Surgical Management of Upper Urinary Tract Urothelial Cell Carcinoma with Venous Tumor Thrombus: A Liver Transplant-Based Approach

Upper urinary tract urothelial cell carcinoma (UTUC) with venous tumor thrombus (TT) that extends into the renal vein (RV) and inferior vena cava (IVC) is a rare entity and its management is a surgical challenge. We report the largest single experience of surgical management of UTUC and accompanying venous TT with radical nephroureterectomy and tumor thrombectomy (RNATT) using transplant-based (TB) surgical techniques. From September 2003 to June 2021, nine patients with UTUC and venous TT underwent RNATT. Demographics, disease characteristics, surgical details, 30-day postoperative complications, and overall survival (OS) were analyzed. All nine patients had extension of the TT into the RV. Of those, seven had additional extension of the TT into the IVC. Venous TT level was categorized as 0 (n = 2), I (n = 2), II (n = 4), and IIIa (n = 1). Median tumor size was 12 cm (range 3–20 cm). Median estimated blood loss was 300 (range 150–1000) cc. One patient was still alive at last follow-up (4 months), and in total, eight patients have died with a median time-to-death of 12 months (range 10 days–24 months). RNATT using TB maneuvers like liver mobilization and pancreas-spleen en bloc mobilization provide excellent exposure to the retroperitoneal space and enable the safe removal of UTUC with venous TT.

Epithelial-to-Mesenchymal Transition Mediates Resistance to Maintenance Therapy with Vinflunine in Advanced Urothelial Cell Carcinoma

In the phase II MAJA trial, maintenance therapy with vinflunine resulted in longer progression-free survival compared to best supportive care in advanced urothelial cell carcinoma (aUCC) patients who did not progress after first-line platinum-based chemotherapy. However, despite an initial benefit observed in some patients, unequivocal resistance appears which underlying mechanisms are presently unknown. We have performed gene expression and functional enrichment analyses to shed light on the discovery of these underlying resistance mechanisms. Differential gene expression profile of eight patients with poor outcome and nine with good outcome to vinflunine administered in the MAJA trial were analyzed. RNA was isolated from tumor tissue and gene expression was assessed by microarray. Differential expression was determined with linear models for microarray data. Gene Set Enrichment Analysis (GSEA) was used for the functional classification of the genes. In vitro functional studies were performed using UCC cell lines. Hierarchical clustering showed a differential gene expression pattern between patients with good and poor outcome to vinflunine treatment. GSEA identified epithelial-to-mesenchymal transition (EMT) as the top negatively enriched hallmark in patients with good outcome. In vitro analyses showed that the polyphenol curcumin downregulated EMT markers and sensitized UCC cells to vinflunine. We conclude that EMT mediates resistance to vinflunine and suggest that the reversion of this process could enhance the effect of vinflunine in aUCC patients.

Urothelial Cell Carcinoma of the Renal Pelvis Misdiagnosed as Ureteropelvic Junction Obstruction: A Case Report

Urothelial tumors are typically a disease affecting elderly individuals and are rare in young patients. Moreover, upper urinary tract urothelial carcinoma is extremely rare in the young age group. In this study, we present a case of urothelial cell carcinoma of the renal pelvis and ureter in a young man without risk factors of urothelial carcinoma, which was misdiagnosed as ureteropelvic junction obstruction and treated with a laparoscopic pyeloplasty.