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.

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.

The Dynamics of Pathology Dataset Creation Using Urine Cytology as an Example

<b><i>Introduction:</i></b> Dataset creation is one of the first tasks required for training AI algorithms but is underestimated in pathology. High-quality data are essential for training algorithms and data should be labelled accurately and include sufficient morphological diversity. The dynamics and challenges of labelling a urine cytology dataset using The Paris System (TPS) criteria are presented. <b><i>Methods:</i></b> 2,454 images were labelled by pathologist consensus via video conferencing over a 14-day period. During the labelling sessions, the dynamics of the labelling process were recorded. Quality assurance images were randomly selected from images labelled in previous sessions within this study and randomly distributed throughout new labelling sessions. To assess the effect of time on the labelling process, the labelled set of images was split into 2 groups according to the median relative label time and the time taken to label images and intersession agreement were assessed. <b><i>Results:</i></b> Labelling sessions ranged from 24 m 11 s to 41 m 06 s in length, with a median of 33 m 47 s. The majority of the 2,454 images were labelled as benign urothelial cells, with atypical and malignant urothelial cells more sparsely represented. The time taken to label individual images ranged from 1 s to 42 s with a median of 2.9 s. Labelling times differed significantly among categories, with the median label time for the atypical urothelial category being 7.2 s, followed by the malignant urothelial category at 3.8 s and the benign urothelial category at 2.9 s. The overall intersession agreement for quality assurance images was substantial. The level of agreement differed among classes of urothelial cells – benign and malignant urothelial cell classes showed almost perfect agreement and the atypical urothelial cell class showed moderate agreement. Image labelling times seemed to speed up, and there was no evidence of worsening of intersession agreement with session time. <b><i>Discussion/Conclusion:</i></b> Important aspects of pathology dataset creation are presented, illustrating the significant resources required for labelling a large dataset. We present evidence that the time taken to categorise urine cytology images varies by diagnosis/class. The known challenges relating to the reproducibility of the AUC (atypical) category in TPS when compared to the NHGUC (benign) or HGUC (malignant) categories is also confirmed.

Case Report: Metachronous bilateral upper tract and bladder urothelial carcinoma: a long-term follow-up

Background: Upper tract urothelial carcinoma (UTUC) is a malignant disease of the urothelial cell lining the upper urinary tract from renal calyces, pelvises, and ureter down to the ureteral orifice. Urothelial carcinoma is a multifocal malignant tumor which tends to reoccur after treatment. Radical cystectomy shows that upper tract recurrence occurs in 0.75% to 6.4% of patients. The occurrence of contralateral UTUC after nephroureterectomy is rarer with a prevalence of 0.5%. Case presentation: The case of a 43-year-old male with metachronous bilateral UTUC was reported. The patient had undergone gemcitabine-cysplatine neoadjuvant chemotherapy followed by radical cystectomy and orthotopic neobladder for urothelial carcinoma of the bladder cT2N0M0. Left hydronephrosis was discovered three months after the procedure. The patient was diagnosed with left UTUC cT4N0M0 of renal pyelum after a series of examinations. A left open radical nephroureterectomy was conducted to remove the mass followed by adjuvant chemotherapy. This was followed up with routine ultrasound and magnetic resonance imaging (MRI) every three months with a “tumor-free” period of 26 months. Meanwhile, the patient was re-admitted with fever and an increase in creatinine value of 4.3. After further workups, the patient was diagnosed with UTUC cT2N0M0 of the right renal pyelum. A kidney sparring approach with laser evaporation of the tumor was conducted followed by eight cycles of Gemcitabine intracavity antegrade per nephrostomy. After the regimen was finished, an MRI evaluation was conducted to assess treatment results, and the mass had decreased. Conclusions: This report showed a rare case of urothelial cell carcinoma recurrences. From bladder urothelial carcinoma to left UTUC and then to contralateral UTUC. It is important to evaluate the upper tract to reduce the risk of recurrence.

Exocyst Inactivation in Urothelial Cells Disrupts Autophagy and Activates non-canonical NF-κB

Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have reported that ureteric bud specific ablation of the exocyst Exoc5 subunit in late murine gestation results in failure of urothelial stratification, cell death, and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death, and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-κB stress response. Impaired autophagy first provokes canonical NF κB activity which is progressively followed by increasing non-canonical NF-κB activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of pan-caspase inhibitor z VAD-FMK at E16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-κB signaling which promotes obstructive uropathy.