Genomic Evolution of Oligometastatic Clear Cell Renal Cell Carcinoma Presenting Two Decades Following Radical Nephrectomy.

Metachronous oligometastatic clear cell renal cell carcinoma may take many years before becoming clinically apparent. Herein we report regional lymph node recurrence of clear cell renal cell carcinoma more than two decades following radical nephrectomy. Chromosomal microarray analysis demonstrated multiple chromosomal alterations, including 3pq deletion shared by the original and recurrent tumors, and 17p deletion containing the TP53 gene present only in the latter. Sequencing of 1550 genes revealed mutations of VHL in both the primary and metastasis and BAP1 only in the metastatic lesion. These findings genetically link the original and recurrent tumors and suggest that VHL, TP53, and BAP1 alterations played an evolutionary role in recurrence decades after initial resection.

Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease.

The fight against hand, foot, and mouth disease (HFMD) remains an arduous challenge without existing point-of-care (POC) diagnostic platforms for accurate diagnosis and prompt case quarantine. Hence, the purpose of this salivary biomarker discovery study is to set the fundamentals for the realization of POC diagnostics for HFMD. Whole salivary proteome profiling was performed on the saliva obtained from children with HFMD and healthy children, using a reductive dimethylation chemical labeling method coupled with high-resolution mass spectrometry-based quantitative proteomics technology. We identified 19 upregulated (fold change = 1.5-5.8) and 51 downregulated proteins (fold change = 0.1-0.6) in the saliva samples of HFMD patients in comparison to that of healthy volunteers. Four upregulated protein candidates were selected for dot blot-based validation assay, based on novelty as biomarkers and exclusions in oral diseases and cancers. Salivary legumain was validated in the Singapore (n = 43 healthy, 28 HFMD cases) and Taiwan (n = 60 healthy, 47 HFMD cases) cohorts with an area under the receiver operating characteristic curve of 0.7583 and 0.8028, respectively. This study demonstrates the feasibility of a broad-spectrum HFMD POC diagnostic test based on legumain, a virus-specific host systemic signature, in saliva.

The essential role of the ERK activation in large T antigen of BK polyomavirus regulated cell migration.

Recent studies have suggested that BK polyomavirus (BKPyV) may be associated with the development of urothelial carcinoma. In Merkel cell carcinoma, TAg and tAg are the major viral proteins of Merkel cell polyomavirus with oncogenic potential. In this study, we aimed to distinguish the role of TAg and tAg in cell migration. Our result demonstrated that ERK was phosphorylated in human renal tubular cells expressing its TAg and tAg after BKPyV infection. Treatment with the ERK inhibitor U0126 suppressed BKPyV gene expression and reduced BKPyV replication. Both TAg and tAg induced cell migration via ERK-dependent signaling. Furthermore, the expression of TAg and tAg had a significant regulatory effect on focal adhesion molecules in renal proximal tubular cells, which strongly suggests that alterations in the focal adhesion complexes are critically involved in TAg and tAg-induced cell migration. Gelatin zymography profiling revealed that TAg regulates the expression and activity of MMP-2 and MMP-9, but not tAg. Interestingly, TAg regulates the expression and activity of MMP-9 through ERK signaling, whereas MMP-2 is regulated through an ERK-independent pathway. Unbalanced ERK pathway activity is frequently observed in many cancers, while MMP proteins are usually overexpressed in aggressive tumors. These findings support the view that BKPyV is an oncogenic virus.

TEQUILA-seq: a versatile and low-cost method for targeted long-read RNA sequencing.

Long-read RNA sequencing (RNA-seq) is a powerful technology for transcriptome analysis, but the relatively low throughput of current long-read sequencing platforms limits transcript coverage. One strategy for overcoming this bottleneck is targeted long-read RNA-seq for preselected gene panels. We present TEQUILA-seq, a versatile, easy-to-implement, and low-cost method for targeted long-read RNA-seq utilizing isothermally linear-amplified capture probes. When performed on the Oxford nanopore platform with multiple gene panels of varying sizes, TEQUILA-seq consistently and substantially enriches transcript coverage while preserving transcript quantification. We profile full-length transcript isoforms of 468 actionable cancer genes across 40 representative breast cancer cell lines. We identify transcript isoforms enriched in specific subtypes and discover novel transcript isoforms in extensively studied cancer genes such as TP53. Among cancer genes, tumor suppressor genes (TSGs) are significantly enriched for aberrant transcript isoforms targeted for degradation via mRNA nonsense-mediated decay, revealing a common RNA-associated mechanism for TSG inactivation. TEQUILA-seq reduces the per-reaction cost of targeted capture by 2-3 orders of magnitude, as compared to a standard commercial solution. TEQUILA-seq can be broadly used for targeted sequencing of full-length transcripts in diverse biomedical research settings.

Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.

Asymptomatic Necrotizing Granulomatous Disease of the Neck With Unknown Etiology.

Patients presenting with unilateral neck masses is not an uncommon occurrence in an otolaryngology clinic. Especially those with risk factors such as older age and a history of smoking or drinking along with certain characteristics of the mass including rapid growth, immobility, and the presence of other masses elsewhere in the head and neck that can lead to more concerning etiologies such as cancer. However, in those who are younger with non-tender unilateral mobile masses, the differential is wide. We present the case of a 30-year-old male who presented with a non-tender left-sided neck mass with no associated or systemic symptoms. Workup including labs for HIV, syphilis, and fungal stains was negative. Pathology demonstrated lymphadenitis with necrotizing granulomas with no recurrence of symptoms after excisional biopsy. The patient continued to have no associated symptoms or recurrent mass thus no further workup was deemed necessary. Although unilateral neck mass and lymphadenitis with necrotizing lymphadenitis have a broad differential diagnosis, this patient's etiology continues to be unknown.

IRIS: Discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing.

Alternative splicing (AS) is prevalent in cancer, generating an extensive but largely unexplored repertoire of novel immunotherapy targets. We describe Isoform peptides from RNA splicing for Immunotherapy target Screening (IRIS), a computational platform capable of discovering AS-derived tumor antigens (TAs) for T cell receptor (TCR) and chimeric antigen receptor T cell (CAR-T) therapies. IRIS leverages large-scale tumor and normal transcriptome data and incorporates multiple screening approaches to discover AS-derived TAs with tumor-associated or tumor-specific expression. In a proof-of-concept analysis integrating transcriptomics and immunopeptidomics data, we showed that hundreds of IRIS-predicted TCR targets are presented by human leukocyte antigen (HLA) molecules. We applied IRIS to RNA-seq data of neuroendocrine prostate cancer (NEPC). From 2,939 NEPC-associated AS events, IRIS predicted 1,651 epitopes from 808 events as potential TCR targets for two common HLA types (A*02:01 and A*03:01). A more stringent screening test prioritized 48 epitopes from 20 events with "neoantigen-like" NEPC-specific expression. Predicted epitopes are often encoded by microexons of ≤30 nucleotides. To validate the immunogenicity and T cell recognition of IRIS-predicted TCR epitopes, we performed in vitro T cell priming in combination with single-cell TCR sequencing. Seven TCRs transduced into human peripheral blood mononuclear cells (PBMCs) showed high activity against individual IRIS-predicted epitopes, providing strong evidence of isolated TCRs reactive to AS-derived peptides. One selected TCR showed efficient cytotoxicity against target cells expressing the target peptide. Our study illustrates the contribution of AS to the TA repertoire of cancer cells and demonstrates the utility of IRIS for discovering AS-derived TAs and expanding cancer immunotherapies.

Current Status and Future Direction to Address Disparities in Diversity, Equity, and Inclusion in Prostate Cancer Care.

PURPOSE OF REVIEW: Disparities in prostate cancer care and outcomes have been well recognized for decades. The purpose of this review is to methodically highlight known racial disparities in the care of prostate cancer patients, and in doing so, recognize potential strategies for overcoming these disparities moving forward. RECENT FINDINGS: Over the past few years, there has been a growing recognition and push towards addressing disparities in cancer care. This has led to improvements in care delivery trends and a narrowing of racial outcome disparities, but as we highlight in the following review, there is more to be addressed before we can fully close the gap in prostate cancer care delivery. While disparities in prostate cancer care are well recognized in the literature, they are not insurmountable, and progress has been made in identifying areas for improvement and potential strategies for closing the care gap.

Intra-practice Urologist-level Variation in Targeted Fusion Biopsy Outcomes.

OBJECTIVE: To examine the extent to which the urologist performing biopsy contributes to variation in prostate cancer detection during fusion-guided prostate biopsy. METHODS: All men in the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry who underwent fusion biopsy at Michigan Medicine from August 2017 to March 2019 were included. The primary outcomes were clinically significant cancer detection rate (defined as Gleason Grade ≥2) in targeted cores and clinically significant cancer detection on targeted cores stratified by PI-RADS score. Bivariate and multivariable logistic regression analyses were performed. RESULTS: A total of 1133 fusion biopsies performed by 5 providers were included. When adjusting for patient age, PSA, race, family history, prostate volume, clinical stage, and PI-RADS score, there was no significant difference in targeted clinically significant cancer detection rates across providers (range = 38.5%-46.9%, adjusted P-value = .575). Clinically significant cancer detection rates ranged from 11.1% to 16.7% in PI-RADS 3 (unadjusted P = .838), from 24.6% to 43.4% in PI-RADS 4 (adjusted P = .003), and from 69.4% to 78.8% in PI-RADS 5 (adjusted P = .766) lesions. CONCLUSION: There was a statistically significant difference in clinically significant prostate cancer detection in PI-RADS 4 lesions across providers. These findings suggest that even among experienced providers, variation at the urologist level may contribute to differences in clinically significant cancer detection rates within PI-RADS 4 lesions. However, the relative impact of biopsy technique, radiologist interpretation, and MR acquisition protocol requires further study.

Base of Tongue Squamous Cell Carcinoma With Metastasis to the Mandibular Symphysis: A Case Report.

Squamous cell carcinoma (SCC) is the most common malignancy of the oropharynx (OP). Treatment of OP SCC includes chemotherapy, radiation, and/or surgery. OP SCC can spread via direct extension, lymphatics, or hematogenously. Although rare, distant metastases can occur in OP SCC. The most common sites of metastasis include the lungs, bone, and liver. Other less common sites include the skin, bone marrow, brain, kidneys, eyes, and heart. Patients who present with distant metastases usually have a poor prognosis. Sites of bone metastases from more common to less common include the spine, skull, ribs, and axial bones. In this article, we discuss a patient who presents with HPV+ base of tongue SCC with metastases to the lungs and mandible symphysis. Base of tongue SCC metastasizing to the mandible symphysis is a rarely reported location of metastasis.

Cowden Syndrome Case Report: Use of an Ultrasonic Surgical Aspirator for Cosmetic Removal of Lip Hamartomas.

Cowden syndrome (CS) is an autosomal dominant condition that is relatively rare. CS patients can have tumors derived from all three germlines. They can present with mucocutaneous hamartomas or other benign tumors, and have an increased risk of malignancies of the thyroid, breast, kidney, GI tract, and skin. In our clinic, a 40-year-old CS patient presented for thyroidectomy after fine needle aspiration was suspicious for papillary thyroid carcinoma (PTC). Another major concern was the cosmetic appearance of her lips, which were diffusely covered with small hamartomas. We were able to remove these in a novel manner using a cavitron ultrasonic surgical aspirator (CUSA; Integra Lifesciences, Princeton, NJ, USA). Using the CUSA tangential to the lip surface allowed for removal of the hamartomas in a way that created a smooth and cosmetically appealing outcome for the patient. The use of an ultrasonic surgical aspirator is a novel way to cosmetically treat hamartomas of the lip for CS patients.

E. coli 6S RNA complexed to RNA polymerase maintains product RNA synthesis at low cellular ATP levels by initiation with noncanonical initiator nucleotides.

The E. coli 6S RNA is an RNA polymerase (RNAP) inhibitor that competes with σ70-dependent DNA promoters for binding to RNAP holoenzyme (RNAP:σ70). The 6S RNA when bound is then used as a template to synthesize a short product RNA (pRNA; usually 13-nt-long). This pRNA changes the 6S RNA structure, triggering the 6S RNA:pRNA complex to release and allowing DNA-dependent housekeeping gene expression to resume. In high nutrient conditions, 6S RNA turnover is extremely rapid but becomes very slow in low nutrient environments. This leads to a large accumulation of inhibited RNAP:σ70 in stationary phase. As pRNA initiates synthesis with ATP, we and others have proposed that the 6S RNA release rate strongly depends on ATP levels as a proxy for sensing the cellular metabolic state. By purifying endogenous 6S RNA:pRNA complexes using RNA Mango and using reverse transcriptase to generate pRNA-cDNA chimeras, we demonstrate that 6S RNA:pRNA formation can be simultaneous with 6S RNA 5' maturation. More importantly, we find a dramatic accumulation of capped pRNAs during stationary phase. This indicates that ATP levels in stationary phase are low enough for noncanonical initiator nucleotides (NCINs) such as NAD+ and NADH to initiate pRNA synthesis. In vitro, mutation of the conserved 6S RNA template sequence immediately upstream of the pRNA transcriptional start site can increase or decrease the pRNA capping efficiency, suggesting that evolution has tuned the biological 6S RNA sequence for an optimal capping rate. NCIN-initiated pRNA synthesis may therefore be essential for cell viability in low nutrient conditions.

Mechanism of Oil-in-Liquid Metal Emulsion Formation.

Gallium-based liquid metals (LMs) combine metallic properties with the deformability of a liquid, which makes them promising candidates for a variety of applications. To broaden the range of physical and chemical properties, a variety of solid additives have been incorporated into the LMs in the literature. In contrast, only a handful of secondary fluids have been incorporated into LMs to create foams (gas-in-LM) or emulsions (liquid-in-LM). LM foams readily form through mixing of LM in air, facilitated by the formation of a native oxide on the LM. In contrast, LM breaks up into microdroplets when mixed with a secondary liquid such as silicone oil. Stable silicone oil-in-LM emulsions form only during mixing of the oil with LM foam. In this work, we investigate the fundamental mechanism underlying this process. We describe two possible microscale mechanisms for emulsion formation: (1) oil replacing air in the foam or (2) oil creating additional features in the foam. The associated foam-to-emulsion density difference demonstrates that emulsions predominantly form through the addition of oxide-covered silicone oil capsules to the LM foam. We demonstrate this through density and surface wettability measurements and multiscale imaging of LM foam mixed with varied silicone oil contents in air or nitrogen environments. We also demonstrate the presence of a continuous silicone oil film on the emulsion surface and that this oil film prevents the embrittlement of contacting aluminum.

Measurements of Anti-SARS-CoV-2 Antibody Levels after Vaccination Using a SH-SAW Biosensor.

To prevent the COVID-19 pandemic that threatens human health, vaccination has become a useful and necessary tool in the response to the pandemic. The vaccine not only induces antibodies in the body, but may also cause adverse effects such as fatigue, muscle pain, blood clots, and myocarditis, especially in patients with chronic disease. To reduce unnecessary vaccinations, it is becoming increasingly important to monitor the amount of anti-SARS-CoV-2 S protein antibodies prior to vaccination. A novel SH-SAW biosensor, coated with SARS-CoV-2 spike protein, can help quantify the amount of anti-SARS-CoV-2 S protein antibodies with 5 µL of finger blood within 40 s. The LoD of the spike-protein-coated SAW biosensor was determined to be 41.91 BAU/mL, and the cut-off point was determined to be 50 BAU/mL (Youden's J statistic = 0.94733). By using the SH-SAW biosensor, we found that the total anti-SARS-CoV-2 S protein antibody concentrations spiked 10−14 days after the first vaccination (p = 0.0002) and 7−9 days after the second vaccination (p = 0.0116). Furthermore, mRNA vaccines, such as Moderna or BNT, could achieve higher concentrations of total anti-SARS-CoV-2 S protein antibodies compared with adenovirus vaccine, AZ (p < 0.0001). SH-SAW sensors in vitro diagnostic systems are a simple and powerful technology to investigate the local prevalence of COVID-19.

Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein.

Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many studies have reported its antiviral and anti-inflammatory activities. However, the high cytotoxicity and very low solubility of Cur limit its biomedical applications. In this study, Cur carbon quantum dots (Cur-CQDs) were synthesized by mild pyrolysis-induced polymerization and carbonization, leading to higher water solubility and lower cytotoxicity, as well as superior antiviral activity against JEV infection. We found that Cur-CQDs effectively bound to the E protein of JEV, preventing viral entry into the host cells. In addition, after continued treatment of JEV with Cur-CQDs, a mutant strain of JEV was evolved that did not support binding of Cur-CQDs to the JEV envelope. Using transmission electron microscopy, biolayer interferometry, and molecular docking analysis, we revealed that the S123R and K312R mutations in the E protein play a key role in binding Cur-CQDs. The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections.

Extension study of the safety and efficacy of CLS-TA for treatment of macular oedema associated with non-infectious uveitis (MAGNOLIA).

PURPOSE: To assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU). METHODS: Patients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control). RESULTS: Over the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed. CONCLUSION: Approximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration.

Suprachoroidal CLS-TA for non-infectious uveitis: an open-label, safety trial (AZALEA).

PURPOSE: To evaluate local and systemic safety of suprachoroidal (SC) triamcinolone acetonide injectable suspension (CLS-TA) injections in subjects with non-infectious uveitis (NIU). DESIGN: Open-label, prospective multicentre safety study. PARTICIPANTS: Thirty-eight subjects with NIU, with and without macular oedema (MO). METHODS: Treatment consisted of two suprachoroidal injections of CLS-TA 4 mg, 12 weeks apart. Best-corrected visual acuity (BCVA), adverse event (AE) assessment, ophthalmic examinations and optical coherence tomography (OCT) were conducted every 4 weeks for 24 weeks. Blood samples were analysed for plasma triamcinolone acetonide (TA) concentrations. MAIN OUTCOME MEASURES: The main outcome measure was frequency of AEs. Other endpoints included plasma TA concentrations, change in signs of inflammation, BCVA and retinal central subfield thickness (CST). RESULTS: Based on a CST of >300 µm, 20 out of 38 subjects had MO at baseline. Mean intraocular pressure (IOP) was 13.3 mm Hg at baseline and 15.2 mm Hg at week 24 in the study eye. A total of six (15.8%) subjects had an IOP rise >10 mm Hg compared with baseline, in the study eye, and two (5.3%) subjects had IOP >30 mm Hg (maximum 34 mm Hg at week 8 and 38 mm Hg at week 20). Cataract formation AEs were reported in four study eyes; one of which was deemed treatment-related. No serious ocular AEs in the study eye occurred in the study. Quantifiable post-injection TA plasma concentration was <1 ng/mL. Efficacy parameters showed improvement over the 24-week study period. CONCLUSIONS: Suprachoroidally administered CLS-TA was safe and well tolerated over the 24-week, open-label study in NIU subjects with and without MO.

Gallium oxide-stabilized oil in liquid metal emulsions.

Gallium based liquid metals (LM) have prospective biomedical, stretchable electronics, soft robotics, and energy storage applications, and are being widely adopted as thermal interface materials. The danger of gallium corroding most metals used in microelectronics requires the cumbersome addition of "barrier" layers or LM break-up into droplets within an inert matrix such as silicone oil. Such LM-in-oil emulsions are stabilized by native oxide on the droplets but have decreased thermal performance. Here we show that mixing of the silicone oil into an LM-air foam yields emulsions with inverted phases. We investigate the stability of these oil-in-LM emulsions through a range of processing times and oil viscosities, and characterize the impact of these parameters on the materials' structure and thermal property relationships. We demonstrate that the emulsion with 40 vol% of 10 cSt silicone oil provides a unique thermal management material with a 10 W m-1 K-1 thermal conductivity and an exterior lubricant thin film that completely prevents corrosion of contacting aluminum.

Management of traumatic laryngotracheal separation: Case series and review.

Laryngotracheal separation injuries are a rare but serious condition, as survival from such injuries relies on proper airway management. As a result, recommendations for management have been based on small case reports and expert opinion. We reviewed our last 10 years of experience with managing laryngotracheal separation injuries and identified 6 cases for chart review. Awake tracheostomy or videolaryngobronchoscopy was used in each case to initially obtain the airway. Surgical repair was then performed immediately using nonabsorbable monofilament suture or a miniplate, and a low fenestrated tracheostomy was placed. All of our patients who followed up were decannulated, eating regular diets, and had satisfactory voice quality at 3 months postoperatively. Review of the literature revealed that, while management strategies have changed over time, treatment still varies widely depending on surgeon preference and the details of each injury. Outcomes from our series suggest that our described techniques and management strategies can be used with good outcomes. We believe that this is due to securing a safe airway, early surgical intervention with no unnecessary tissue dissection, effective reconstruction of the airway, and the fenestrated tracheostomy technique.

High Incidence and Early Onset of Urinary Tract Cancers in Patients with BK Polyomavirus Associated Nephropathy.

Over-immunosuppressed kidney transplant recipients are susceptible to malignancies and BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN). This study aimed to verify the association between BKPyV infection and urinary tract cancers (UTC). A total of 244 kidney transplant recipients were enrolled at Chang Gung Memorial Hospital from June 2000 to February 2020. Biopsy-proven BKPyVAN patients (n = 17) had worse kidney function (eGFR: 26 ± 13.7 vs. 47.8 ± 31.0 mL/min/1.73 m2). The 5-year allograft survival rates for patients with and without BKPyVAN were 67% and 93%, respectively (p = 0.0002), while the 10-year patient survival was not different between the two groups. BKPyVAN patients had a significantly higher incidence of UTC compared to the non-BKPyVAN group (29.4% vs. 6.6%). Kaplan-Meier analysis showed that the UTC-free survival rate was significantly lower in BKPyVAN patients, and the onset of UTC was significantly shorter in BKPyVAN patients (53.4 vs. 108.9 months). The multivariate logistic regression analysis demonstrated that age (RR = 1.062) and BKVAN (RR = 6.459) were the most significant risk factors for the development of UTC. Our study demonstrates that BKPyVAN patients have greater allograft losses, higher incidence, a lower cancer-free survival rate, and an earlier onset with a higher relative risk of developing UTC compared to non-BKPyVAN patients.