A novel 3-miRNA network regulates tumour progression in oral squamous cell carcinoma.

BACKGROUND: Late diagnosis is one of the major confounders in oral squamous cell carcinoma (OSCC). Despite recent advances in molecular diagnostics, no disease-specific biomarkers are clinically available for early risk prediction of OSCC. Therefore, it is important to identify robust biomarkers that are detectable using non-invasive liquid biopsy techniques to facilitate the early diagnosis of oral cancer. This study identified potential salivary exosome-derived miRNA biomarkers and crucial miRNA-mRNA networks/underlying mechanisms responsible for OSCC progression. METHODS: Small RNASeq (n = 23) was performed in order to identify potential miRNA biomarkers in both tissue and salivary exosomes derived from OSCC patients. Further, integrated analysis of The Cancer Genome Atlas (TCGA) datasets (n = 114), qPCR validation on larger patient cohorts (n = 70) and statistical analysis with various clinicopathological parameters was conducted to assess the effectiveness of the identified miRNA signature. miRNA-mRNA networks and pathway analysis was conducted by integrating the transcriptome sequencing and TCGA data. The OECM-1 cell line was transfected with the identified miRNA signature in order to observe its effect on various functional mechanisms such as cell proliferation, cell cycle, apoptosis, invasive as well as migratory potential and the downstream signaling pathways regulated by these miRNA-mRNA networks. RESULTS: Small RNASeq and TCGA data identified 12 differentially expressed miRNAs in OSCC patients compared to controls. On validating these findings in a larger cohort of patients, miR-140-5p, miR-143-5p, and miR-145-5p were found to be significantly downregulated. This 3-miRNA signature demonstrated higher efficacy in predicting disease progression and clinically correlated with poor prognosis (p < 0.05). Transcriptome, TCGA, and miRNA-mRNA network analysis identified HIF1a, CDH1, CD44, EGFR, and CCND1 as hub genes regulated by the miRNA signature. Further, transfection-mediated upregulation of the 3-miRNA signature significantly decreased cell proliferation, induced apoptosis, resulted in G2/M phase cell cycle arrest and reduced the invasive and migratory potential by reversing the EMT process in the OECM-1 cell line. CONCLUSIONS: Thus, this study identifies a 3-miRNA signature that can be utilized as a potential biomarker for predicting disease progression of OSCC and uncovers the underlying mechanisms responsible for converting a normal epithelial cell into a malignant phenotype.

Salivary Exosomal miRNA-1307-5p Predicts Disease Aggressiveness and Poor Prognosis in Oral Squamous Cell Carcinoma Patients.

Background: Salivary exosomal miRNAs as biomarkers facilitate repeated sampling, real-time disease monitoring and assessment of therapeutic response. This study identifies a single salivary exosomal miRNA prognosticator that will aid in improved patient outcome using a liquid biopsy approach. Method: Small RNA and transcriptome sequencing profiles of tumour tissues (n = 12) and salivary exosomes (n = 8) from oral cancer patients were compared to their non-cancerous counterparts. We validated these results using The Cancer Genome Atlas database and performing Real-time PCR on a large patient cohort (n = 19 tissue samples; n = 12 salivary exosomes). Potential target genes and the miRNA-mRNA networks and enriched biological pathways regulated by this microRNA were identified using computational tools. Results: Salivary exosomes (size: 30-50 nm) demonstrated a strong expression of CD47 and detectable expression of tetraspanins CD63, CD81 and CD9 by flow cytometry. miR-1307-5p was exclusively overexpressed in tissues and salivary exosomes of oral cancer patients compared to their non-cancerous counterparts. Enhanced expression of miR-1307-5p clinically correlated with poor patient survival, disease progression, aggressiveness and chemo-resistance. Transcriptome analysis suggested that miRNA-1307-5p could promote oral cancer progression by suppressing THOP1, EHF, RNF4, GET4 and RNF114. Conclusions: Salivary exosomal miRNA-1307-5p is a potential prognosticator for predicting poor survival and poor patient outcome in oral cancers.

A Case Report and Review of Literature: Cribriform-Morular Variant of Papillary Carcinoma.

We describe a case of cribriform morular variant of papillary thyroid carcinoma which is a rare subtype. We report a case of a 26 year old female who presented with a thyroid tumour without colonic manifestations. She underwent a total thyroidectomy with central compartment neck dissection. Her histopathology report showed Cribriform-Morular variant, Papillary carcinoma of the left lobe of thyroid. Focal Angio-invasion was present. Even in sporadic presentations of these variants, screening colonoscopy, genetic counselling and screening of family members should be invariably considered as many a time thyroid malignancy presents many years prior to colonic manifestations.

Efficacy of Single Transverse Neck Incision for Modified Radical Neck Dissection.

BACKGROUND: To assess the viability of the single transverse neck incision (STNI) for modified radical neck dissection and to analyze the yield of lymph nodes using this approach. MATERIALS AND METHODS: We conducted a prospective observational study in the Department of Head and Neck Surgical Oncology at our Tertiary Cancer Care Centre from November 2013 to May 2017. RESULTS: A total of 257 patients underwent surgical treatment for malignant tumors of the head and neck which included 265 modified radical neck dissections (eight bilateral and 249 unilateral). Average of total dissected nodal yield was 37.07. Average yield of positive neck nodes was 2.78. CONCLUSION: Single transverse neck incision is an acceptable technique for modified radical neck dissection as it provides adequate surgical exposure for achieving optimal nodal clearance with little technical difficulty.

Conservative Curative Larynx Preserving Surgery for Subglottic Soft Tissue Recurrence Reinforced with Fascia-Lata and Strap Muscles.

For early cancers of vocal cords, trans oral laryngeal surgery (TOLS) and curative radiotherapy (RT), have remained mainstay of treatment. Soft tissue recurrence in laryngeal cancers is not much documented, leading to absence of guidelines to deal with it, salvage total laryngectomy being the treatment of choice. We present a tailormade surgical procedure for limited soft tissue recurrence of glottic cancer extending into subglottic anterior soft tissue reinforced with fascia lata and strap muscles, previously treated with TOLS and/or RT.

Does Continuing Medical Education (CME) Activity Contribute to Learning Gain: An Objective Evaluation.

Continuing medical education (CME) and work-shops go a long way to update and refresh medical education of the medical practitioners and help them to stay updated about latest advances in the medical field which helps them to impart latest and better treatment to the patients. This article aims at reporting the evaluation of the effectiveness of the learning in terms of knowledge gained immediately after the workshop and to objectively quantify the knowledge gain from the CME program. Pre- and post-CME survey of knowledge by the way of multiple choice question questionnaire was used to assess the efficacy of the CME and the learning gain of the participants. 42 participants were included in the assessment of the gain in knowledge after the CME. An increase of 17.9% in the scores of the participants was seen at the end of the CME, with a learning gain of 38%. Educational activity like CME can improve the knowledge base of the intended participants. Further research is required to evaluate if education delivered in a short workshop of this nature is retained for any length of time and if it results in any change in practice that affects health outcomes.

A rare case of sinonasal glomangiopericytoma post operative accidental diagnosis and managment-A case report.

INTRODUCTION: Glomangiopericytoma is a rare neoplasm of low malignant potential. It is a rare type of haemangiopericytoma located in nasal cavity. This neoplasm has good prognosis and complete surgical excision is treatment of choice. This case report is representing one such neoplasm. This reporting is done in line with the SCARE criteria (Agha et al., 2018 [1]). CASE PRESENTATION: We presenting a case of 54 year old male patient from upper socioeconomic status who presented at our institution with history of surgery (endoscopic sinus surgery with Septoplasty) 15 days back. A Final histopathology report suggested glomangiopericytoma. Since primary surgery was not done as per oncologic principals, patient was advised for adjuvant radiation. At our institute patient was evaluated again. Revision surgery was done. Patient was discharged next day. DISCUSSION: Glomangiopericytoma is a rare neoplasm with incidence of less than 0.5% of all neoplasms of sinonasal cavity. Prognosis is very good after complete surgical excision. It often confuses clinicians with nasal polyps. Here also patient was operated initially considering as benign polyposis outside. Patient was re-operated again to ensure the complete clearance. CONCLUSION: This is the typical case of converting dual modality treatment to single modality with the help of knowledge, communication, transparent team work. This also a rare type of neoplasm and by reporting this rare case we are contributing to data pool of nasal tumors where lack of reporting is major obstacle in the formation of uniform treatment guidelines.

Role of Imaging in Clinically Occult Isolated Intrathyroidal Metastasis from Squamous Cell Carcinoma of Tongue: An Unusual Case Series.

Metastasis to the thyroid gland is rare; furthermore, intrathyroid metastasis from head and neck squamous cell carcinoma (SCC) is very unusual, with only nine previously documented cases four from intrathyroid metastasis from nasopharyngeal carcinoma, two from oral cavity, one each from oropharynx, larynx, and parotid. The reported case series are unique in nature and illustrates the role of fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) and ultrasound-guided biopsy in diagnosing clinically occult isolated intrathyroidal metastasis, which helps in the best management for an isolated intrathyroid metastases. This study details the cases of three patients who were diagnosed with intrathyroidal metastasis from SCC of the tongue by PET-CT, followed by USG-guided biopsy, who were treated with either surgery and or chemotherapy. Although intrathyroidal metastasis is an uncommon occurrence and signifies poor prognosis, early detection of an isolated intrathyroidal metastasis on imaging in an appropriately selected patients, radical surgery, and/or chemotherapy improve local control and quality of patient's life.

Clinical assessment scoring system for tracheostomy (CASST) criterion: Objective criteria to predict pre-operatively the need for a tracheostomy in head and neck malignancies.

BACKGROUND: Tracheostomy is a mainstay modality for airway management for patients with head-neck cancer undergoing surgery. This study aims to define factors predicting need of tracheostomy and define an effective objective criterion to predict tracheostomy need. METHODS: 486 patients undergoing composite resections were studied. Factors analyzed were age, previous surgery, extent of surgery, trismus, extent of mandibular resection and reconstruction etc. Factors were divided into major and minor, using the clinical assessment scoring system for tracheostomy (CASST) criterion. RESULTS: Sixty seven (13.7%) patients required tracheostomy for their peri-operative management. Elective tracheostomies were done in 53 cases during surgery and post-operatively in 14 patients. All patients in whom tracheostomies were anticipated had a score of seven or more. CONCLUSION: A decision on whether or not an elective tracheotomy in head and neck surgery is necessary and can be facilitated using CASST criterion, which has a sensitivity of 95.5% and a negative predictive value (NPV) of 99.3%. It may reduce post-operative complications and contribute to safer treatment.

Use of 90° Hopkin's Telescopic Examination as an OPD Tool to Clinically Evaluate and Record Oral Cavity Lesions: Our Experience in Early Detection, Especially in Patients with Limited Mouth Opening.

INTRODUCTION: Restricted mouth opening due to premalignant lesions like oral sub-mucous fibrosis, malignancies of oral cavity and postoperative status is very common in Indian patients. It is very difficult to evaluate, document and biopsy the lesions due to inability to access, vast area and diversity of premalignant lesions and subject variations. 90° Hopkin's slender out-patient examination telescope was found useful tool in this. AIM: The aim of the study was to evaluate the use of magnified view and reach of a slender telescope to document and examine the oral cavity for any premalignant and malignant lesions, especially for patients with restricted mouth opening and to study its impact on management. MATERIALS AND METHODS: A 90(0) Hopkin's telescope was used to evaluate and document oral cavity examination in the Out Patients Department (OPD). The data of first 2000 patients was analysed. RESULTS: Difficult to reach areas, where mouth opening was severely restricted was the significant subset. A total of 1394 patients approached OPD for primary diagnosis at our tertiary cancer care centre. Six hundred and six patients were the ones in follow up after treatment in form of Surgery, Chemotherapy or Radiotherapy, or combination. Five twenty three patients (of 1394) with mouth opening ≤ 20mm formed the study group. Telescope guided biopsies were also taken in 50 patients from 56 sites. Serial recordings were compared objectively in premalignant, treatment evaluation and close watch groups. An increase of 5.6% in rate of diagnosis of malignancy was made possible with the help of telescopic examination in patients with mouth opening ≤ 20mm. CONCLUSION: A 90(0) Hopkin's telescopic examination is a useful tool to evaluate and record oral cavity lesions, especially in patients with restricted mouth openings. It is a useful tool for screening high risk group, giving definite advantage of objective evaluation and recording of the lesion. It can also be used to objectively evaluate response of neo-adjuvant chemotherapy and as a teaching tool for the fellows.

Use of Polymethyl Methacrylate-Based Cement for Cosmetic Correction of Donor-Site Defect following Transposition of Temporalis Myofascial Flap and Evaluation of Results after Adjuvant Radiotherapy.

BACKGROUND: Temporalis myofascial flap is a versatile flap for reconstruction of the oral cavity defects, but results in an esthetically compromised deformity at the donor site. We used polymethyl methacrylate (PMMA) cement to correct the volume loss defect caused by temporalis myofascial flap and evaluated its results before and after adjuvant radiotherapy. METHODS: We discuss our experience of using PMMA cement to augment donor-site deformity in 25 patients (17 males, 8 females) between years 2005 and 2009. The primary defect was a result of the ablative surgery for squamous cell carcinoma of the upper alveolar and the buccoalveolar sulcus. A modified curved hemicoronal incision was used as an access for better cosmetic outcome. The volume of cement required was decided during the surgery. RESULTS: All patients are in regular follow-up, alive and free of complications at implant site, except one patient who developed wound dehiscence. The condition of the implant was evaluated by postoperative computed tomographic scan, repeated after adjuvant radiotherapy in cases required. There were no radiation-induced changes in the contour and volume of the implants. Cosmetic result of the implant was reported satisfactory by the patients postoperatively. CONCLUSION: Restoration of the temporal area defect after the temporalis myofascial flap harvest with the use of PMMA cement is an easy and safe method, with excellent esthetic results. The implant is stable and resistant to any changes in contour and loss of volume even after adjuvant radiotherapy, with no added morbidity to the patients.

PET-CT with MR Fusion: Single Comprehensive Preoperative Metastatic Workup in Head and Neck Malignancy: A Case Report.

Head neck cancers (HNC) are the sixth most common cancer worldwide. In presence of the complex anatomy of this region, early diagnosis can sometimes be a challenge. At present for the TNM staging, contrast enhanced CT and MRI are the primary imaging modalities for evaluating T stage of HNSCC. Multiple studies suggest that PET/CT might be superior to conventional imaging (CT or MRI) in initial staging and may alter management and treatment especially when distant metastases are discovered. We present a case of a 35-year-old patient who presented to us with an ulcerative lesion on the left buccal mucosa, which was staged as cT2N0M0, using the conventional radiology. But on subsequent imaging by PET-CT with MR-fusion was upstaged to cT4bN0M0, thus completely changing the management of the patient. With the recent advances in technology leading to fusion of MRI images with PET-CT images have combined the benefits of all three imaging modalities and has led to increased sensitivity towards soft tissue and peri-neural invasion of tumours leading to upstaging of primary oral cavity malignancies, altering their management. Accuracy is increased when the information of multiple imaging modalities are analysed together and has the potential of changing the management plan of patients.

Prevalence of head and neck cancers in Ahmedabad, Gujarat.

INTRODUCTION: Head and neck cancer constitute one of the commonest cancers in India. Use of smokeless tobacco (pan masala, gutka, zarda, etc.) is the maximum in Gujarat, especially in and around Ahmedabad, and it is responsible for a large majority of these cancers. AIM AND OBJECTIVE: The present study was carried out to study the patient's characteristics, prevalence, treatment modalities and histopathological subtypes of head and neck cancer in and around Ahmedabad. METHODS: A cross-sectional and observational study was carried out at the Head and Neck Services Department of Aastha Oncology Associates, Medi-Surge Hospitals, Ahmedabad, from December 2006 to May 2007. Patients were made to fill up the Case Record Form (CRF) with their informed consent. Proforma of the CRF included patient's age, gender, income, education, family history, lifestyle, signs and symptoms, various investigations, treatment options and adverse effects during treatment and follow up. Preponderance of cancer was found in males (86%) with maximum prevalence in age group 41-60 years (69%). 58% cases were habitual tobacco chewers. Majority of head and neck cancers constituted the tongue, buccal mucosa and alveolus cancers. Radiotherapy and surgery were major treatment options in 44% patients. Blood parameters profile in all the three treatment groups was found to be lower than the control group. CONCLUSION: We conclude that a properly structured and site specific data like this pin points to the magnitude and pattern of head and neck cancer problem in India and it can augment the National Cancer Registry Program.