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Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard for muscle-invasive bladder cancer (MIBC), however, NAC confers only a small survival benefit and new strategies are needed to increase its efficacy. Pre-clinical data suggest that in response to DNA damage the tumor microenvironment (TME) adopts a paracrine secretory phenotype dependent on mTOR signaling which may provide an escape mechanism for tumor resistance, thus offering an opportunity to increase NAC effectiveness with mTOR blockade.

Altered adipose tissue (AT) metabolism in cancer‐associated weight loss via inflammation, lipolysis, and white adipose tissue (WAT) browning is primarily implicated from rodent models; their contribution to AT wasting in cancer patients is unclear. Energy expenditure (EE), plasma, and abdominal subcutaneous WAT were obtained from men (aged 65 ± 8 years) with cancer, with (CWL, n= 27) or without (CWS, n= 47) weight loss, and weight‐stable non‐cancer patients (CON, n= 26). Clinical images were assessed for adipose and muscle area while plasma and WAT were assessed for inflammatory, lipolytic, and browning markers. CWL displayed smaller subcutaneous AT (SAT; P= 0.05) and visceral AT (VAT; P= 0.034) than CWS, and displayed higher circulating interleukin (IL)‐6 (P= 0.01) and WAT transcript levels of IL‐6(P= 0.029), IL‐1β(P= 0.042), adipose triglyceride lipase (P= 0.026), and browning markers (Dio2, P= 0.03; PGC‐1a, P= 0.016) than CWS and CON. There was no difference across groups in absolute REE (P= 0.061), %predicted REE (P= 0.18), circulating free fatty acids (FFA, P= 0.13) or parathyroid hormone‐related peptide (PTHrP; P= 0.88), or WAT protein expression of inflammation (IL‐6, P= 0.51; IL‐1β, P= 0.29; monocyte chemoattractant protein‐1, P= 0.23) or WAT protein or gene expression of browning (uncoupling protein‐1, UCP‐1; P= 0.13, UCP‐1, P= 0.14). In patients with cancer, FFA was moderately correlated with WAT hormone‐sensitive lipase transcript (r= 0.38, P= 0.018, n= 39); circulating cytokines were not correlated with expression of WAT inflammatory markers and circulating PTHrP was not correlated with expression of WAT browning markers. In multivariate regression using cancer patients only, body mass index (BMI) directly predicted SAT (N= 25, R2= 0.72, P< 0.001), VAT (N= 28, R2= 0.64, P< 0.001), and absolute REE (N= 22, R2= 0.43, P= 0.001), while BMI and WAT UCP‐1 protein were indirectly associated with %predicted REE (N= 22, R2= 0.45, P= 0.02), and FFA was indirectly associated with RQ (N= 22, R2= 0.52, P< 0.001). Cancer‐related weight loss was associated with elevated circulating IL‐6 and elevations in some WAT inflammatory, lipolytic and browning marker transcripts. BMI, not weight loss, was associated with increased energy expenditure. The contribution of inflammation and lipolysis, and lack thereof for WAT browning, will need to be clarified in other tumour types to increase generalizability. Future studies should consider variability in fat mass when exploring the relationship between cancer and adipose metabolism and should observe the trajectory of lipolysis and energy expenditure over time to establish the clinical significance of these associations and to inform more mechanistic interpretation of causation.

Background: For men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification. Methods: Urine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: Seven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0–1.7, p= 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies. Conclusions: PCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies.

We evaluated the roleof race, socioeconomic status, andregionalization in the disparities in testicular cancer care using retrospectiveanalysis of a large hospital-based cohort. We found that underinsured and nonwhite patients experiencegreater disparity. This could be mediatedby regionalization of care.

Retroperitoneal lymph node dissection after chemotherapy has a proved role in the staging and treatment of metastatic testicular cancer. Complete removal of all postchemotherapy residual masses in nonseminomatous germ cell tumor should be performed. Complete removal of positron emission tomography–avid masses greater than 3 cm in pure seminoma should be performed. Outcomes depend on patient selection and extent of surgery.

Background A 35-year -old man presented to a local emergency room with acute left-flank pain and a medical history of nephrolithiasis. There were no aggravating or relieving factors for the left-flank pain and no other presenting symptoms, and the physical examination was unremarkable.Investigations Complete blood count, urinalysis, serum tumor markers, scrotal ultrasonography, CT scan of the abdomen (with and without contrast), MRI of the abdomen.Diagnosis Unicentric Castleman's disease (hyaline-vascular type).Management Surgical exploration and excision. Pathologic and immunohistochemical work-up confirmed the diagnosis. CT scan after 7 months was normal with no evidence of recurrence.

The expression of thousands of genes can be monitored simultaneously using cDNA microarray technology. This technology is being used to understand the complexity of human disease. One significant technical concern regards potential alterations in gene expression because of the effect of tissue ischemia. This study evaluates the increase in the differential gene expression because of tissue processing time. To evaluate differential gene expression because of ischemia time, prostate samples were divided into five time points (0, 0.5, 1, 3, and 5 hours). Each time point consisted of a homogeneous mixture of 12 to 15 prostate tissue cubes (5 mm3). These tissues were maintained at room temperature until at the assigned time point the tissue was placed in OCT, flash frozen in liquid nitrogen, and stored at −80°C until RNA extraction. RNA from each time point was hybridized against an aliquot of 0 time point RNA from the same prostate. Four prostate glands were used in parallel studies. M-A plots were graphed to compare variability between time point sample hybridizations. Statistical Analysis of Microarray software was used to identify genes overexpressed at the 1-hour time point versusthe 0-hour time with statistically significance. Microarray analysis revealed only a small percentage of genes (<0.6%) from more than 9000 to demonstrate overexpression at the 1-hour time point. Among the 41 statistically significant named overexpressed genes at the 1-hour time point were early growth response 1 (EGR1), jun B proto-oncogene (jun B), jun D proto-oncogene (jun D), and activating transcription factor 3 (ATF3). Genes previously associated with prostate cancer did not have significantly altered expression with ischemia time. Increased EGR1 protein expression was confirmed by Western blot analysis. Microarray technology has opened the possibility of evaluating the expression of a multitude of genes simultaneously, however, the interpretation of this complex data needs to be assessed circumspectly using refined statistical methods. Because RNA expression represents the tissue response to insults such as ischemia, and is also sensitive to degradation, investigators need be mindful of confounding artifacts secondary to tissue processing. All attempts should be made to process tissue rapidly to ensure that the microarray gene profile accurately represents the state of the cells and confirmatory studies should be performed using alternative methods (eg, Northern blot analysis, Western blot, immunohistochemistry).

The gene 59 protein (gp59) of bacteriophage T4 stimulates the activities of gene 41 protein (gp41), the T4 replicative DNA helicase, by promoting the assembly of gp41 onto single-stranded (ss)-DNA molecules that are covered with cooperatively bound gene 32 protein (gp32). This helicase-ssDNA assembly process, which is important for the reconstitution of the primosome component of the T4 DNA replication fork, appears to require both gp59-gp41 and gp59-gp32 protein-protein interactions. In this study we characterize the physical and functional interactions of gp59 with gp32, the T4 ssDNA-binding protein. Experimental results presented herein indicate: 1) that gp59 binds specifically to both free and ssDNA-bound gp32 molecules; and 2) that in both cases binding involves contacts between gp59 and the acidic C-terminal domain of gp32 (the so-called “A-domain”). We further show that single-stranded DNA molecules coated with (gp32-A), a truncated form of gp32 lacking the A-domain, are refractory to gp59-dependent helicase assembly. The data indicate that specific contacts between gp59 molecules and the A-domains of gp32 molecules are essential for gp59-dependent assembly of gp41 onto gp32-ssDNA complexes. Our results are consistent with a model in which gp59 binds to gp32 molecules within the gp32-ssDNA complex and therein forms a target site for helicase-ssDNA assembly.

IMPORTANCE: Active surveillance is increasingly recognized as the preferred standard of care for men with low-risk prostate cancer. However, active surveillance requires repeated assessments, including prostate-specific antigen tests and biopsies that may increase anxiety, risk of complications, and cost. OBJECTIVE: To identify and validate clinical parameters that can identify men who can safely defer follow-up prostate cancer assessments. DESIGN, SETTING, AND PARTICIPANTS: The Canary Prostate Active Surveillance Study (PASS) is a multicenter, prospective active surveillance cohort study initiated in July 2008, with ongoing accrual and a median follow-up period of 4.1 years.Men with prostate cancer managed with active surveillance from 9 North American academic medical centers were enrolled. Blood tests and biopsies were conducted on a defined schedule for least 5 years after enrollment. Model validation was performed among men at the University of California, San Francisco (UCSF) who did not enroll in PASS. Men with Gleason grade group 1 prostate cancer diagnosed since 2003 and enrolled in PASS before 2017 with at least 1 confirmatory biopsy after diagnosis were included. A total of 850 men met these criteria and had adequate follow-up. For the UCSF validation study, 533 active surveillance patients meeting the same criteria were identified. Exclusion criteria were treatment within 6 months of diagnosis, diagnosis before 2003, Gleason grade score of at least 2 at diagnosis or first surveillance biopsy, no surveillance biopsy, or missing data. EXPOSURES: Active surveillance for prostate cancer. MAIN OUTCOMES AND MEASURES: Time from confirmatory biopsy to reclassification, defined as Gleason grade group 2 or higher on subsequent biopsy. RESULTS: A total of 850 men (median [interquartile range] age, 64 [58-68] years; 774 [91%] White) were included in the PASS cohort. A total of 533 men (median [interquartile range] age, 61 [57-65] years; 422 [79%] White) were included in the UCSF cohort. Parameters predictive of reclassification on multivariable analysis included maximum percent positive cores (hazard ratio [HR], 1.30 [95% CI, 1.09-1.56]; P = .004), history of any negative biopsy after diagnosis (1 vs 0: HR, 0.52 [95% CI, 0.38-0.71]; P &lt; .001 and ≥2 vs 0: HR, 0.18 [95% CI, 0.08-0.4]; P &lt; .001), time since diagnosis (HR, 1.62 [95% CI, 1.28-2.05]; P &lt; .001), body mass index (HR, 1.08 [95% CI, 1.05-1.12]; P &lt; .001), prostate size (HR, 0.40 [95% CI, 0.25-0.62]; P &lt; .001), prostate-specific antigen at diagnosis (HR, 1.51 [95% CI, 1.15-1.98]; P = .003), and prostate-specific antigen kinetics (HR, 1.46 [95% CI, 1.23-1.73]; P &lt; .001). For prediction of nonreclassification at 4 years, the area under the receiver operating curve was 0.70 for the PASS cohort and 0.70 for the UCSF validation cohort. This model achieved a negative predictive value of 0.88 (95% CI, 0.83-0.94) for those in the bottom 25th percentile of risk and of 0.95 (95% CI, 0.89-1.00) for those in the bottom 10th percentile. CONCLUSIONS AND RELEVANCE: In this study, among men with low-risk prostate cancer, heterogeneity prevailed in risk of subsequent disease reclassification. These findings suggest that active surveillance intensity can be modulated based on an individual’s risk parameters and that many men may be safely monitored with a substantially less intensive surveillance regimen.

Cystic nephroma is a rare, presumed benign, renal tumor that occurs in both children and adults. When its presence is suspected preoperatively, nephron-sparing surgery can be applied. We describe treatment of a cystic nephroma that is the first reported, to our knowledge, using endoscopic techniques.

Desmoplastic melanomas are rare amelanotic melanomas that usually occur on skin with sun exposure. In this report, we present a 72-year-old man who presented with a desmoplastic melanoma of the penis. To our knowledge this represents the first reported case of primary desmoplastic melanoma of the penis. We discuss the pathologic differential and histologic evaluation.