Oral Metronomic Chemotherapy in Advanced and Metastatic Oral Squamous Cell Carcinoma: A Need of the Hour.

Aim: The present review article aims to compile the best available evidence-based data on oral metronomic chemotherapy (OMCT) including its mechanism of action, its utility, and future directions. Methods: A systematic search was carried out in PubMed database for available English literature from last 10 years between 2011 and 2021. Keyword combinations used were 'Oral Metronomic chemotherapy for oral cancer, mechanism of action of OMCT, Oral metronomic chemotherapy in India, OMCT in recurrent and palliative treatment of oral cancers.' Results: Multitudes of studies have been published recently stating the role of OMCT in head and neck squamous cell carcinoma (HNSCC), but the studies with the category of level of evidence required to advocate OMCT as a recognized therapy are still scarce. On careful stratification of these studies, we found that OMCT has a lot to offer in palliative settings, recurrent, and metastatic HNSCC. There is some limited evidence of its role in adjuvant therapy as maintenance and in neoadjuvant setting. Conclusion: With current evidence, there is a definite role of OMCT in treatment of oral SCC. OMCT can be an alternative in patients who are not tolerable or affordable for standard palliative chemotherapy and also an option for patient who are waiting for surgery. However, results of ongoing and future studies on exact mechanism, indications, and implications of this drug regimen would help in integration OMCT in current standard of therapy.

Expression of PTGS2 along with genes regulating VEGF signalling pathway and association with high-risk factors in locally advanced oral squamous cell carcinoma.

BACKGROUND: PTGS2 encodes cyclooxygenase-2 (COX-2), which catalyses the committed step in prostaglandin synthesis. Various in vivo and in vitro data suggest that COX-2 mediates the VEGF signalling pathway. In silico analysis performed in TCGA, PanCancer Atlas for head and neck cancers, demonstrated significant expression and co-expression of PTGS2 and genes that regulate VEGF signalling. This study was designed to elucidate the expression pattern of PTGS2 and genes regulating VEGF signalling in patients with locally advanced oral squamous cell carcinoma (OSCC). METHODOLOGY: Tumour and normal tissue samples were collected from patients with locally advanced OSCC. RNA was isolated from tissue samples, followed by cDNA synthesis. The cDNA was used for gene expression analysis (RT-PCR) using target-specific primers. The results obtained were compared with the in silico gene expression of the target genes in the TCGA datasets. Co-expression analysis was performed to establish an association between PTGS2 and VEGF signalling genes. RESULTS: Tumour and normal tissue samples were collected from 24 OSCC patients. Significant upregulation of PTGS2 expression was observed. Furthermore, VEGFA, KDR, CXCR1 and CXCR2 were significantly upregulated in tumour samples compared with paired normal samples, except for VEGFB, whose expression was not statistically significant. A similar expression pattern was observed in silico, except for CXCR2 which was highly expressed in the normal samples. Co-expression analysis showed a significant positive correlation between PTGS2 and VEGF signalling genes, except for VEGFB which showed a negative correlation. CONCLUSION: PTGS2 and VEGF signalling genes are upregulated in OSCC, which has a profound impact on clinical outcomes.

Ipsilateral Cervicodeltopectoral Flap: A Forgotten Technique, Revival in the Era of Microvascular Reconstruction.

Oral cavity cancer is one of the most common cancers in India responsible for significant morbidity and mortality in Indian subcontinent. Majority of cases present in advanced stages which requires extensive reconstruction following tumor resection. Microvascular free flap reconstruction is now considered standard of care for reconstruction for major head and neck skin-mucosal defects but, many factors still act as hindrance like patient's comorbidities, long operating hours for microvascular reconstruction, logistic and financial issues from patient's side. In such situation it is better to have a backup plan for reconstruction of major head and neck defects using pedicled flaps. Pectoralis major myocutaneous (PMMC) flap has been the workhorse flap for head and neck reconstruction since its introduction four decades ago. But relying too much on PMMC flap for major skin-mucosal defects especially in female patients is associated with complications and risk for flap failure leading to catastrophic and significant patient morbidities. Our study involves the use of two flaps for head and neck reconstuction involving skin-mucosal defects i.e PMMC flap for mucosal defect and cervicodeltopectoral (CDP) flap for skin defect. As of now there has been no retrospective or prospective study done which has given a conclusive statement regarding use of these two flaps simultaneously for head and neck reconstruction to the best of our knowledge. In our experience from the present study, CDP flap offers an excellent alternative for extensive head and neck reconstruction and can be readily included in the surgeon's armamentarium with proper planning and meticulous handling.

Prostaglandin-endoperoxide synthase 2 (PTGS2) gene expression and its association with genes regulating the VEGF signaling pathway in head and neck squamous cell carcinoma.

Introduction: The PTGS2 gene codes for the cyclooxygenase-2 (COX-2) enzyme that catalyzes the committed step in prostaglandin (PG) synthesis. Various in-vivo and in-vitro data suggest that prostaglandin E2 mediates as a signaling molecule for activating the VEGF signaling pathway (VSP), forming an association between COX-2 and VSP. Several chemotherapy regimens increasingly rely on preventing the synthesis of PGs. The targeted and metronomic chemotherapy agents, which suppress the COX-2 enzymes, have a major role in suppressing the oral cancer cascade. Hence, this study was designed to understand the pattern of PTGS2 expression and genes regulating VSP in head and neck cancers. Methods: PTGS2 expression was analyzed in the TCGA database computationally with the help of the UALCAN web-server. The expression of VEGF signaling pathway genes was mined, and their expression pattern was determined. Co-expression analysis was done to elucidate the association between VEGF signaling genes and PTGS2. The ShineyGo web server was used for gene set enrichment. Results: Significantly high PTGS2 expression was observed in tumor samples. Further genes regulating VEGF signaling were significantly overexpressed in tumor samples. Co-expression analysis results showed a significant positive correlation between PTGS2 and angiogenesis-regulating genes. The majority of the genes were enriched for angiogenesis pathways. Conclusion: PTGS2 was significantly expressed in head and neck cancer, and its expression was associated with genes regulating angiogenesis.

To CT or not to CT: Questioning the Cost-Effectiveness of CT Thorax in Head and Neck Cancers.

Computed tomography (CT) scan has been an integral part of the diagnostic workup for patients with head and neck squamous cell carcinoma. Our study was designed to find out the incidence of distant metastasis and second primary tumor and to correlate the cost-effectiveness of CT thorax in detecting the same. This study was conducted among 326 cancer patients who visited our center with curative intent in the year 2021, with lesions in various head and neck subsites. Data were collected based on their pathological TNM staging and the presence of distant metastasis as evident on their CT thorax imaging with various variables related to the disease. Incremental cost-effectiveness ratio (ICER) was calculated for detecting a single metastatic deposit and second primary tumor in terms of Indian currency and was correlated to each subsite and stage of disease at presentation. Out of these 326 patients, 281 patients were included in our study after considering the inclusion criteria, and among these 281 patients, 235 of them underwent CT thorax for metastatic workup. No patient was found to have a second primary. Metastases were found in 12 patients. The site of primary lesion and clinical tumor (cT) staging were found to be significantly influencing the incidence of metastasis on CT thorax. ICER was least for larynx, pharynx, and paranasal sinuses and was highest for oral cavity primaries and early-stage disease. As per our observations and results of ICER, CT thorax is indeed a valuable modality but should be used judiciously when it comes to initial diagnostic workup.

The contralateral based Cervico-pectoral rotation flap for large neck defects.

PURPOSE: We here describe our technique of contralateral based cervico-pectoral (CCP) flap for the reconstruction of large neck defect following resection of primary tumour or recurrence particularly due to the lymph node mass. METHODS: The study included the patients who underwent major head and neck surgical ablative procedures followed by CCP flap reconstruction between July 2020 and November 2020. Patients were kept on rigorous regular follow-up to evaluate for flap related complications like flap necrosis, flap dehiscence and oro-cutaneous fistula. Among the 5 patients included and presented in the series, 2 patients were salvage cases post adjuvant treatment. RESULTS: Five patients who have undergone head and neck reconstruction using CCP flap were included. No major flap related complications occurred in post-operative period. CONCLUSION: The CCP flap is simple to perform and reproducible and can be added to the armamentarium for the reconstruction of large upper neck defect following resection of primary tumour or recurrence involving the cervical skin in resource limited setting and in contraindication for microvascular reconstruction. Proper planning, meticulous dissection and adequate release or rotation and tension free closure would provide best outcomes.

Ponderous Pleomorphic Adenoma of Parotid Obscuring a Grievous Tumor of the Head and Neck: A Rare Case Report.

We present a rare case of simultaneous occurrence of pleomorphic adenoma of the left parotid gland and squamous cell carcinoma (SCC) of left buccal mucosa in a 59-year-old patient. The synchronous occurrence of these two entities has not been reported in the literature. A PubMed database search did not yield any results for search words involving "Oral Cancer," "Synchronous Oral Cancer and Pleomorphic Adenoma of Parotid gland" and "Oral SCC and Pleomorphic Adenoma of Parotid gland." Furthermore, synchronous development of these two tumors may give rise to diagnostic and ma?nagement conundrums as the parotid growth may be considered to be a nodal metastasis.