How to do it: excision of carotid space tumours in proximity to skull base.

This article along with the descriptive video demonstrates the step-by-step surgical approach for excision of tumours located in carotid space in proximity to skull base. We have described the surgical steps without mandibular osteotomy and also demonstrated the technique to safeguard all neuro-vascular anatomy in the vicinity of the carotid space and skull base.

Periarterial and Sub-adventitial Divestment Along with Triangle Operation and RAMPS for Pancreatic Body Cancer.

BACKGROUND: Locally advanced cancers of the pancreatic body can abut or involve the celiac axis, hepatic artery, or superior mesenteric artery. Recent evidence suggests that these tumors are amenable to surgery after neoadjuvant chemotherapy (Hackert et al., Locally advanced pancreatic cancer: neoadjuvant therapy with FOLFIRINOX results in resectability in 60 % of the patients. Ann Surg 264:457-463, 2016; Rangelova et al., Surgery improves survival after neoadjuvant therapy for borderline and locally advanced pancreatic cancer: a single-institution experience. Ann Surg 273:579-86, 2021). An arterial divestment technique can be used for these cancers to get an R0 clearance, thereby avoiding morbid arterial resections (Miao et al., Arterial divestment instead of resection for locally advanced pancreatic cancer (LAPC). Pancreatology 16:S59, 2016; Habib et al., Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: surgical planning with the "halo sign" and "string sign." Surgery 169(5):1026-1031, 2021; Diener et al., Periarterial divestment in pancreatic cancer surgery. Surgery 169(5):1026-31, 2020). Two techniques are described for arterial divestment. In the periarterial divestment technique, the plane of the dissection is between the tumor and the adventitia (Habib et al., Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: surgical planning with the "halo sign" and "string sign." Surgery 169(5):1026-1031, 2021; Diener et al., Periarterial divestment in pancreatic cancer surgery. Surgery 169(5):1026-31, 2020). In sub-adventitial dissection, the plane of dissection is between the tunica adventitia and the external elastic lamina (Gao et al., Sub-adventitial divestment technique for resecting artery-involved pancreatic cancer: a retrospective cohort study. Langenbecks Arch Surg 406:691-701, 2021). The TRIANGLE operation also is one of the surgical techniques to achieve R0 resection in locally advanced pancreatic cancer (Hackert et al., The TRIANGLE operation: radical surgery after neoadjuvant treatment for advanced pancreatic cancer: a single-arm observational study. HPB Oxford 19:1001-1007, 2017). This multimedia article aims to demonstrate peri-arterial and sub-adventitial divestment techniques as well as the TRIANGLE operation for a locally advanced cancer of the body of the pancreas. The video also highlights the technique of posterior radical antegrade modular pancreato-splenectomy (RAMPS) together with lymph node clearance. PATIENT AND METHODS: A 57-year-old women was detected to have pancreatic body adenocarcinoma with tumor contact of the artery and superior mesenteric artery. After neoadjuvant chemotherapy, she was planned to undergo surgical resection. RESULTS: The surgical technique consisted of peri-arterial and sub-adventitial divestment, the TRIANGLE operation and RAMPS (Fig. 1). The procedure was performed within 240 min and involved blood loss of 250 mL. After the procedure, pancreatic leak (POPF-B), chyle leak and diarrhea developed, which were managed conservatively. The final histopathology showed residual, viable, moderately differentiated adenocarcinoma (ypT2N1M0) with all resection margins free. CONCLUSION: The surgical technique consisting of peri-arterial and sub-adventitial divestment, the TRIANGLE operation and RAMPS helps in R0 resection of locally advanced pancreatic body cancer without any compromise in oncologic outcomes and offers an alternative surgical approach to morbid arterial resection.

Antiapoptotic PON2 expression and its clinical implications in locally advanced oral squamous cell carcinoma.

Locally advanced oral squamous cell carcinoma poses a significant challenge in oncology due to its rising incidence and mortality rates. Despite therapeutic progress, understanding molecular intricacies is essential. This study explored the role of PON2, a multifunctional enzyme implicated in antiapoptotic mechanisms. Aberrant PON2 expression in oral cancers raises questions regarding its involvement in evading programmed cell death and treatment resistance. Patients with locally advanced disease were enrolled, and molecular analyses were undertaken on the collected tumor and normal tissues. Utilizing computational datasets, this study used in silico gene expression analysis, differential gene expression analysis in our patient cohort, survival analysis, and gene set enrichment analysis to unravel role of PON2 in disease prognosis. The results showed elevated PON2 levels in advanced tumor stages, correlating with factors such as tobacco exposure, higher tumor grade, and nodal metastasis. Survival analysis revealed prognostic relevance of PON2, with lower expression linked to extended survival rates. Gene set enrichment analysis identified pathways aiding in cancer metastasis influenced by PON2. This study underscores the significance of PON2 expression as a prognostic marker for oral malignancies, with increased expression associated with advanced disease stages. Understanding the molecular profile of the PON2 gene suggests its potential as a valuable biomarker for the management of cancer.

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.

Myoepithelial Carcinoma of Sinonasal Cavity: Peculiar Diagnosis, Conventional Treatment.

Myoepithelial carcinoma is a morphologically diverse tumor which either arises de novo or from the malignant transformation of its benign counterpart i.e. myoepithelioma. These are relatively lesser known entities and are rarely found in head and neck region. Although rare, their first presentation is usually a painless growing mass as seen in our case presentation as well and are infamous for lymph node recurrence and distant metastasis. Due to their clinical presentation and varied morphology these become tedious to diagnose and pose difficulty for a surgeon when presented at a later date due to their effect on the adjacent vital structures. We report a case of myoepithelial carcinoma in head and neck region arising from the nasal cavity, it's mass effect on the adjacent vital organs and the diagnosis and treatment plan to render the patient free of this tumor, preservation of the vision and keeping the recurrence of the tumor at bay.

Increased Gene Expression of C1orf74 Is Associated with Poor Prognosis in Cervical Cancer.

C1orf74, also known as URCL4, has been reported to have higher expression and be associated with poor prognosis in lung adenocarcinoma patients, and its role in regulation of the EGFR/AKT/mTORC1 pathway has been recently elucidated. In the current study, we used publicly available data and experimental validation of C1orf74 gene expression and its association with prognosis in cervical cancer patients. qRT-PCR was performed using RNA from cervical cancer cell lines and twenty-five cervical cancer patients. Data from TNMplot revealed that mRNA expression of the C1orf74 gene in primary tumor tissues, as well as metastatic tissues from cervical cancer patients, was significantly higher compared to normal cervical tissues. HPV-positive tumors had higher expression of this gene compared to HPV-negative tumors. qPCR analysis also demonstrated higher expression of C1orf74 in HPV-positive cervical cancer cell lines and most cervical cancer patients. The promoter methylation levels of the C1orf74 gene in cervical cancer tissues were lower compared to normal cervical tissues (p < 0.05). Collectively, our study indicates that higher expression of the C1orf74 gene caused by hypomethylation of its promoter is associated with poor overall survival in cervical cancer patients. Thus, C1orf74 is a novel prognostic marker in cervical cancer.

Parietal Peritoneum Interposition Tube Graft as an Autologous Substitute for the Reconstruction of Inferior Vena cava Following Resection of Retroperitoneal Sarcoma.

Complete resection of large retroperitoneal tumors often requires vascular resection and reconstruction, which is frequently performed using prosthetic grafts. We report our experience with inferior vena cava reconstruction utilizing a large peritoneal interposition tube graft performed during en bloc resection of retroperitoneal sarcoma and multiorgan resection. This study aimed to increase the awareness of surgical oncologists about the venous reconstruction technique using a large autologous peritoneal graft. An elderly male presented to our cancer center with a history of persistent abdominal pain. The computed tomography (CT) scan reported a large retroperitoneal mass involving the right kidney and the inferior vena cava (IVC). En bloc tumor resection with right nephrectomy and resection of the IVC extending from just above the bifurcation up to the origin of the renal veins was done. IVC reconstruction was performed using autologous parietal peritoneum tube graft. Harvesting the peritoneum and fashioning a large peritoneal tube graft was challenging. Post-operatively, the patient recovered without any complications and was discharged on oral anticoagulants. The CT scan during the follow-up visit at 6 months revealed that the IVC graft was patent with a good flow. Autologous peritoneal grafts are a safe, valid, and readily available option for venous reconstruction.

How to do it: popliteal lymph node dissection.

Popliteal lymph node metastasis is not very frequent. However, in case of lymph node metastasis in the popliteal fossa, template lymph node dissection needs to be performed. In view of the rarity of this procedure, we aim to describe the stepwise technique of popliteal lymph node dissection.

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.

Agenesis of Dorsal Pancreas and Solid Pseudopapillary Tumor: Ventral Pancreas Preserving Portal Vein Resection and Reconstruction Using a Peritoneal Graft.

A diabetic lady in her 40s was referred to surgical oncologists with epigastric pain associated with vomiting. Computed Tomography (CT) Abdomen with contrast demonstrated a mass arising from the head of the pancreas with the absence of dorsal pancreas, confirmed on magnetic resonance cholangio-pancreatography (MRCP). A core needle biopsy was done, and the tumor was revealed to be a solid pseudopapillary epithelial neoplasm. She underwent sub-total pancreatectomy preserving the duodenum and ventral pancreas as there was adequate free margin; however due to the tumor abutting the anterior wall of the portal vein, it was resected, and reconstruction was done using a peritoneal graft. The patient made a good recovery without any significant post-operative events.

Recurrent Giant Myofibroblastic Sarcoma of Neck in a Teenager: Overcoming Treatment Challenges.

Sarcomas are rare tumors arising from a variety of mesenchymal tissues which are even rarer in head and neck region amounting 1% only of the 5% of sarcomas. About 80% of head and neck sarcomas originate in soft tissue while the remaining 20% arise from bone (Cormier and Pollock in J Clin 54:94-109, 2004). One among the commonly presenting variants of sarcomas in head and neck that our patient was diagnosed with is Low grade myofibroblastic sarcoma (LGMS). These even though uncommon have a predilection for head and neck region particularly the tongue (Mentzel et al. in Am J Surg Pathol 22:1228-38, 1998; Cai et al. in Virchows Arch 463:827-36, 2013; Meng et al. in Chin Med J 120:363-9, 2007; Demarosi et al. in Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 108:248-54, 2009). LGMS was reclassified as a distinct entity by the WHO classification of soft tissue tumors in 2002 (Qiu et al. in Oncol Lett 9:619-25, 2015). Oncological resection is the mainstay of treatment. In case of bulky tumor, resection and reconstruction would be challenging. We report a recurrent LGMS of 15-year-old girl who presented with a ginormous soft tissue swelling in her left neck region which made her day-to-day activities strenuous and made her non ambulatory and the line of treatment executed in order to get her back on feet, healthy & free of the debilitating tumor.

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.

A Mechanistic Review of Methotrexate and Celecoxib as a Potential Metronomic Chemotherapy for Oral Squamous Cell Carcinoma.

The combination of low-dose methotrexate and celecoxib as metronomic chemotherapy (MCT) is a novel therapy, believed to act by modulating the immune response, inhibiting angiogenesis and its cytotoxic action, though the exact mechanism of action is unclear. Clinically, MCT was found to be very effective in delaying tumor progression in patients with head and neck squamous cell carcinoma in both curative and palliative settings. This review was aimed to give a brief insight into the mechanism of action and potential molecular alterations of MCT in the treatment of oral cancers taking into consideration the various in vivo and in vitro studies.

Identification of HOX signatures contributing to oral cancer phenotype.

The role of evolutionarily conserved homeobox-containing HOX genes as transcriptional regulators in the developmental specification of organisms is well known. The contribution of HOX genes involvement in oral cancer phenotype has yet to be fully ascertained. TCGA-HNSC HTSeq-counts and clinical data were retrieved from the GDC portal for oral cavity neoplasms. GEO datasets (GSE72627, GSE30784, GSE37991) were accessed and analyzed using GEO2R. Differential HOX gene expression was profiled using the DESeq2 R package with a log2 fold change cut-off (- 1 and + 1) and Benjamini-Hochberg p-adjusted value at ≤ 0.01. Gene set over-representation analysis and semantic analysis associated with the disease ontology was performed using the ClusterProfiler R package, and pathway over-representation analysis was performed using IMPaLa. HOX protein interaction network was constructed using the Pathfind R package. HOX phenotype associations were performed using Mammalian Phenotype Ontology, Human Phenotype Ontology, PhenGenI associations, Jensen tissues, and OMIM entries. Drug connectivity mapping was carried out with Dr. Insight R package. HOXA2 was upregulated in oral dysplasia but silenced during tumor progression. Loss of HOXB2 expression was consistent in the potentially malignant oral lesions as well as in the primary tumor. HOXA7, HOXA10, HOXB7, HOXC6, HOXC10, HOXD10, and HOXD11 were consistently upregulated from premalignancy to malignancy and were notably associated with risk factors. Overrepresentation analysis suggested HOXA10 was involved in the transcriptional misregulation contributing to the oral cancer phenotype. HOX genes subnetwork analysis showed crucial interactions with cell cycle regulators, growth responsive elements, and proto-oncogenes. Phenotype associations specific to the oral region involving HOX genes provide intrinsic cues to tumor development. The 5' HOX genes were aberrantly upregulated during oral carcinogenesis reflecting their posterior prevalence.