Primary hyperoxaluria type 1: urologic and therapeutic management.

While the surgical approaches available in primary hyperoxaluria (PH) are common to all patients requiring intervention for urolithiasis, the indications for treatment and their corresponding toxicities are unique. Being a rare disease, we are guided by case series. This review summarizes the available literature highlighting the important disease-specific considerations. Shockwave lithotripsy (SWL) is of particular interest. It is generally the first-line treatment for stones in children, but here the stones produced will be relatively resistant to fragmentation. In addition, there are concerning reports in children of sudden unilateral decline in function in the treated kidney as measured by nuclear renography. Percutaneous nephrostolithotomy might intuitively seem favorable given the shortest drain duration and the ability to treat larger stones efficiently but, similar to SWL, rapid chronic kidney disease (CKD) progression has been seen postoperatively. Ureteroscopy is therefore generally the safest option, but considerations regarding stent encrustation, the growth of residual fragments and the large volume of stone often faced may limit this approach. The surgeon must balance the above with consideration of the patient's CKD status when considering a plan of monitoring and treating stones in PH.

Differential expression of miRNAs involved in biological processes responsible for inflammation and immune response in lichen sclerosus urethral stricture disease.

PURPOSE: To better understand the pathophysiology of lichen sclerosus (LS) urethral stricture disease (USD), we aimed to investigate expression profiles of microRNAs (miRNAs) in tissue samples from men undergoing urethroplasty. METHODS: Urethral stricture tissue was collected from 2005-2020. Histologic features diagnostic of LS were the basis of pathologic evaluation. Foci of areas diagnostic for LS or non-LS strictures were chosen for RNA evaluation. In an initial screening analysis, 13 LS urethral strictures and 13 non-LS strictures were profiled via miRNA RT-qPCR arrays for 752 unique miRNA. A validation analysis of 23 additional samples (9 LS and 14 non-LS) was performed for 15 miRNAs. Statistical analyses were performed using SPSS v25. Gene Ontology (GO) analysis was performed using DIANA-mirPath v. 3.0. RESULTS: In the screening analysis 143 miRNAs were detected for all samples. 27 were differentially expressed between the groups (false discovery p-value <0.01). 15 of these miRNAs individually demonstrated an area under the curve (AUC)>0.90 for distinguishing between between LS and non-LS strictures. 11-fold upregulation of MiR-155-5p specifically was found in LS vs. non-LS strictures (p<0.001, AUC = 1.0). In the validation analysis, 13 of the 15 miRNAs tested were confirmed to have differential expression (false discovery p-value <0.10). CONCLUSIONS: To our knowledge this is the first study evaluating miRNA expression profiles in LS and non-LS USD. We identified several miRNAs that are differentially expressed in USD caused by LS vs other etiologies, which could potentially serve as biomarkers of LS USD. The top eight differentially expressed miRNAs have been linked to immune response processes as well as involvement in wound healing, primarily angiogenesis and fibrosis.

Ureteral Stent Fracture After Irreversible Electroporation for Treatment of Metastatic Rectal Adenocarcinoma.

Background: Irreversible electroporation (IRE) is a soft tissue ablation technique using electrical pulses without thermal energy to create pores in the cell membrane, resulting in death from apoptosis rather than necrosis. Advantages include protection of blood vessels, nerves, and surrounding structures. Documented complications include periprocedure nausea/vomiting, infection, and severe pain. Ureteral stents are frequently used in management of hydronephrosis caused by malignant obstruction. We describe what is to our knowledge the first documentation of stent fragmentation secondary to IRE and subsequent management. Case Presentation: This is a 61-year-old male with history of metastatic rectal adenocarcinoma treated initially with chemotherapy and surgery. Follow-up imaging revealed hydronephrosis and enlarged right iliac lymph node. Ureteral stent was placed for management of the hydronephrosis and the patient was referred to undergo IRE for management of metastatic disease. After treatment, the patient had imaging performed that showed fractured right ureteral stent with proximal portion in the ureter and distal portion floating freely in the bladder. This complication was managed with staged endoscopic procedure involving adjacent ureteral stent placement and subsequent ureteroscopy and stent removal using delta grasper. Conclusion: We describe to our knowledge the first incidence as well as subsequent management of ureteral stent fracture from an increasingly common treatment modality for metastatic disease. Given the frequency of malignant ureteral obstruction managed with ureteral stents, knowledge of potential complications pertaining to the urologist is imperative.

Radiographic Misdiagnoses After Periurethral Bulking Agents.

OBJECTIVES: Injectable urethral bulking agents are commonly used to manage stress urinary incontinence. Urologic or other symptoms may prompt pelvic imaging at a later date, when bulking agents may be visualized and incorrectly interpreted. Our goal was to evaluate the incidence of misdiagnosis and which pathologies were the most common misinterpretations and their frequency. METHODS: All records were reviewed for patients who underwent periurethral injection for stress urinary incontinence for pelvic imaging after treatment from 2005 to 2015. Radiological reports were reviewed for any description potentially related to injection therapy, and descriptive statistics performed. RESULTS: A total of 528 patients underwent injection of a urethral bulking agent. Of these, 79 patients (15%) had a total of 111 additional abdominal or pelvic imaging studies performed with abnormal periurethral findings mentioned. Thirty-nine (35%) of 111 studies were correctly interpreted as urethral bulking agents, and in 72 (65%) of 111 studies, the urethral bulking agents were not correctly identified. The most common misdiagnoses were bladder calcification (26; 23%), urethral diverticulum with stone (12; 11%), periurethral calcification (9; 8%), unknown pelvic density (8; 7%), and mass suspicious for malignancy (6; 5%). CONCLUSIONS: Urethral bulking agents commonly were not mentioned on subsequent imaging but, when commented on, were misinterpreted 65% of the time including worrisome pathologies (diverticulum with stone, unknown mass, and malignancy), requiring subsequent evaluation and potentially procedural/surgical management. It is critical for the ordering clinician to inform the radiologist of this history and for radiologists to consider bulking agents in the differential diagnosis of radiographic findings in this location.

Regulation of the Chlamydomonas cell cycle by a stable, chromatin-associated retinoblastoma tumor suppressor complex.

We examined the cell cycle dynamics of the retinoblastoma (RB) protein complex in the unicellular alga Chlamydomonas reinhardtii that has single homologs for each subunit-RB, E2F, and DP. We found that Chlamydomonas RB (encoded by MAT3) is a cell cycle-regulated phosphoprotein, that E2F1-DP1 can bind to a consensus E2F site, and that all three proteins interact in vivo to form a complex that can be quantitatively immunopurified. Yeast two-hybrid assays revealed the formation of a ternary complex between MAT3, DP1, and E2F1 that requires a C-terminal motif in E2F1 analogous to the RB binding domain of plant and animal E2Fs. We examined the abundance of MAT3/RB and E2F1-DP1 in highly synchronous cultures and found that they are synthesized and remain stably associated throughout the cell cycle with no detectable fraction of free E2F1-DP1. Consistent with their stable association, MAT3/RB and DP1 are constitutively nuclear, and MAT3/RB does not require DP1-E2F1 for nuclear localization. In the nucleus, MAT3/RB remains bound to chromatin throughout the cell cycle, and its chromatin binding is mediated through E2F1-DP1. Together, our data show that E2F-DP complexes can regulate the cell cycle without dissociation of their RB-related subunit and that other changes may be sufficient to convert RB-E2F-DP from a cell cycle repressor to an activator.