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.

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.

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.

Outcomes of exenteration in cT4 and fixed cT3 stage primary rectal adenocarcinoma: a subgroup analysis of consolidation chemotherapy following neoadjuvant concurrent chemoradiotherapy.

PURPOSE: The aim was to evaluate the oncological outcomes and the prognostic factors following pelvic exenteration (PE) in cT4 and fixed cT3 stage primary rectal adenocarcinoma and to study the impact of consolidation chemotherapy following neoadjuvant concurrent chemoradiotherapy (NACRT). METHODS: A retrospective analysis of a prospectively maintained database of PE from 2013 to 2018. RESULTS: Out of 2900 colorectal resections, there were 131 pelvic exenterations that were performed, and 100 of these patients had undergone exenteration for primary rectal adenocarcinoma. Of these 100 patients, there were 81 patients who had received NACRT followed by surgery, 50 of whom who had received consolidation chemotherapy and 31 who had undergone surgery without consolidation chemotherapy. R0 resection was achieved in 90% cases. At a median follow-up of 32 months, 2-year disease free survival was 61.8% and estimated 5-year overall survival was 62%. The incidence of distant metastases was 44% vs. 19% (p = 0.023), and the 2-year distant recurrence-free survival was 58% vs. 89% (p = 0.025), respectively, in the 'consolidation chemotherapy group' and the 'no chemotherapy group'. The poorly differentiated grade of tumours, presence of lympho-vascular-invasion, consolidation chemotherapy, and disease recurrence were all found to affect the survival. CONCLUSION: PE with R0 resection achieves excellent survival rates in cT4 and fixed cT3 stage primary rectal adenocarcinoma. The distant recurrence rate may not be altered by consolidation chemotherapy in the subset of high-risk patients. However, further research on consolidation chemotherapy following NACRT in cT4 and fixed cT3 stage primary rectal adenocarcinoma will give a definite answer in the future.

Urinary reconstruction following total pelvic exenteration for locally advanced rectal cancer: complications and factors affecting outcomes.

INTRODUCTION: Total pelvic exenteration (TPE) for rectal cancers is associated with significant morbidity. We evaluated the complications related to urinary reconstruction following TPE and factors predicting urologic morbidity. METHODS: Retrospective analysis of TPE patients with incontinent urinary diversions between August 2013 and January 2020. RESULTS: One hundred TPE were performed with 96 ileal conduits (IC). Early complications occurred in 10 patients that included uretero-ileal leaks (5%), conduit-related complications (3%), and acute pyelonephritis (3%). Late complications were seen in 26% of patients with uretero-intestinal strictures in 11%. Mortality attributable to urinary complications was seen in 2%. No single factor, including prior radiation, recurrent disease, type of anastomosis, or blood loss, predicted development of urinary morbidity. CONCLUSION: Conduit urinary diversion following TPE is associated with high urinary morbidity rate but low mortality. It can be safely performed even after previous surgeries and radiation by a dedicated colorectal team.

Curative resection for adenocarcinoma of the gastro-esophageal junction following neo-adjuvant chemotherapy-thoraco-abdominal vs. trans-abdominal approach.

PURPOSE: This study compares the short- and long-term outcomes between the left thoraco-abdominal and trans-abdominal approaches for radical resection of adenocarcinoma of the gastro-esophageal junction (GEJ) (Siewert types II and III) following neo-adjuvant chemotherapy. METHODS: A retrospective analysis of a prospectively maintained database of patients from May 2008 to December 2016. Demographic variables, perioperative outcomes, and survival were compared between two approaches. RESULTS: Of the 792 patients, who underwent total/proximal gastrectomy during the specified time interval, 162 had Siewert's type II/III lesions, of which 147 received neoadjuvant chemotherapy and were included in the study. Ninety-two and 55 patients underwent definitive surgery through trans-abdominal and left thoraco-abdominal approach respectively. On baseline endoscopy, 81.8% of patients in the left thoraco-abdominal group had lower esophageal mucosal infiltration as compared to 41.3% in the trans-abdominal group (p < 0.001). Both groups were comparable in terms of duration of surgery, blood loss, complications, severity of complications (Clavien-Dindo grade), duration of hospital stay, R0 resection rate, length of proximal margin, and lymph node yield. At a median follow-up of 24 months, there was no difference in recurrence rate and survival between the groups. CONCLUSION: Both left thoraco-abdominal and trans-abdominal are comparable surgical approaches for tumors involving the GEJ in terms of morbidity, perioperative, and long-term oncological outcomes. In patients with lower esophageal involvement, the left thoraco-abdominal approach is a feasible alternative with no added overall morbidity or mortality and can be preferred especially in cases, where a safe proximal margin and anastomosis is deemed technically challenging.

Distal tracheal resection and reconstruction through right posterolateral thoracotomy.

Many retrospective series have been reported on the outcomes of tracheal resection for adenoid cystic carcinoma. However, demonstration on techniques of surgery and ventilatory management during the procedure are rare. We, herewith demonstrate a surgical video, wherein a distal tracheal resection was performed through right posterolateral thoracotomy.

Minimally Invasive Surgery for Pelvic Exenteration in Primary Colorectal Cancer.

BACKGROUND: Minimally invasive surgery (MIS) for pelvic exenteration is not a well-established technique. The aim was to assess the safety and feasibility of MIS for pelvic exenteration in locally advanced primary colorectal cancer and to compare the perioperative outcomes with open surgery. METHODS: This is a retrospective analysis of patients, who had undergone pelvic exenteration for primary colorectal adenocarcinoma from May 2013 to July 2018. The short-term outcomes like perioperative details and histopathological characteristics were compared between the two groups. RESULTS: MIS was performed in 23 patients and open pelvic exenteration was carried out in 72 patients. The mean operative time was significantly more in the MIS group (640 vs. 432 min, p = 0.00). The intraoperative blood loss (900 vs. 1550 ml, p = 0.00) and the requirement for blood transfusion (170 vs. 250 ml, p = 0.03) was significantly less in the MIS group. The overall morbidity (60% vs. 49%, p = 0.306) was comparable between the two groups. The median length of hospital stay in the MIS group was 11 d, compared to 12 d in the open surgery group, (p = 0.634). The rate of R0 resection (87% vs. 89%, p = 0.668) was comparable between the two groups. CONCLUSION: MIS is feasible and safe for total pelvic exenteration and posterior exenteration in carefully selected locally advanced primary colorectal cancer, when performed by an experienced surgical team in high volume centers. An R0 resection with adequate margin can be achieved with good perioperative outcomes in MIS. Long-term oncological outcomes would require further follow up to confirm.

Pelvic Exenteration with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS + HIPEC) for Rectal Cancer-Case Series with Review of Literature.

Incidence of synchronous peritoneal metastases (PM) in colorectal cancer is approximately 5%, with another 5% of the patients develop metachronous PM. Colorectal PM has been hypothesized to be a loco-regional disease rather than a systemic spread, and cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered as a viable treatment option. Pelvic exenteration is an established treatment option for locally advanced rectal cancer, but it is associated with significant morbidity. However, there are no studies evaluating the role of such procedure probably because the majority consider it as an exclusion criterion. Here, we present our experience with three cases of locally advanced rectal cancer with PM, treated successfully with pelvic exenteration and CRS-HIPEC.

Re-Operative Pancreaticoduodenectomy: Challenges and Outcomes.

BACKGROUND: Tata Memorial Centre (TMC) is a high-volume centre for pancreatic tumour resections. We found a continually increasing referral of pancreatic tumours for re-evaluation for surgery, after an initial unsuccessful attempt at resection. AIM: To evaluate reasons of initial in-operability, the feasibility of re-operative pancreatico-duodenectomy (R-PD) and short- and long-term outcomes after R-PD. METHODS: Data was collected from a prospective database of GI and hepato-pancreato-biliary service, TMC, Mumbai from January 2008 to December 2016. RESULTS: Forty patients with periampullary/pancreatic head tumours were referred to us after exploration. Thirty were planned for re-exploration, of whom 25 patients underwent successful R-PD, either upfront (n = 12) or after neo-adjuvant therapy (n = 13). Twenty were adenocarcinomas, 5 had other histologies. Majority of the patients were deemed inoperable in view of suspected vascular involvement at the time of initial surgery (68%). R0 resection was achieved in 90% of adenocarcinoma cases (n = 18). Postoperative major morbidity was 20% and mortality was 4% (n = 1). The estimated 1-, 2- and 5-year survival for those with adenocarcinoma was 83, 71.2, and 29.9% respectively. CONCLUSION: R-PD is safe and should be performed in experienced centres and can achieve long-term outcomes, comparable to conventional PD. The most common reason for denying resection at initial surgery was suspected or perceived vascular involvement.