The data were obtained and analyzed using the Student t test and Shapiro-Wilk test using SPSS software (IBM Corp, Armonk, NY). RESULTS: All 40 patients who had received a single-dose ketoprofen patch had experienced less postoperative pain and did not require a rescue analgesic with a mean visual analog scale (VAS) score of 1.13 ± 0.335 (P < .00001). The patients who had received a diclofenac patch reported comparatively elevated pain scores in the initial 24 hours, with a mean VAS score of 2.0 ± 0.5064 postoperatively, and 20% of the diclofenac treatment arm had required a rescue analgesic. No complications were observed among the patients postoperatively in either treatment arm. CONCLUSIONS: Both the ketoprofen and diclofenac transdermal patches were effective in achieving postoperative analgesia in patients after therapeutic extraction, with ketoprofen superior to diclofenac as a transdermal medicament.

Comparative study to evaluate bone loss during osteotomy using standard drill, bone trephine, and alveolar expanders for implant placement.

STATEMENT OF PROBLEM: Various osteotomy modalities seem to have an impact on the primary and secondary stability of the dental implant. The available literature lacks the comparison of various available osteotomy modalities used for the dental implant placement and its effects on the initial surgical bone removal. PURPOSE: The purpose of this study is to compare and evaluate the osteotomy sites created using standard drill, bone trephine, and alveolar expanders for dental implant surgery. MATERIALS AND METHODS: The study was done on ten goat hemimandibles. Three osteotomy sites were prepared at the inferior border of the mandible using standard drill, trephine, and alveolar expander in each hemimandibles and the sites were subjected to cone-beam computed tomography (CBCT). The CBCT images obtained were compared for the amount of cortical bone and bone marrow loss at osteotomy sites in different techniques. RESULTS: The mean and standard deviation of loss of cortical bone with standard drills, trephines, and alveolar expanders was 3.62 ± 4.216 × 10-2, 3.6 ± 4.681 × 10-16 and 3.15 ± 7.071 × 10-2. At the middle-third region, the loss of marrow bone was 3.38 ± 7.88 × 10-2, 2.15 ± 8.498 × 10-2 and 0.03 ± 9.487 × 10-2, and at lower third region, it was 2.3 ± 4.714 × 10-2, 0.02 ± 6.325 × 10-2, and 0.0, respectively. CONCLUSION: CBCT images showed minimum bone loss with the use of alveolar expander which may be due to the lateral bone condensation rather the removal of the marrow. Trephine showed less marrow removal in comparison to the standard drill used for dental implant surgery.

Does Topical Application of Placental Extract Gel on Postoperative Fibrotomy Wound Improve Mouth Opening and Wound Healing in Patients With Oral Submucous Fibrosis?

PURPOSE: Placental extract has been used as a therapeutic agent with application in various fields of medicine. Placental extract is well known for its effects on wound healing with anti-inflammatory, antiplatelet, and angiogenic effects and is also a biogenic modulator. The present study evaluated the effect of placental extract on wound healing, mouth opening, and postoperative patient discomfort in patients with oral submucous fibrosis treated with fibrotomy with buccal fat pad coverage and coronoidectomy. MATERIALS AND METHODS: Ten subjects with oral submucous fibrosis who presented with mouth opening less than 20 mm were enrolled in the present prospective randomized controlled trial to assess the effects of placental extract on the fibrotomy wound covered with a pedicled buccal pad fat (5 patients allocated to the study group, group S and 5 to the control group, group C). The following criteria were used to analyze the postoperative effect of placental extract on fibrotomy wounds compared with that of the controls: subjective assessment of the wound, postoperative discomfort, and postoperative mouth opening assessed at 1, 2, and 4 weeks postoperatively. RESULTS: The average difference in the preoperative and fourth week postoperative mouth opening for group C was 13.8 ± 2.68 mm and was 21.20 ± 2.77 mm in group S. The median calculated for group C was a 15.0-mm increase in mouth opening and was 20.0 mm in group S. CONCLUSION: The results obtained with topical application of placental extract on fibrotomy wound healing and postoperative mouth opening were superior to those of the control group in whom placental extract was not used.

Schwannoma base of Tongue - Case Report with a Novel Reconstruction Technique.

INTRODUCTION: Schwannomas are benign, slow-growing well-encapsulated neoplasms arising from Schwann cells of nerve sheaths. Oral cavity schwannomas are very rare with an incidence less than 1%. The posterior third of the tongue is not frequently involved. CASE REPORT: We report a rare case of a large tongue base schwannoma in a 44 year old female managed surgically by lateral pharyngotomy approach. A novel reconstruction method involving the use of submental flap is described for the functional reconstruction of the defect. CONCLUSION: Being a rare tumor, schwannoma should not be missed in the differential diagnosis of tongue base tumors. Complete surgical resection is the treatment of choice with recurrence being very rare.

Comparison Between Pre-COVID and Post-COVID Mucormycosis: A Systematic Review and Meta-analysis.

Introduction: Mucormycosis has emerged as one of the most fatal complications arising due to COVID-19, though it has to be mentioned that the disease is capable of causing serious illness even on its own. Objectives: Through this investigation, we would review the threat that mucormycosis poses, in terms of its prevalence and degree of severity both in the pre- and post-COVID world. Materials and Methods: A comprehensive examination of the studies published in online databases turned up 207 papers, 103 of which had undergone in-depth analysis, using both inclusion and exclusion criteria, shortlisting 15 studies that were appropriate for reviewing. Results: The incidence of mucormycosis was linked to coronavirus in 7 of the 15 studies that were chosen. The remaining eight studies had sufferers of various systemic diseases, like HIV/AIDS and diabetes. Discussion: All the cases suffered diabetes mellitus. Regardless of the time period of the chosen article, corticosteroids and antifungal medications were administered to all patients. There were noticeable differences in terms of mortality, predisposing factors, and virulence between pre-COVID and post-COVID mucormycosis. Summary and Conclusion: The prevalence of systemic conditions such as diabetes in cases of mucormycosis has remained the same even after the incidence of this pandemic, showing that the basic treatment modalities continue to remain the same irrespective of the damage that corona virus has caused to the sufferer, although mucormycosis arising due to COVID-19 differs from mucormycosis that was incident before the advent of the pandemic.

Intrathyroidal thymic carcinoma not so indolent a neoplasm?

ABSTRACT: Intrathyroidal thymic carcinoma (ITC) is a very rare malignant epithelial tumor of the thyroid gland with thymic epithelial differentiation. Here, we are reporting the case of an eighty-year-old man who at presentation had extrathyroidal spread to the larynx and metastasis to regional lymph nodes. Though the tumor had a relatively low-grade morphology, there were areas of high mitotic activity with areas of necrosis. The classically described ivory-white gross appearance of the tumor, histomorphology of thick bands dividing the tumor into lobules, squamous cell differentiation, tight whorls of cells resembling Hassall's corpuscle, and areas showing dense lymphocytic infiltration, together with an immunoprofile of CD5, Ckit, Tumor protein 63 (p63), and B-cell lymphoma 2 gene (bcl2) positivity, helped in diagnosing this rare entity. Though classically ITC is said to have a good prognosis, cases with spread to adjacent organs and lymph node metastasis may not have an indolent course.

Predictive factors for nodal recurrence in differentiated thyroid cancers.

INTRODUCTION: Differentiated thyroid carcinoma usually has a good prognosis. Primary treatment is surgery, followed by radioactive iodine ablation based on risk stratification. The incidence of local and distant recurrence is 30%. Recurrence can be managed surgically or with multiple cycles of radioactive iodine ablation. There are multiple risk factors for structural disease recurrence proposed by the American Thyroid Association. In this study, we attempted to study the risk factors of structural recurrence in differentiated carcinoma thyroid and the pattern of recurrence in patients with node negative thyroid cancer who underwent total thyroidectomy. METHODOLOGY: This study selected a retrospective cohort of 1498 patients with differentiated thyroid cancer: out of these, 137 patients who presented after thyroidectomy with cervical nodal recurrence from January 2017 to December 2020 were included. The risk factors for central and lateral lymph node metastasis were analysed by univariate and multivariate analyses, including age, gender, T-stage, extrathyroidal extension, multifocality and high-risk variants. In addition, the presence of TERT/BRAF mutations was studied as a risk factor for central and lateral nodal recurrence. RESULTS: Out of 1498 patients, 137 who fit the inclusion criteria were analysed. Majority were female (73%); mean age was 43.1 years. Lateral compartment neck nodal recurrence was more common (84%), while isolated central compartment nodal recurrence occurred only in 16%. Most recurrences were seen in the first 1 year (23.3%) or after 10 years post-total thyroidectomy (35.7%). On univariate variate analysis, multifocality, extrathyroidal extension and high-risk variants stage were significant factors for nodal recurrence. However, on multivariate analysis for lateral compartment recurrence, multifocality, extrathyroidal extension and age were found to be significant. On multivariate analysis, multifocality, extrathyroidal extension and presence of high-risk variants were significant predictors of central compartment nodal metastasis. ROC curve analysis showed AUC for ETE (AUC-0.795), multifocality (AUC-0.860), presence of high-risk variants (AUC-0.727) and T-stage (AUC-0.771) as sensitive predictive factors for central compartment. 69 percent patients with very early recurrences (<6 month) had TERT/BRAF V600 E mutations. CONCLUSION: In our study, we have noted extrathyroidal extension and multifocality as significant risk factors for nodal recurrence. BRAF and TERT mutations are associated with aggressive clinical course and early recurrences. There is limited role of prophylactic central compartment node dissection.

Treatment outcomes of squamous cell carcinoma of the lip: A retrospective study.

Oral and lip cancer is the most common type of cancer among males in India. Early stage tumours of the lip (stages I and II) are treated with single modality treatment, using either radiotherapy [external beam radiotherapy (EBRT) or brachytherapy] or surgery. Locally advanced tumours (stages III and IVa) are treated with surgery followed by adjuvant treatment. The aim of the present study was to retrospectively evaluate the clinical profile and treatment outcomes of patients with squamous cell carcinoma of the lip who were treated with radical intent at the Regional Cancer Centre (Thiruvananthapuram, India). For this purpose, a total of 120 patients treated with radical radiotherapy (brachytherapy or EBRT) or surgery with or without adjuvant treatment between January 2010 and December 2016 were eligible for the analysis. Kaplan-Meier analysis was used to generate the survival outcomes. Univariate and multivariate analyses were performed to determine the impact of various patient- and tumour-related factors and treatment modality on outcomes. At a median follow-up time of 67.6 months, the disease-free survival (DFS) and overall survival (OS) rates at 4 years for the entire cohort were 69.1 and 86.7%, respectively. The 4-year OS rates for patients with stage I, II, III and IV disease were 88.9, 95.2, 86.8 and 75.3%, respectively, and the DFS rates were 83.6, 69.5, 78.8 and 42.9%, respectively. Primary tumour (P=0.025), nodal (P=0.005) and composite clinical (P=0.006) stage were found to be significant factors affecting DFS rates in the univariate analysis. However, only the nodal stage (P=0.005) was found to be a significant factor affecting DFS rates in the multivariate analysis. On the whole, the present study demonstrates that the outcomes of patients with lip carcinoma are favourable when treated at the early stages, and the results from this series are in line with those already published.

Clinico pathological characteristics and survival outcome in oral cavity cancer with masticator space involvement (T4b) - A single institutional experience.

INTRODUCTION: Oral cavity cancer with the masticator space involvement is considered as very advanced localised diseas e and staged as T4b in AJCC 8th edition. NCCN guidelines consider this as inoperable. This study intends to compare the different treatment modalities in T4b oral cavity cancer and their impact on survival. PATIENTS AND METHODS: This is a retrospective study of 150 patients with T4b oral cavity ca, from 2013to 2015 and follow up data till 31 st July 2019 were collected. All patients had biopsy proven SCC and CT evidence of masticator space involvement. RESULTS: Total of 150 patients were included. 102 patients had received curative treatment and 48 patients had received palliative treatment. In the curative group 84% were treated with surgery and adjuvant treatment and remaining had received RT with or without chemotherapy. 90% patients in the surgically treated group had attained margin negative resection. 4 year OS in the curatively treated group was 58.9% and in the palliative group was 12%. The surgically treated patients in the curative arm had a significant survival advantage over the patients who had received only RT with or without chemotherapy, (63.5% v/s 34%, p = 0.001). CONCLUSION: Curatively treated oral cavity cancer with masticator space involvement has survival outcome comparable to the published survival data of those without masticator space involvement. Radical intent treatment, preferably surgery should be offered to all patients with masticator space involvement, if negative margin is anticipated from preoperative imaging.

Papillary Thyroid Carcinoma Arising from Thyroglossal Cyst-an Institutional Experience over a Decade.

Papillary carcinoma constitutes 80% of thyroglossal duct cyst carcinoma (TGCC). The mainstay of treatment for TGCC is Sistrunk procedure. Due to lack of clear-cut guidelines in managing TGCC, the role of total thyroidectomy, neck dissection and adjuvant radioiodine therapy is still debatable. This was a retrospective study which included cases of TGCC treated in our institution over a period of 11 years. The aim of study was to assess the need for total thyroidectomy in management of TGCC. Patients were divided into two groups based on the surgical treatment they underwent and the treatment outcomes were compared. The histology was papillary carcinoma in all cases of TGCC. Overall, 43.3% of TGCCs had a focus of papillary carcinoma in total thyroidectomy specimen. Lymph node metastasis was noted only in 10% of TGCC and not identified in isolated papillary carcinoma confined to thyroglossal cyst. 7-year overall survival (OS) for TGCC was 83.1%. Prognostic factors like extracapsular extension or lymph node metastasis did not affect OS. Addition of total thyroidectomy and neck dissection to Sistrunk procedure did not offer any survival advantage. In a case of TGCC, FNAC should be done from any clinically suspicious thyroid nodules or lymph nodes. TGCC has a good prognosis following treatment and none of the cases in our series has disease recurrence during follow-up. Sistrunk procedure was an adequate procedure for treatment of TGCC with clinically and radiologically normal thyroid gland.

Demographic and clinical characteristics of primary lung cancer patients in Kerala: Analysis of data from six teaching centers.

Background: Lung cancer continues to be the leading cause of cancer-related deaths in men and women. A breakdown by level of economic development shows no differences in cancer deaths in men but a higher rate of lung cancer deaths in women in industrialized countries as compared with developing nations. The risk factors for lung cancer most commonly include lifestyle, environmental, and occupational exposures. The role these factors play varies depending on geographic location, sex and race characteristics, genetic predisposition, as well as their synergistic interactions. Materials and Methods: It was a hospital-based registry, wherein hospitals were selected from three zones-north, central, and south zones of Kerala. The study was registered with clinical trial registry of India with Registration No. CTRI/2021/02/031299. Registry of lung cancer patients was prepared at all sites and institutional ethical clearance was received from all sites. All patients with primary lung cancer, histologically proven of all age groups were included in the study. Results: A total of 761 patients were registered from six teaching hospitals in Kerala who were diagnosed with primary lung cancer during the period 2017-2019. The mean age of the study population was 65.1 ± 10.2 years. Of all, 81.1% of them were males and 18.9% were females. Histologically, 56.4% had adenocarcinoma and 25.6% had squamous cell carcinoma. Conclusion: It was observed that the proportion of females diagnosed with primary lung cancer is increasing. Patients get diagnosed at a later stage of the disease, which calls for screening and early detection of lung cancer. As it accounts for the highest mortality among all other cancers, there is high scope for prevention and screening strategies.

Impact of COVID-19 on Disease Progression and Postoperative Complications in Patients with Head and Neck Cancer.

The COVID-19 pandemic has created a remarkable challenge for the healthcare system. The delayed presentation, diagnosis, and treatment of head and neck cancer during the COVID-19 pandemic is expected to adversely affect outcomes. COVIDSurg collaborative group in 2020 concluded surgery ≥ 4 weeks after a positive COVID-19 swab result was associated with a lower risk of postoperative mortality. The aim of this study is to assess the disease progression due to COVID-19 infection in patients with head and neck cancer planned for surgery and to analyze the postoperative complications in head and neck cancer patients who underwent surgery after COVID-19 infection. This is an ambispective observational study and included patients with head and neck cancer who recovered from COVID-19 infection and underwent surgery from June 2020 to May 2022. There were a total of 1849 patients with head and neck cancer operated in the mentioned study period during COVID-19 pandemic. One hundred fifty-nine patients had documented COVID-19 infection. One hundred two patients had oral cavity carcinoma (64%), and 38 patients had thyroid carcinoma (23.8%). Early disease was noted in 49 patients (30.8%) and locally advanced disease in 108 patients (67.9%). Mean duration of delay in surgery was 4 weeks. Disease progression was noted in 27 patients (17%) out of which 15 patients were inoperable. Thirty-seven out of 159 patients (23%) had postoperative complications, and it included 2 mortality. There was increased trend noted in pulmonary complications and hemorrhage when compared to pre-COVID-19 era. Due to COVID-19 pandemic, delayed elective head and neck cancer surgery has resulted in higher rates of inoperability. COVID-19 has been associated with increased postoperative pulmonary complications and hemorrhage.

Comparison of preoperative assessment tools in older patients undergoing cancer surgery: A prospective study.

INTRODUCTION: Surgery in older adults with cancer is complex due to multiple age related confounding factors. There are many scoring systems available for preoperative risk stratifications of older patients. Currently very few prospective studies comparing the various commonly used scales are available. This is the first study which compares the established preoperative risk assessment tools of Eastern Cooperative Oncology Group Performance Scale (ECOG) and American Society of Anaesthesiologists Physical Status Scale (ASA) with frailty scores of Modified Frailty Index (MFI) and Clinical Frailty Scale (CFS). MATERIAL AND METHODS: This is a prospective observational study of older patients with cancer who underwent oncosurgery in a tertiary cancer centre during the one-year study period. Patients were scored on the CFS, MFI, ASA and ECOG scales. All patients were followed up for 30 days immediately following surgery and their post operative complications were documented. Univariate and multivariate analyses were done and a p value of ≤0.05 was considered statistically significant. RESULTS: Of the 820 patients studied, 15.6% had prolonged hospital stay, 9.1% had 30-day morbidity, 0.7% had readmission, and mortality was 1.1%. High-risk scores on the ASA and CFS were significantly associated with prolonged postoperative stay, readmission, morbidity, and mortality (p < 0.05). High-risk scores on the ECOG was significantly associated with prolonged hospital stay (p = 0.027), 30-day morbidity (p = 0.003), and mortality (p = 0.001), but not with readmission. There was no significant association between MFI score and the postoperative variables studied (p > 0.05). On multivariate analysis, morbidity was significantly associated only with male gender (p = 0.015), higher cancer stage (p = 0.005), higher ASA score (p = 0.029), and prolonged hospital stay (p = 0.001). Mortality was significantly associated only with emergency surgery (p = 0.012) and prolonged hospital stay (p = 0.004), and prolonged hospital stay was significantly associated with advanced cancer stage (p = 0.001) and emergency surgery (p = 0.02). CONCLUSIONS: In older patients undergoing cancer surgery, ASA and CFS are predictors of prolonged postoperative stay, morbidity, mortality, and readmission. A high-risk ECOG score is predictive of prolonged post operative stay, 30-day morbidity, and mortality, but not of readmission. Score on MFI is not a predictor of postoperative outcomes. Newer predictive tools which include cancer- specific factors are required for better management of these patients.

Mucosal Melanomas of the Oral Cavity: A Tertiary Care Centre Experience of Surgically Treated Cases.

Mucosal melanoma of oral cavity (MMO) is a relatively rare tumour comprising of 40% of all head and neck mucosal melanomas. This study assessed the treatment outcomes and factors affecting prognosis in oral cavity mucosal melanomas. The clinical case records of 25 cases of oral cavity mucosal melanomas treated in our institution during 2003-2013 were retrospectively reviewed. Various clinicopathological parameters were taken into consideration and statistical analysis done by Kaplan-Meier method and Cox's proportional hazards model. The most common sites of MMO were upper alveolus and hard palate (64%) followed by lower alveolus (28%). 57.1% mucosal melanomas of hard palate and upper alveolus had associated metastatic lymph nodes whereas all cases of MMO of lower alveolus had lymph node metastasis. Disease failure at distant sites was higher than that at primary site or lymph nodes. The most common site of distant metastases was brain. The 5-year OS for treated cases was 23.8% and among subsites, MMO of hard palate and upper alveolus had the highest survival. Metastasis to lymph nodes and bone infiltration by tumour significantly decreased the survival. Recurrence at primary site had the worst prognosis. MMO with lymph nodal involvement and bone erosion had poor prognosis. Due to high chances of lymph node metastases and disease recurrence in lymph nodes following treatment, it is essential to do an elective neck dissection for all cases of MMO. Disease failure at primary site was an independent predictor of outcome in MMO.

Correlation of TIRADS and Bethesda Scoring Systems with Final Histopathology of Thyroid Nodules - An Institutional Experience.

Fine needle aspiration cytology (FNAC) reduces the number of unnecessary thyroid surgeries for patients with benign nodules and appropriately triages patients with thyroid cancer to appropriate treatment. This was a observational study done on cases presenting with clinical suspicion of thyroid malignancy which underwent ultrasonography followed by FNAC of thyroid nodule. Ultrasonographic characterization of nodules was based on Thyroid Imaging Reporting and Data System (TIRADS) and cytology reporting was based on Bethesda system. All recruited patients underwent thyroidectomy. Pre-operative cytology and ultrasonography features were compared with final histopathology report. In our study, Bethesda system of cytology reporting for thyroid nodules had a better sensitivity, specificity and diagnostic accuracy than TIRADS system of ultrasound reporting. Bethesda system in FNAC had a larger area under the ROC curve (0.91) as compared to ultrasound TIRADS (0.70). Malignancy rate of TIRADS 5 nodules was 97.1% with significant p value (0.022). 100% of Bethesda VI lesions were malignant according to final histopathology report. Ultrasound TIRADS could pre-operatively predict malignancy in 63.6% of indeterminate thyroid nodules which were malignant according to post-operative histopathology. The overall concordance of ultrasound TIRADS, Bethesda system and histopathology was 69.8%. Higher TIRADS and Bethesda scoring among thyroid nodules was associated with increased risk of malignancy. US TIRADS is a good predictor of malignancy in indeterminate thyroid nodules.

Combinatorial treatment with Gefitinib and Bay11-7085 sensitizes primary Gefitinib-resistant OSCC cells by influencing the EGFR- NFκB signaling axis.

EGFR-targeted therapies are reported to yield modest effect in OSCC. Activation of NFκB signaling is considered as molecular driver of EGFR inhibitor resistance in various cancers. In this scenario, present study focused on the molecular crosstalk between EGFR and NFκB signaling pathways and its therapeutic importance in OSCC. The EGFR- NFκB p65 co-expressed human OSCC cell lines UPCI:SCC066, UPCI:SCC040 and UM-SCC083B were used for in vitro studies. Recombinant human EGF, siRNAs, Western blot and qRT-PCR were used to dissect the molecular crosstalk between EGFR-NFκB signaling pathways in OSCCs. The effect of NFκB p65 knockdown on cancer hallmarks was studied by respective functional assays and RNA-Seq analysis was performed to identify the differentially expressed genes upon NFκB p65 knockdown. Gefitinib and Bay 11-7085 combination treatment was done to study the chemotherapeutic potential of EGFR- NFκB axis. Significant positive correlation between EGFR and NFκB p65 expression was observed in Head and Neck TCGA data set. EGFR induction or knockdown respectively stimulate or impair the NFκB signaling in EGFR- NFκB p65 co-expressed OSCC cell lines. NFκB p65 knockdown causes apoptosis and suppresses the viability, colony formation, migration, invasion, and spheroid formation. Using RNA-seq analysis, we identified PIK3CD as the NFκB target gene, which is commonly involved in these functions. Gefitinib and Bay 11-7085 combination treatment was found to be useful in chemosensitizing the Gefitinib-resistant OSCC cells by capitulating the EGFR- NFκB signaling axis. Combination treatment using Gefitinib and Bay 11-7085 enhanced the apoptosis and reduced cell viability and colony formation in a synergistic way. Our data demonstrated that EGFR-NFκB signaling axis plays a key role in the pathogenesis of OSCCs. Therefore, simultaneous therapeutic intervention of these pathways may be a good alternative approach for the management of OSCCs.