Incidence and survival of secondary malignancies after external beam radiotherapy for prostate cancer in the SEER database.

INTRODUCTION: We investigated the incidence of secondary bladder (BCa) and rectal cancers (RCa) after external beam radiotherapy (EBRT) for prostate cancer (PCa) compared to radical prostatectomy (RP) alone, and compared cancer-specific survival (CSS) of these secondary neoplasms to their primary counterparts. METHODS: This retrospective cohort study included men in the SEER cancer registry with a diagnosis of non-metastatic, clinically node-negative PCa treated with either RP or EBRT from 1995-2011 and allowed a minimum five-year lag period for the development of secondary BCa or RCa. Patients were divided into two eras, 1995-2002 and 2003-2011, to examine differences in incidence of secondary malignancies over time. Univariable and multivariable competing risk analyses with Fine-Gray subdistribution hazard and cause-specific hazard models were used to examine the risk of developing a secondary BCa or RCa. Competing risks analyses were used to compare CSS of primary vs. secondary BCa and RCa. RESULTS: A total of 198 184 men underwent RP and 190 536 underwent EBRT for PCa. The cumulative incidence of secondary BCa at 10 years was 1.71% for RP, and 3.7% for EBRT (p<0.001), while that of RCa was 0.52% for RP and 0.99% for EBRT (p<0.001). EBRT was associated with almost twice the risk of developing a secondary BCa and RCa compared to RP. The hazard of secondary BCa following EBRT delivered during 2003-2011 was 20% less than from 1995-2002 (p<0.09, Fine-Gray model), while that of secondary RCa was 31% less (p<0.001) (hazard ratio 0.78, p<0.001) for Fine-Gray and cause-specific hazard models. In the Fine-Gray model, the risk of death from BCa was 27% lower for secondary BCa after RP compared to primary BCa, while the risk of death was 9% lower for secondary BCa after EBRT compared to primary BCa. There was no difference in RCa-specific survival between primary or secondary RCa after RP or EBRT. CONCLUSIONS: The risk of BCa and RCa is almost twice as high for men undergoing EBRT for localized PCa vs. RP, but that risk is declining, likely reflecting advances in radiation delivery. The development of secondary RCa or BCa does not confer elevated risk of death compared to their primary counterparts.

Emerging Insights in Small-Cell Carcinoma of the Genitourinary Tract: From Diagnosis to Novel Therapeutic Horizons.

Small-cell carcinomas (SCCs) of the genitourinary (GU) tract are rare malignancies with high metastatic potential. The most common primary sites are the bladder and prostate, but case reports of primary SCC of the kidney, ureter, and urethra also exist. The majority of patients present with gross hematuria, irritative or obstructive urinary symptoms, and symptoms of locoregionally advanced or metastatic disease at initial presentation. SCC of the bladder presents with nodal or metastatic involvement in the majority of cases and requires the use of platinum-based chemotherapy in combination with surgery and/or radiation. SCC of the prostate is most commonly seen in the metastatic castrate-resistant setting, and aggressive variant disease presents with a greater propensity for visceral metastases, osteolytic lesions, and relatively low serum prostate-specific antigen for volume of disease burden. Multiple retrospective and prospective randomized studies support the use of a multimodal approach combining platinum-based systemic therapy regimens with radiation and/or surgery for localized disease. This evidence-based strategy is reflected in multiple consensus guidelines. Emerging data suggest that small-cell bladder and prostate cancers transdifferentiate from a common progenitor of conventional urothelial bladder carcinoma and prostatic acinar adenocarcinoma, respectively. Areas of active basic research include efforts to identify the key genetic and epigenetic drivers involved in the emergence of small cell cancers to exploit them for novel therapies. Here, we review these efforts, discuss diagnosis and currently supported management strategies, and summarize ongoing clinical trials evaluating novel therapies to treat this rare, aggressive GU cancer.

An Exploratory Pilot Study of Neuropsychological Performance in Two Huntington Disease Centers of Excellence Clinics.

OBJECTIVES: To describe the characteristics of patients receiving a clinical referral for neuropsychological evaluation in two Huntington's Disease Society of America Centers of Excellence (HDSA COE). In this exploratory pilot study, we used an empirically supported clinical neuropsychological battery to assess differences in cognitive performance between premanifest and manifest HD patient groups (compared with each other and normative expectations). METHOD: Clinical data from 76 adult genetically confirmed patients referred for neuropsychological evaluations was retrospectively collected from two HDSA COEs. ANOVA and Chi-square tests were used to compare variables between pre-manifest (n = 14) and manifest (n = 62) groups for demographic, cognitive, neuropsychiatric, and disease severity variables. RESULTS: Our clinics serviced a disproportionate number of motor manifest patients. Six measures were excluded from analyses due to infrequent administration. The full WAIS-IV Digit Span was disproportionately administered to the manifest group. The premanifest group showed stronger cognitive performance with effect sizes in the large range on subtests of the WAIS-IV Digit Span, HVLT-R, SDMT, and verbal fluency. CONCLUSIONS: This is the first study to assess an empirically supported neuropsychological research battery in a clinical setting with a relatively large sample size given the rarity of HD. The battery adequately captured areas of impairment across the disease spectrum. Application of the current battery with larger premanifest samples is warranted.

Characterization of the metabolomic profile of renal cell carcinoma by high resolution magic angle spinning proton magnetic resonance spectroscopy.

BACKGROUND: Renal cell carcinoma (RCC) is a metabolic disease, with subtypes exhibiting aberrations in different metabolic pathways. Metabolomics may offer greater sensitivity for revealing disease biology. We investigated the metabolomic profile of RCC using high-resolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy (1HMRS). METHODS: Surgical tissue samples were obtained from our frozen tissue bank, collected from radical or partial nephrectomy. Specimens were fresh-frozen, then stored at -80 °C until analysis. Tissue HRMAS-1HMRS was performed. A MatLab-based curve fitting program was used to process the spectra to produce relative intensities for 59 spectral regions of interest (ROIs). Comparisons of the metabolomic profiles of various RCC histologies and benign tumors, angiomyolipoma, and oncocytoma, were performed. False discovery rates (FDR) were used from the response screening to account for multiple testing; ROIs with FDR p < 0.05 were considered potential predictors of RCC. Wilcoxon rank sum test was used to compare median 1HMRS relative intensities for those metabolites that may differentiate between RCC and benign tumor. Logistic regression determined odds ratios for risk of malignancy based on the abundance of each metabolite. RESULTS: Thirty-eight RCC (16 clear cell, 11 papillary, 11 chromophobe), 10 oncocytomas, 7 angiomyolipomas, and 13 adjacent normal tissue specimens (matched pairs) were analyzed. Candidate metabolites for predictors of malignancy based on FDR p-values include histidine, phenylalanine, phosphocholine, serine, phosphocreatine, creatine, glycerophosphocholine, valine, glycine, myo-inositol, scyllo-inositol, taurine, glutamine, spermine, acetoacetate, and lactate. Higher levels of spermine, histidine, and phenylalanine at 3.15 to 3.13 parts per million (ppm) were associated with decreased risk of RCC (OR 4 × 10-5, 95% CI 7.42 × 10-8, 0.02), while 2.84 to 2.82 ppm increased the risk of malignant pathology (OR 7158.67, 95% CI 6.3, 8.3 × 106). The specific metabolites characterizing this region remain to be identified. Tumor stage did not affect metabolomic profile of malignant tumors, suggesting that metabolites are dependent on histologic subtype. CONCLUSIONS: HRMAS-1HMRS identified metabolites that may predict RCC. We demonstrated that those in the 3.14 to 3.13 ppm ROI were present in lower levels in RCC, while higher levels of metabolites in the 2.84 to 2.82 ppm ROI were associated with substantially increased risk of RCC. Further research in a larger population is required to validate these findings.

Botryoid-type of embryonal rhabdomyosarcoma of the proximal and mid ureter in an adult woman.

We report a unique case of botryoid-type embryonal RMS of the proximal and mid ureter in a pregnant 29-year-old woman. The ureteral polyp consisted of a malignant small blue round cell tumor with a myxoid background and contained evidence of foci of immature cartilage and aggregates of epithelial cells reminiscent of hair follicle. Immunohistochemical stains for myogenin and desmin confirmed skeletal muscle, or rhabdomyoblastic, differentiation. The compact epithelial cell fragments reminiscent of hair follicle differentiation were positive for p40. Treatment included 6 cycles of adjuvant chemotherapy (vincristine, actinomycin and cyclophosphamide (VAC). No recurrent or metastatic disease was identified post-surgery.

Myopericytoma of the ureter Incidental finding of a benign slowly growing tumor.

We present a unique case of a 6 cm, incidental, ureteral myopericytoma which was initially believed to be an ovarian tumor with mass effect, causing hydroureteronephrosis. A 75-year-old woman presented with a three-month history of postprandial cramps and heartburn. A right distal ureterectomy with en-bloc resection of the mass was performed. Histologically, a well-circumscribed, cellular proliferation of uniform, cytologically bland, spindle cells was identified that had a multilayered, concentric growth pattern around numerous blood vessels. Immunohistochemically, the spindle lesional cells stained strongly and diffusely with antibodies against smooth muscle actin and failed to stain for pancytokeratin and S100 protein.

X-ray therapy safety and awareness education for medical trainees and attending physicians.

INTRODUCTION: Medical imaging involving ionizing radiation is common in the clinical setting. Little is known about the level of radiation safety training for medical trainees and attending physicians. We sought to identify the level of radiation safety knowledge and training at the undergraduate, postgraduate, and attending physician level. METHODS: A 29-question survey was sent by email to two sites in Canada. We pooled the results of medical students, residents, and attending physicians. The primary outcome was to describe the amount of radiation safety training among these groups. The secondary outcomes were to describe the frequency of radiation exposure, level of radiation knowledge, and preferred training method for radiation safety. RESULTS: Of 115 surveys that were properly completed, 31 (26.9%) medical students, 17 (14.7%) residents, and 67 (58.3%) attending physicians responded. A greater number of medical students (41.9%) reported they had zero hours of training time for radiation safety compared to attending physicians (14.9%) (p<0.05). A higher number of attending physicians (47.8%) and residents (64.7%) participated in patient care involving fluoroscopy daily or at least several times per week compared to medical students (3.2%) (p<0.001). Attending physicians had the greatest number of correct responses to radiation safety questions. Online courses and workshops were the preferred training methods. CONCLUSIONS: Radiation safety training is an important component of medical education for medical trainees and attending physicians. Current radiation safety training requirements and procedures at various levels of medical training in Canada should be addressed. Implementing radiation safety education may improve adherence to the radiation safety principles.

Association of the USPSTF Grade D Recommendation Against Prostate-Specific Antigen Screening With Prostate Cancer-Specific Mortality.

Importance: The 2012 US Preventive Services Task Force (USPSTF) Grade D recommendation against prostate-specific antigen (PSA) screening for all men has been controversial, with data documenting a shift to a higher stage of disease at diagnosis. The association between the Grade D recommendation and prostate cancer-specific mortality (PCSM) among contemporary cohorts, however, is unclear. Objective: To evaluate PCSM rates between 1999 and 2019, comparing trends in rates before and after the change in the 2012 USPSTF screening guideline to assess its association with PCSM. Exposure: The 2012 USPSTF Grade D recommendation against PSA screening for all men. Design, Setting, and Participants: This cross-sectional study used Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research maintained by the National Center for Health Statistics to collect data on cause of death for all individuals who died of prostate cancer in the US from 1999 to 2019. Analysis was performed from January to August 2021. Main Outcomes and Measures: Trends in PCSM rates were calculated from 1999 to 2012 and from 2014 to 2019, with a washout year of 2013, using linear regression, with year and binary indicator of pre-2013 and post-2013 status as interaction terms. Trends were further analyzed by age, race and ethnicity, urbanization category, and US Census region. Other measures included diagnosis of localized or metastatic prostate cancer and overall cancer mortality. Results: A total of 618 095 patients died of prostate cancer in the US from 1999 to 2019. Age-adjusted PCSM decreased linearly at a rate of -0.273 per 100 000 population per year from 1999 to 2012 and stalled at a rate of -0.009 per 100 000 per year from 2014 to 2019 (P < .001). This finding was significant among men aged 60 years or older, especially among men aged 60 to 69 years, men aged 80 years or older, and among Black men. Men aged 60 to 64 years had a decreasing, age-adjusted PCSM rate of -0.0088 per 100 000 population per year prior to 2013 followed by an increasing rate of 0.0014 per 100 000 per year. Men aged 65 to 69 years had a decreasing, age-adjusted PCSM rate of -0.024 per 100 000 population per year prior to 2013 followed by an increasing rate of 0.0011 per 100 000 population per year. Men aged 80 years or older had the largest absolute difference between rates before and after 2013 compared with all other age groups, with a difference of 0.06 for men aged 80 to 84 years and 0.07 for men 85 aged years or older. Black men had a decreasing, age-adjusted PCSM rate of -0.700 per 100 000 population per year prior to 2013 followed by a flattened rate of -0.091 per 100 000 population per year. Changes were observed across races and ethnicities, urbanization categories, and US Census regions and were accompanied by increased diagnoses of metastatic disease, which are inconsistent with mortality trends across all malignant neoplasms. Conclusions and Relevance: This cross-sectional study using comprehensive PCSM data through 2019 demonstrated decreasing PCSM rates that flattened or increased after the 2012 USPSTF Grade D recommendation, suggesting that decreased PSA screening may be a factor associated with this change. This change was seen across ages, races and ethnicities, urbanization categories, and US Census regions. The updated 2018 USPSTF guideline supporting shared decision-making may reverse these trends in the coming years.

A unique case of chromophobe renal cell carcinoma seeding after biopsy.

We report a unique case for a 1.5 cm Chromophobe Renal Cell Carcinoma (ChRCC) tumor recurrence on the posterior abdominal wall along the renal tumor biopsy tract. This case presented on follow up at 4.5 years after radical nephrectomy T1bN0M0. Pathology was confirmed to be a chRCC with later excision of the mass. We believe the recurrence in this case is due to tumor seeding after multiple Renal Tumor biopsies (RTB) performed before surgery, as the tumor was located along the RTB tract.

A Randomized Controlled Trial of a Modified Cystoscopy Technique using the Peak-End Rule in order to Improve Pain and Anxiety.

OBJECTIVE: To determine if a modified cystoscopy technique utilizing the peak-end rule cognitive bias decreases pain and anxiety during flexible cystoscopy in patients who undergo cystoscopy. METHODS: A total of 85 participants undergoing their first diagnostic cystoscopy were enrolled in a blinded single-center, prospective, randomized controlled trial. Patients with lower urinary tract abnormalities, prior radiation and chronic pelvic pain were excluded. Participants were randomized to a standard cystoscopy (arm A) or a modified cystoscopy (arm B) where a two-minute period at the end of the procedure was completed during which the cystoscope was left in the bladder without being manipulated. Following the cystoscopy, participants completed a standard pain and anxiety questionnaire. Differences in mean pain and anxiety score between arms were evaluated using a Mann-Whitney test with a two-sided alpha of 0.05. RESULTS: Eighty-five patients were randomized and underwent flexible cystoscopy. Three participants were ineligible, one required secondary procedures, and two did not complete the questionnaires. Among the 82 eligible patients, 45 were randomized to standard cystoscopy (arm A) and 37 to the modified cystoscopy (arm B) with mean pain scores of 23.20 and 11.97, respectively (P = .039). Mean anxiety scores were 2.09 and 0.88 for arm A and B, respectively (P = .013). CONCLUSION: This study demonstrated a clinically meaningful decrease in pain and anxiety for patients undergoing flexible cystoscopy when employing the modified cystoscopy technique versus the standard practice. This free and straightforward method to improve patient comfort and decrease stress during first time flexible cystoscopy should be considered by clinicians.

Patient factors predict complications after partial nephrectomy: validation and calibration of the Preoperative Risk Evaluation for Partial Nephrectomy (PREP) score.

OBJECTIVES: To develop and validate the Preoperative Risk Evaluation for Partial Nephrectomy (PREP) score to predict the probability of major postoperative complications after partial nephrectomy (PN) based on patient comorbidities. PATIENTS AND METHODS: The Premier Healthcare Database was used to identify patients who had undergone elective PN. Through review of International Classification of Diseases ninth revision codes, we identified patient comorbidities and major surgical complications (Clavien-Dindo Grade III-V). Multivariable logistic regression was used to identify predictors of major complications. We used half of the set as the training cohort to develop our risk score and the other half as a validation cohort. RESULTS: From 2003 to 2015, 25 451 PNs were performed. The overall rate of major complications was 4.9%. The final risk score consisted of 10 predictors: age, sex, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, diabetes, hypertension, obesity, and smoking. In the training cohort, the area under the receiver operating characteristic curve (AUC) was 0.75 (95% confidence interval [CI] 0.73-0.78), while the AUC for the validation cohort was 0.73 (95% CI 0.70-0.75). The predicted probabilities of major complication in the low- (≤10 points), intermediate- (11-20 points), high- (21-30 points), and very high-risk (>30 points) categories were 3% (95% CI 2.6-3.2), 8% (95% CI 7.2-9.2), 24% (95% CI 20.5-27.8), and 41% (95% CI 34.5-47.8), respectively. CONCLUSIONS: We developed and validated the PREP score to predict the risk of complications after PN based on patient characteristics. Calculation of the PREP score can help providers select treatment options for patients with a cT1a renal mass and enhance the informed consent process for patients planning to undergo PN.

The cost of obesity in radical cystectomy.

INTRODUCTION: The prevalence of obesity is on the rise in the Unites States, and obesity has been associated with increased complications and costs in a variety of complex surgeries. However, the contribution of obesity to the overall costs of radical cystectomy has not been studied in detail using contemporary data. Our objective is to assess the variation in healthcare costs due to obesity on the index hospitalization for radical cystectomy in the United States between 2003 and 2015. MATERIALS AND METHODS: This was a retrospective cohort study, using the Premier Healthcare Database, of 1,242 patients who underwent radical cystectomy and were either overweight (25  ≤  body mass index [BMI] < 30), obese (30  ≤  BMI < 40), or morbidly obese (BMI ≥ 40). The primary outcome costs of the index hospitalization for each BMI category. Multivariable median regression was used to identify drivers of increased costs. RESULTS: The cost of the index hospitalization for cystectomy was $24,596 (95% confidence interval [CI], $22,599-$26,592) for overweight patients. The costs for obese and morbidly obese patients were $2,158 (95% CI, -$80 to $4,395, P = 0.059) and $5,308 (95% CI, $2,652-$7,964, P < 0.001) higher compared to overweight patients, respectively. After adjustment for operative time or length of stay in the multivariable models, there were no longer any differences in cost. Operative time was prolonged as BMI increased (median operative time for overweight, obese, and morbidly obese: 346, 391, and 420 minutes, respectively P = 0.0001). Median length of stay was 1 day shorter for overweight vs. morbidly obese patients (P = 0.0030), with each additional day costing $1,738 (95% CI, $1,654 to $1,821, P < 0.0001) on multivariable analysis. CONCLUSIONS: The cost of radical cystectomy is greater for obese and morbidly obese patients compared to overweight patients. The increased financial cost is driven by increased operative times and longer length of stay.

Fractional Limb Volume in Spina Bifida Fetuses as an Assessment Tool for Postnatal Ambulation.

BACKGROUND: Prenatal fractional limb volume (FLV) can be used to assess muscle atrophy in fetuses with myelomeningocele. OBJECTIVE: We hypothesize that FLV in fetal myelomeningocele (fMMC) repair is different from postnatal repair (PNR). Assessing intrauterine muscle development can predict ambulation. METHODS: A prospective observational study was performed from July 2012 to April 2016. Demographics, clinical outcomes, and FLV of the fetal thigh were assessed by ultrasound. Ambulation videos were collected from patients over 30 months of age. FLV was compared between the fMMC and PNR groups and between ambulators and non-ambulators. Two-sample t test, ANOVA, Spearman's rho correlation, and Bland-Altman plots were used for analysis. A p value <0.05 was used for statistical significance. RESULTS: Fifty-nine patients were included, 24 had fMMC and 35 had PNR. Videos were obtained in 47 cases (73%). There was no difference in baseline demographics between the groups. There was no significant change in the fMMC group between the FLV at initial presentation and the repeat at 34 weeks gestation (54.5 ± 28.2 and 62.2% ± 16.4; p = 0.6). In contrast, the FLV in the PNR decreased between the initial evaluation and the repeat at 34 weeks (54.1 ± 27.7 to 35.8 ± 34.1%; p = 0.04). FLV at 34 weeks gestation was higher in the fMMC group as compared to the PNR group (62.2 ± 16.4 vs. 35.8 ± 34.1%; p = 0.02). There was no difference in FLV between ambulators and non-ambulators either at initial evaluation (p = 0.8) or at 34 weeks gestation (p = 0.6). CONCLUSION: Lower FLV in the PNR group compared to fMMC may suggest in utero muscle atrophy. No correlation was seen between FLV and subsequent ambulation; however, future larger studies may be needed.

Differences in survival and impact of adjuvant chemotherapy in patients with variant histology of tumors of the renal pelvis.

BACKGROUND: The impact of variant histologies on overall survival (OS), as well as their influence on the response to neoadjuvant and adjuvant chemotherapy (AC) is well studied in patients diagnosed with bladder cancer. However, little is known about tumors with variant histologies of the upper urinary tract. The objective of this study was to assess the survival of the predominant variant histologies of tumors of the renal pelvis (RPT) after surgical intervention, and to examine the influence of AC on the OS of the different variant histologies. METHODS: We identified 21,318 patients with RPT undergoing surgical intervention using the National Cancer Database for the period 2004-2015. We employed multivariable Cox proportional hazards regression models and Kaplan-Meier curves to evaluate the OS according to variant histology. Separate multivariable Cox regression models were used to assess the specific effect of AC on OS of the histological subgroups. RESULTS: The majority of patients were diagnosed with pure urothelial carcinoma (PUC) (96.1%). Overall, 826 patients were diagnosed with variant histologies (adenocarcinoma N = 298, squamous cell carcinoma N = 291, sarcomatoid N = 137, others N = 100). Compared to PUC, adenocarcinomas showed longer OS (HR 0.76, 95% confidence interval (CI) 0.62-0.94, p = 0.01), while sarcomatoid tumors had shorter OS (HR 1.59, 95% CI 1.12-2.26, p = 0.011). A subgroup analysis of patients undergoing AC showed a survival benefit in patients with PUC (HR 0.81, 95% CI 0.73-0.9, p < 0.001). CONCLUSION: We found that variant histologies of upper urinary tract carcinomas exhibit different survival rates and that AC was only associated with an OS benefit in patients with PUC.

Early Administration of Magnesium Sulfate during Open Fetal Myelomeningocele Repair Reduces the Dose of Inhalational Anesthesia.

INTRODUCTION: Optimal uterine relaxation is achieved through higher minimum alveolar concentration (MAC) of inhalational anesthetics, increasing risks to mother and fetus. Our objective was to determine if earlier administration of magnesium sulfate would reduce the requirement of inhalational anesthetics in fetal myelomeningocele repair. MATERIALS AND METHODS: Prospective observational study of fetal myelomeningocele repair was performed from September 2011 to August 2017. Groups compared were: (1) magnesium sulfate at uterine closure; (2) magnesium sulfate at maternal skin incision. Maternal demographics, anesthetic agents, intraoperative complications, and pregnancy outcomes were reviewed. A Student t test was used for analysis. RESULTS: There were 30 cases in group 1 and 21 cases in group 2. There was no difference in gestational age at intervention (24.92 ± 0.62 vs. 25.22 ± 0.47 weeks, p = 0.07) or at delivery (34.83 ± 2.77 vs. 33.98 ± 3.83 weeks, p = 0.38) between groups 1 and 2, respectively. The maximum MAC of sevoflurane was significantly lower in group 2 (1.84 ± 0.25 vs. 1.05 ± 0.28, p < 0.0001). There was no difference in the average dose of phenylephrine used. DISCUSSION: Magnesium sulfate infusion initiated earlier in open fetal surgery reduces the total anesthetic exposure to the fetus.

Evaluating the cost of surveillance for non-muscle-invasive bladder cancer: an analysis based on risk categories.

INTRODUCTION: Non-muscle-invasive bladder cancer (NMIBC) is a biologically heterogeneous disease and is one of the most expensive malignancies to treat on a per patient basis. In part, this high cost is attributed to the need for long-term surveillance. We sought to perform an economic analysis of surveillance strategies to elucidate cumulative costs for the management of NMIBC. METHODS: A Markov model was constructed to determine the average 5-year costs for the surveillance of patients with NMIBC. Patients were stratified into low, intermediate, and high-risk groups based on the EORTC risk calculator to determine recurrence and progression rates according to each category. The index patient was a compliant 65-year-old male. A total of four health states were utilized in the Markov model: no evidence of disease, recurrence, progression and cystectomy, and death. RESULTS: Cumulative costs of care over a 5-year period were $52,125 for low-risk, $146,250 for intermediate-risk, and $366,143 for high-risk NMIBC. The primary driver of cost was progression to muscle-invasive disease requiring definitive therapy, contributing to 81% and 92% of overall cost for intermediate- and high-risk disease. Although low-risk tumors have a high likelihood of 5-year recurrence, the overall cost contribution of recurrence was 8%, whereas disease progression accounted for 71%. CONCLUSION: Although protracted surveillance cystoscopy contributes to the expenditures associated with NMIBC, progression increases the overall cost of care across all three patient risk groups and most notably for intermediate- and high-risk disease patients.

A case control analysis investigating risk factors and outcomes for nephrocalcinosis and renal calculi in neonates.

INTRODUCTION: Studies on outcomes and risk factors for neonatal nephrocalcinosis (NC) and renal calculi (RC) are limited, and often do not include controls for comparison. We conducted a case-control analysis to identify risk factors associated with NC and/or RC in neonates and studied the natural course of these anomalies. STUDY DESIGN: Infants diagnosed with NC/RC on ultrasound within the first year of life and corresponding gestational age- and gender-matched controls were identified from the neonatal intensive care unit database at our institution over a 10-year period. Risk factors assessed included: low birth weight, small for gestational age, nephrotoxic drugs, respiratory support therapy, use of total parental nutrition (TPN), surgeries, history of UTIs, creatinine at presentation, and history of maternal hypertension. Unadjusted odds ratios were estimated. Chi square analysis was performed for binary variables and the Mann-Whitney U test for continuous variables. Outcomes examined include time to resolution of NC/RC, renal function, and hypertension. RESULTS: We identified 22 cases of NC/RC with corresponding matched controls. Median follow-up was 28 months (IQR 0-122 months). History of urinary tract infections (UTI) was the only variable significantly associated with the presence of NC/RC (OR 5.62, 95% CI 1.12-31.1, p < 0.013) (Table). All other known risk factors were comparable in both groups. There was no difference in the incidence of hypertension (OR 2.94, 95% CI 0.40-33.82, p = 0.216) at diagnosis or last follow-up between the groups. Resolution of NC/RC was observed in 72.7%, during a median follow-up of 12.1 months. Mean urinary calcium/creatinine ratio for the NC/RC group was 2.3 ± 1.5 at diagnosis and 0.96 ± 0.8 at last follow-up. DISCUSSION: Most NC/RC in infants resolve without surgical intervention but some infants require medical therapy and follow-up. Risk factors for NC/RC in neonates continue to be poorly defined because of the quality of studies available. Our study provides further adjustment for confounders but has a small sample size and is restricted to neonates from an intensive care unit. CONCLUSION: Most cases of NC/RC resolve spontaneously without surgical intervention. The mean time to resolution is 12.1 months, without untoward consequences in terms of hypertension. A history of UTIs is the only identified risk factor identified in this study which is associated with a significant increased risk of neonatal nephrocalcinosis and/or renal calculi. Larger prospective studies are warranted to confirm these findings.