While most cases of cutaneous squamous cell carcinoma (cSCC) are benign, invasive cSCC is associated with higher mortality and is often more difficult to treat. As such, understanding the factors that influence the progression of cSCC are important. Aggressive cancers metastasize through a series of evolutionary changes, collectively called the epithelial-to-mesenchymal transition (EMT). During EMT, epithelial cells transition to a highly mobile mesenchymal cell type with metastatic capacities. While changes in expression of TGF-β, ZEB1, SNAI1, MMPs, vimentin, and E-cadherin are hallmarks of an EMT process occurring within cancer cells, including cSCC cells, EMT within tissues is not an “all or none” process. Using patient-derived cSCC and adjacent normal tissues, we show that cells within individual cSCC tumors are undergoing a hybrid EMT process, where there is variation in expression of EMT markers by cells within a tumor mass that may be facilitating invasion. Interestingly, cells along the outer edges of a tumor mass exhibit a more mesenchymal phenotype, with reduced E-cadherin, β-catenin, and cytokeratin expression and increased vimentin expression. Conversely, cells in the center of a tumor mass retain a higher expression of the epithelial markers E-cadherin and cytokeratin and little to no expression of vimentin, a mesenchymal marker. We also detected inverse expression changes in the miR-200 family and the EMT-associated transcription factors ZEB1 and SNAI1, suggesting that cSCC EMT dynamics are regulated in a miRNA-dependent manner. These novel findings in cSCC tumors provide evidence of phenotypic plasticity of the EMT process occurring within patient tissues, and extend the characterization of a hybrid EMT program occurring within a tumor mass. This hybrid EMT program may be promoting both survival and invasiveness of the tumors. A better understanding of this hybrid EMT process may influence therapeutic strategies in more invasive disease.
_______________________________________________________________________________________Background: Inferior vena cava (IVC) invasion from renal cell carcinoma (RCC) occurs at a rate of 4-10% (1). IVC thrombectomy (IVC-TE) can be an open procedure because of the need for handling of the IVC (2). The first reported series of robotic management of IVC-TE started in 2011 for the management of Level I -II thrombi with subsequent case reports in recent years (2-5). Materials and Methods:The following is a patient in his 50's with no significant medical history. Magnetic resonance imaging and IR venogram were performed preoperatively. The tumor was clinical stage T3b with a 4.3cm inferior vena cava thrombus. The patient underwent robotic assisted nephrectomy and IVC-TE. Rummel tourniquets were used for the contralateral kidney and the IVC. The tourniquets were created using vessel loops, a 24 French foley catheter and hem-o-lock clips. Results: The patient tolerated the surgical procedure well with no intraoperative complications. Total surgical time was 274 min with 200 minutes of console time and 22 minutes of IVC occlusion. Total blood loss in the surgery was 850cc. The patient was discharged from the hospital on post-operative day 3 without any complications. The final pathology of the specimen was pT3b clear cell renal cell carcinoma Fuhrman grade 2. The patient followed up post-operatively at both four months and six months without disease recurrence. The patient continues annual follow-up with no recurrence. Conclusions: Surgeon experience is a key factor in radical nephrectomy with thrombectomy as patients have a reported 50-65% survival rate after IVC-TE (4). ABBREVIATIONS IVC = Inferior vena cava RCC = renal cell carcinoma IVC-TE = IVC thrombectomy IR = interventional radiology AUTHOR DISCLOSURE STATEMENTAuthors have received and archived patient consent for video recording/publication in advance of video recording procedure.
Background: High risk upper tract urothelial carcinoma (UTUC) is typically managed with radical nephroureterectomy, however, renal preservation can be attempted when UTUC is localized to the distal ureter in the presence of chronic kidney disease ( 1 – 3 ). Distal ureterectomy is typically managed with a ureteral reimplantation and psoas hitch in order to maintain urothelial continuity, to avoid comprising the contralateral ureter, and reducing risk of chronic urinary tract infections and electrolyte abnormalities ( 4 ). We present our case of distal ureteral UTUC managed robotically with a distal ureterectomy with ureteral reimplantation. Technique and Follow-Up: Initially, an Orandi needle on a resectoscope circumscribed the left ureteral orifice. Next, robotically, the retroperitoneum was exposed and a left sided pelvic lymphadenectomy was completed. The left ureter was mobilized and the diseased ureteral segment was transected. The mobilized bladder was sutured to psoas fascia. After a cystotomy, the ureter was re-anastomosed to the bladder. The patient was discharged on postoperative day three and re-evaluated one week later with a cystogram. Final pathology was downgraded to non-invasive low-grade papillary urothelial carcinoma with negative lymph nodes and margins. Conclusion: High risk UTUC localized to the distal ureter in the setting of chronic kidney disease can be managed with a distal ureterectomy ( 3 ). Robotic distal ureterectomy with ureteral reimplantation can be assisted by an Orandi needle to achieve negative margins. Utilizing a robotic technique can offer challenges with the ureteral spatulation and reanastomosis ( 5 – 7 ). By fixating the ureter to the bladder prior to reanastomosis, our technique offers a solution for these difficulties.
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