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.

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.

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.

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.

Signet ring cell cancer of stomach and gastro-esophageal junction: molecular alterations, stage-stratified treatment approaches, and future challenges.

PURPOSE: There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ. METHODS: A systematic search was carried out in PubMed. Studies available in English related to SRCC of stomach and gastro-esophageal junction were identified and evaluated. RESULTS: This study reviewed the current evidence and provided an insight into the molecular alterations, stage-stratified treatment approaches, and future challenges in the management of SRCC of the stomach and GEJ. Specific therapeutic strategies and personalized multimodal treatment have been recommended based on the tumor characteristics of SRCC. CONCLUSION: Multistage carcinogenesis involving genetic and epigenetic aberrations in SRCC is interlinked with stage-dependent prognosis. Specific therapeutic strategy and personalized multimodal treatment should be followed based on the tumor characteristics of SRCC. Endoscopic resection, radical surgery, and perioperative chemotherapy should be offered in carefully selected patients based on stage and prognostic stratification. Future studies in genetic and molecular analysis, histopathological classification, and options of multimodality treatment will improve the prognosis and oncological outcomes in SRCC of gastric and GEJ.

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.

Polymorphisms of T- cell leukemia 1A gene loci are not related to the development of adjuvant letrozole-induced adverse events in breast cancer.

Letrozole, an aromatase inhibitor (AI), is the first-line adjuvant drug for treating hormone receptor-positive (HR+) breast cancer in postmenopausal women. However, harmful adverse events (AEs) and significant differences in drug response among individuals remain a significant problem in clinical application. Current evidence suggests that the observed individual variation in the treatment outcomes of AI is conferred by genetic variants. Hence, in this study, we examined the association of TCL1A gene polymorphisms with letrozole-induced AEs. The study subjects were postmenopausal HR+ breast cancer patients who were receiving adjuvant letrozole. Genomic DNA was isolated by a routine standard phenol-chloroform method. In total, 198 South Indian patients were genotyped for four single nucleotide polymorphisms (SNPs) in the TCL1A gene loci by the TaqMan allelic discrimination assay using the RT-PCR system. We used the odds ratio and 95% confidence interval to assess the genetic association. Musculoskeletal (MS) AEs and vasomotor symptoms (VMSs) are the most common side effects observed in the study cohort. Among 198 patients, 81 experienced musculoskeletal toxicity, reporting MS-AEs, 57 had VMSs, and 33 of them had both. The most frequently identified polymorphic variants in the patient series were rs11849538 (G), with an allele frequency of about 27.3%, followed by rs7158782-G (27.3%), rs7159713-G (25.8%), and rs2369049-G (22.5%). The genetic association analysis indicated no significant difference in the proportion of TCL1A gene variants between patients with and without AEs on either MS-AEs or VMSs. Though we observed high LD in all patient groups, the inferred haplotypes displayed a non-significant association with letrozole-induced specific AEs. However, the SNP functionality analysis by RegulomeDB provided a 2b rank score for rs7158782, suggesting a potential biological function. Our findings suggest that TCL1A gene polymorphisms may not play any role in the prediction of letrozole-induced AEs in South Indian HR+ breast cancer patients.

Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy.

Lysine-specific demethylase 5B (KDM5B/PLU1/JARID1B) is found to be overexpressed in numerous malignancies, including breast, lung, skin, liver, and prostate cancer. Identification of molecules targeting the KDM5B enzyme could be a potential lead in cancer research. Although many KDM5B inhibitors with promising outcomes have been developed so far, its further application in clinical practice is limited due to toxicity and lack of target specificity. Here, we summarize the significance of targeting KDM5B in anticancer therapy and report the molecular docking studies of some known anti-viral agents, decitabine, entecavir, abacavir, penciclovir, and 3-deazaneplanocin A in the catalytic domain JmjC of KDM5B. These studies show the repurposing potential of identified anti-viral agents in cancer therapy.