Management of Renal Cell Carcinoma With Supradiaphragmatic Inferior Vena Cava Thrombus Diagnosed During Acute COVID-19 Infection.

Renal cell carcinoma (RCC) tends to undergo intravascular tumor growth along the renal vein, forming tumor thrombi that may extend into the inferior vena cava (IVC) or even the right atrium (Level IV). Managing such cases requires a multidisciplinary approach, especially in patients with acute coronavirus disease 2019 (COVID-19) infection, who face increased risks from surgical interventions. We present a case of RCC with Level IV thrombus and concurrent COVID-19 managed with systemic therapy. We also summarize current literature on treating RCC with IVC thrombus and COVID-19's impact on prognosis. The patient was a 70-year-old female with incidental detection of a 9-cm right heterogeneous renal mass with a supradiaphragmatic tumor thrombus during COVID-19 infection. Due to ongoing pulmonary symptoms, systemic therapy with a combination of ipilimumab and nivolumab was initiated. After an excellent initial response, the patient continued systemic therapy, maintaining a necrotic response in the renal mass and tumor thrombus. The patient continues to tolerate systemic therapy well. We report a rare case of RCC with Level IV tumor thrombus and synchronous acute COVID-19 infection. Our report depicts successful management utilizing systemic therapy with a combination of ipilimumab and nivolumab. The management of such cases necessitates a comprehensive, multidisciplinary approach, considering the risks associated with surgery in the context of recent COVID-19 infection. The case presentation and ensuing literature discussion of the dynamic landscape of RCC management highlights the need for more research to improve treatment plans and guide clinicians in handling such complex situations.

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

Does Rounding Order Bias Discharge Efficiency? Predictors of Discharge Timing on an Academic Urology Service.

ABSTRACT: No previous works have analyzed whether the order in which surgical teams see patients on morning rounds affects discharge efficiency at teaching hospitals. We obtained perioperative urologic surgery timing data at our academic institution from 2014 to 2019. We limited the analysis to routine postoperative day 1 discharges. Univariate and multivariate analyses were performed to determine whether various hospital and patient factors were associated with discharge timing. We analyzed 1,494 patients. Average discharge order time was 11:22 a.m. and hospital discharge 1:24 p.m. Univariate regression revealed earlier discharge order time for patients seen later in rounds by 4 minutes per sequential room cluster (p = .013) and by 12 minutes per cluster when excluding short-stay patients. Multivariate analysis revealed discharge order placement did not vary significantly by rounding order. However, time of hospital discharge did (p < .001), likely due to speed of discharge in the designated short-stay units. Attending physician was the most consistent predictor in variations of discharge timing, with statistical significance across all measured outcomes. Patients seen later in rounding progression received earlier discharge orders, but this relationship does not remain in multivariate modeling or translate to earlier discharge. These findings have helped guide quality improvement efforts focused on discharge efficiency.

Interruptions in bladder cancer care during the COVID-19 public health emergency.

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.

Technique and outcomes of robotic-assisted retroperitoneal radical nephrectomy.

Background: Robotic retroperitoneal partial nephrectomy (rRPN) has numerous advantages over transperitoneal surgery, including direct access to the renal hilum and posterior tumors, and avoidance of the peritoneal cavity in patients with a hostile abdomen. Although the use of the retroperitoneal approach has increased over the last decade, there is little literature on robotic retroperitoneal radical nephrectomy (rRRN), which has similar benefits over the transperitoneal approach. The aim of this study was to describe our technique for robotic retroperitoneal nephrectomy (rRN) and assess its feasibility and outcomes at a high-volume center. Methods: A retrospective review of patients who underwent some form of rRN [rRRN, robotic retroperitoneal simple nephrectomy (rRSN), or robotic retroperitoneal nephroureterectomy (rRNU)] at a single institution between 2013 and 2023. Patient characteristics, operative data, and postoperative complication rates were assessed. The technique for rRN was detailed. Results: A total of 13 renal units in 12 patients were included for analysis (7 rRRN, 5 rRSN, 1 rRNU). Median patient age was 64.0 years, and median body mass index (BMI) was 36.0 kg/m2. Indications for retroperitoneal surgery were prior abdominal surgery in all patients, including three with bowel diversions, super morbid central obesity in two patients, and a large ventral hernia in one patient. Median operative time was 213 minutes and median estimated blood loss (EBL) was 85 cc. Median postoperative length of stay (LOS) was 3 days, and only one patient experienced a Clavien-Dindo grade ≥3 complication within 90 days of surgery. Conclusions: The retroperitoneal approach for robotic-assisted nephrectomy is feasible and associated with similar outcomes as the transperitoneal approach. This approach may prove beneficial in select patients with significant prior abdominal surgery including those who are morbidly obese.

Impact of a switch to immediate release on the patient viewing of diagnostic test results in an online portal at an academic medical center.

Patient portals allow patients to access their personal health information. The 21st Century Cures Act in the United States sought to eliminate 'information blocking', requiring timely release upon request of electronic health information including diagnostic test results. Some health systems, including the one in the present study, chose a systematic switch to immediate release of all or nearly all diagnostic test results to patient portals as part of compliance with the Cures Act. Our primary objective was to study changes in the time to view test results by patients before and after implementation of Cures Act-related changes. This retrospective pre-post study included data from two 10-month time periods before and after implementation of Cures Act-related changes at an academic medical center. The study included all patients (adult and pediatric) with diagnostic testing (laboratory and imaging) performed in the outpatient, inpatient, or emergency department settings. Between February 9, 2020 and December 9, 2021, there was a total of 3 809 397 diagnostic tests from 204 605 unique patients (3 320 423 tests for adult patients; 488 974 for pediatric patients). Overall, 56.5% (115 627) of patients were female, 84.1% (172 048) white, and 96.5% (197 517) preferred English as primary language. The odds of viewing test results within 1 and 30 days after portal release increased monthly throughout both time periods before and after the Cures Act for all patients. The rate of increase was significantly higher after implementation only in the subgroup of tests belonging to adult patients with active MyChart accounts. Immediate release shifted a higher proportion of result/report release to weekends (3.2% pre-Cures vs 15.3% post-Cures), although patient viewing patterns by day of week and time of day were similar before and after immediate release changes. The switch to immediate release of diagnostic test results to the patient portal resulted in a higher fraction of results viewed within 1 day across outpatient, inpatient, and emergency department settings.

Interprofessional implementation of the Global Malnutrition Composite Score quality measure.

Malnutrition in hospitalized patients can impact health outcomes, quality of life, and health equity. Quality improvement initiatives and quality measurement can help improve the care of those hospitalized patients with malnutrition. The new Global Malnutrition Composite Score (GMCS) was recently adopted by the Centers for Medicare & Medicaid Services (CMS) as a health equity-focused measure. Beginning in 2024, the GMCS is available for reporting through the CMS Hospital Inpatient Quality Reporting Program. The GMCS provides an opportunity to elevate the importance of patient nutrition status and evidence-based interventions throughout the interdisciplinary hospital decision-making process. To promote this opportunity, the American Society for Parenteral and Enteral Nutrition (ASPEN) held an "Interprofessional implementation of the Global Malnutrition Composite Score" webinar as part of its 2022 Malnutrition Awareness Week programming. This article summarizes the underlying rationale and significance of the GMCS measure and showcases clinical observations about integrating quality improvement and measurement into the acute care setting, as presented during the webinar.

Pan-cancer Landscape of Programmed Death Ligand-1 and Programmed Death Ligand-2 Structural Variations.

PURPOSE: Programmed cell death protein-1 (PD-1) receptor and ligand interactions are the target of immunotherapies for more than 20 cancer types. Biomarkers that predict response to immunotherapy are microsatellite instability, tumor mutational burden, and programmed death ligand-1 (PD-L1) immunohistochemistry. Structural variations (SVs) in PD-L1 (CD274) and PD-L2 (PDCD1LG2) have been observed in cancer, but the comprehensive landscape is unknown. Here, we describe the genomic landscape of PD-L1 and PD-L2 SVs, their potential impact on the tumor microenvironment, and evidence that patients with these alterations can benefit from immunotherapy. METHODS: We analyzed sequencing data from cancer cases with PD-L1 and PD-L2 SVs across 22 publications and four data sets, including Foundation Medicine Inc, The Cancer Genome Atlas, International Cancer Genome Consortium, and the Oncology Research Information Exchange Network. We leveraged RNA sequencing to evaluate immune signatures. We curated literature reporting clinical outcomes of patients harboring PD-L1 or PD-L2 SVs. RESULTS: Using data sets encompassing 300,000 tumors, we curated 486 cases with SVs in PD-L1 and PD-L2 and observed consistent breakpoint patterns, or hotspots. Leveraging The Cancer Genome Atlas, we observed significant upregulation in PD-L1 expression and signatures for interferon signaling, macrophages, T cells, and immune cell proliferation in samples harboring PD-L1 or PD-L2 SVs. Retrospective review of 12 studies that identified patients with SVs in PD-L1 or PD-L2 revealed > 50% (52/71) response rate to PD-1 immunotherapy with durable responses. CONCLUSION: Our findings show that the 3'-UTR is frequently affected, and that SVs are associated with increased expression of ligands and immune signatures. Retrospective evidence from curated studies suggests this genomic alteration could help identify candidates for PD-1/PD-L1 immunotherapy. We expect these findings will better define PD-L1 and PD-L2 SVs in cancer and lend support for prospective clinical trials to target these alterations.

Case report: Robotically visualized and biopsy-confirmed peritoneal carcinomatosis as initial identification of metastatic prostate adenocarcinoma in a patient with a history of prostatic urethral lift.

Background: Peritoneal carcinomatosis is a particularly rare presentation of prostate cancer. Here we report a rare clinical case of surgically identified peritoneal carcinomatosis at the time of a planned robotic prostatectomy in a patient with a history of prostatic urethral lift procedure. Case presentation: A 72-year-old man, with a history of urinary retention managed with tamsulosin, presented to his local urologist. Prostatic urethral lift procedures were performed for symptom management. After a definitive uptrend in his prostate-specific antigen (PSA) values, a biopsy was obtained, which demonstrated prostate adenocarcinoma. On presurgical multidisciplinary review, it was presumed that he had very high-risk localized prostate cancer. However, upon initiation of robotically assisted laparoscopic radical prostatectomy (RALP), he was noted to have numerous punctate white plaques on the peritoneum; biopsy of these lesions confirmed metastatic disease-for which the patient was starting on triple therapy per the PEACE-1 trial. The PSA level responded appropriately, decreasing from 16.8 to 0.08. Genetic testing was performed and returned negative for any clinically significant mutations. Conclusion: Our patient, diagnosed with peritoneal carcinomatosis during a planned RALP, highlights the importance of vigilant laparoscopic exam prior to this prostatectomy. Multidisciplinary discussion is crucial for individualized and optimal treatment planning.

Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer.

PURPOSE: Bacillus Calmette-Guérin (BCG) is currently recommended as adjuvant therapy following complete transurethral resection of bladder tumor for high-risk nonmuscle-invasive bladder cancer (NMIBC). In response to the BCG shortage, gemcitabine plus docetaxel (Gem/Doce) has been utilized at our institution in the BCG-naïve setting. We report the outcomes of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce. MATERIALS AND METHODS: We retrospectively reviewed patients with BCG-naïve high-risk NMIBC treated with Gem/Doce from May 2013 through April 2021. Patients received 6 weekly intravesical instillations of sequential 1 gm gemcitabine and 37.5 mg docetaxel after complete transurethral resection of bladder tumor. Monthly maintenance of 2 years was initiated if disease-free at first followup. The primary outcome was recurrence-free survival. Survival was assessed with the Kaplan-Meier method, indexed from the first Gem/Doce instillation. Adverse events were reported using CTCAE (Common Terminology Criteria for Adverse Events) v5 (National Cancer Institute, Bethesda, Maryland). Differences were assessed with the log-rank test. RESULTS: There were 107 patients with a median followup of 15 months included in the analysis. Patients had high-risk characteristics including 47 with any carcinoma in situ and 55 with T1 disease. Recurrence-free survival was 89%, 85% and 82% at 6, 12 and 24 months, respectively. Recurrence rates were similar between patients with or without carcinoma in situ (p=0.42). No patient had disease progression or died of bladder cancer. One patient underwent cystectomy due to end-stage lower urinary tract symptoms. Overall survival was 84% at 24 months. There were 92 adverse events (1 ≥grade 3), and 4 (4%) patients were unable to receive a full induction course. CONCLUSIONS: Gem/Doce is an effective and well-tolerated therapy for BCG-naïve NMIBC. Further investigation is warranted.

Sequential Intravesical Valrubicin and Docetaxel for the Salvage Treatment of Non-Muscle-Invasive Bladder Cancer.

PURPOSE: Intravesical gemcitabine-docetaxel has emerged as an efficacious and well-tolerated salvage therapy for non-muscle-invasive bladder cancer. However, further rescue therapies are needed for subsequent recurrences or intolerance, particularly when cystectomy is refused or precluded. Valrubicin is a U.S. Food and Drug Administration-approved agent for bacillus Calmette-Guérin unresponsive disease, yet as monotherapy has demonstrated poor efficacy. We report our experience with sequential intravesical valrubicin and docetaxel as a rescue therapy for non-muscle-invasive bladder cancer. MATERIALS AND METHODS: We retrospectively identified all patients with recurrent non-muscle-invasive bladder cancer treated with valrubicin and docetaxel between April 2013 and June 2021. Patients received weekly sequential intravesical instillations of 800 mg valrubicin and 37.5 mg docetaxel for 6 weeks. If disease-free at first follow-up, monthly maintenance of 2 years was initiated. The primary outcome was recurrence-free survival, assessed using the Kaplan-Meier method. RESULTS: The analysis included 75 patients with median follow-up of 21 months (IQR: 13-37). Twelve patients with low-grade disease had a 73% recurrence-free survival at 2 years. Sixty-three patients with recurrent high-grade disease had a 38% 2-year high-grade recurrence-free survival. Forty-two (56%) patients had carcinoma in situ present; recurrence-free survival was similar for those with and without carcinoma in situ (P = .63). Two patients died of metastatic bladder cancer while 10 underwent cystectomy. Among patients with high-grade disease, overall, cancer-specific, and cystectomy-free survivals were 87%, 96%, and 84% at 2 years, respectively. Adverse events included bladder spasms (n = 18), urinary frequency (n = 10), and dysuria (n = 8). Two patients could not tolerate valrubicin and docetaxel induction. CONCLUSIONS: In a heavily pretreated population, our results suggest valrubicin and docetaxel is an effective rescue treatment for patients with recurrent non-muscle-invasive bladder cancer. Further prospective evaluation is needed.

Trends and practices for managing low-risk prostate cancer: a SEER-Medicare study.

BACKGROUND: Expectant management (EM) has been widely recommended for men with low-risk prostate cancers (PCa). We evaluated trends in EM and the sociodemographic and clinical factors associated with EM, initiating a National Comprehensive Cancer Network guideline-concordant active surveillance (AS) monitoring protocol, and switching from EM to active treatment (AT). METHODS: We used the SEER-Medicare database to identify men ages 66+ diagnosed with a low-risk PCa (PSA < 10 ng/mL, Gleason ≤ 6, stage ≤ T2a) in 2010-2013 with ≥1 year of follow-up. We used claims data to capture (1) PCa treatments, including surgical procedures, radiotherapy, and hormone therapy, and (2) AS monitoring procedures, including PSA tests and prostate biopsy. We defined EM as receiving no AT within 1 year of diagnosis. We used multivariable regression techniques to identify factors associated with EM, initiating AS monitoring, and switching to AT. RESULTS: During the study period, EM increased from 29.4% to 49.0%, p < 0.01. Age < 77, being married/partnered, non-Hispanic ethnicity, higher median ZIP code income, lower PSA levels, stage T1c, and more recent year of diagnosis were associated with EM. Nearly 39% of the EM cohort initiated AS monitoring; age <77, White race, being married/partnered, higher median ZIP code income, and lower PSA levels were associated with initiating AS. By three years after diagnosis, 21.3% of the EM cohort had switched to AT, usually after undergoing AS monitoring procedures. DISCUSSION: We found increasing uptake of EM over time, though over 50% still received AT. About 60% of EM patients did not initiate AS monitoring, even among those with life expectancy >10 years, implying that a substantial proportion was being managed by watchful waiting. AS monitoring was associated with switching to AT, suggesting that treatment decisions likely were based on cancer progression.

Intravesical sequential gemcitabine and docetaxel versus bacillus calmette-guerin (BCG) plus interferon in patients with recurrent non-muscle invasive bladder cancer following a single induction course of BCG.

INTRODUCTION: Repeat BCG induction remains an option for select non-muscle invasive bladder cancer (NMIBC) patients who fail initial therapy. Alternative salvage intravesical regimens such as Gemcitabine and Docetaxel (Gem/Doce) have been investigated. We aimed to compare the efficacy BCG plus interferon a-2b (BCG/IFN) and Gem/Doce in patients with recurrent NMIBC after a single prior BCG course. METHODS: The National Phase II BCG/IFN trial database and multi-institutional Gem/Doce database were queried for patients with recurrent NMIBC after one prior BCG induction course, excluding those with BCG unresponsive disease. Stabilized inverse probability treatment weighted survival curves were estimated using the Kaplan-Meier method and compared. Propensity scores were derived from a logistic regression model. The primary outcome was recurrence free survival (RFS); secondary outcomes were high-grade (HG) RFS and risk factors for treatment failure. RESULTS: We identified 197 BCG/IFN and 93 Gem/Doce patients who met study criteria. Patients receiving Gem/Doce were older and more likely to have HG disease, CIS, and persistent disease following induction BCG (all P < 0.01). After propensity score-based weighting, the adjusted 1- and 2-year RFS was 61% and 53% after BCG/IFN versus 68% and 46% after Gem/Doce (P = 0.95). Adjusted 1- and 2-year HG-RFS was 60% and 51% after BCG/IFN versus 63% and 42% after Gem/Doce (P = 0.68). Multivariable Cox regression revealed that Gem/Doce treatment was not associated with an increased risk of failure (HR = 0.97, P = 0.89) as compared to BCG/IFN. CONCLUSION: Patients with recurrent NMIBC after a single induction BCG failure and not deemed BCG unresponsive had similar oncologic outcomes with Gem/Doce and BCG/IFN in a post-hoc analysis. Additional prospective studies are needed.

Obesity induces limited changes to systemic and local immune profiles in treatment-naive human clear cell renal cell carcinoma.

Understanding the effects of obesity on the immune profile of renal cell carcinoma (RCC) patients is critical, given the rising use of immunotherapies to treat advanced disease and recent reports of differential cancer immunotherapy outcomes with obesity. Here, we evaluated multiple immune parameters at the genetic, soluble protein, and cellular levels in peripheral blood and renal tumors from treatment-naive clear cell RCC (ccRCC) subjects (n = 69), to better understand the effects of host obesity (Body Mass Index "BMI" ≥ 30 kg/m2) in the absence of immunotherapy. Tumor-free donors (n = 38) with or without obesity were used as controls. In our ccRCC cohort, increasing BMI was associated with decreased percentages of circulating activated PD-1+CD8+ T cells, CD14+CD16neg classical monocytes, and Foxp3+ regulatory T cells (Tregs). Only CD14+CD16neg classical monocytes and Tregs were reduced when obesity was examined as a categorical variable. Obesity did not alter the percentages of circulating IFNγ+ CD8 T cells or IFNγ+, IL-4+, or IL-17A+ CD4 T cells in ccRCC subjects. Of 38 plasma proteins analyzed, six (CCL3, IL-1ß, IL-1RA, IL-10, IL-17, and TNFα) were upregulated specifically in ccRCC subjects with obesity versus tumor-free controls with obesity. IGFBP-1 was uniquely decreased in ccRCC subjects with obesity versus non-obese ccRCC subjects. Immunogenetic profiling of ccRCC tumors revealed that 93% of examined genes were equivalently expressed and no changes in cell type scores were found in stage-matched tumors from obesity category II/III versus normal weight (BMI ≥ 35 kg/m2 versus 18.5-24.9 kg/m2, respectively) subjects. Intratumoral PLGF and VEGF-A proteins were elevated in ccRCC subjects with obesity. Thus, in ccRCC patients with localized disease, obesity is not associated with widespread detrimental alterations in systemic or intratumoral immune profiles. The effects of combined obesity and immunotherapy administration on immune parameters remains to be determined.

Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer.

PURPOSE: Rescue intravesical therapies for patients with bacillus Calmette-Guérin failure nonmuscle invasive bladder cancer remain a critical focus of ongoing research. Sequential intravesical gemcitabine and docetaxel therapy has shown safety and efficacy in 2 retrospective, single institution cohorts. This doublet has since been adopted as an intravesical salvage option at multiple institutions. We report the results of a multi-institutional evaluation of gemcitabine and docetaxel. MATERIALS AND METHODS: Each institution retrospectively reviewed all records of patients treated with intravesical gemcitabine and docetaxel for nonmuscle invasive bladder cancer between June 2009 and May 2018. Only patients with recurrent nonmuscle invasive bladder cancer and a history of bacillus Calmette-Guérin treatment were included in the analysis. If patients were disease-free after induction, maintenance was instituted at the treating physician's discretion. Posttreatment surveillance followed American Urological Association guidelines. Survival analysis was performed using the Kaplan-Meier method and risk factors for treatment failure were assessed with Cox regression models. RESULTS: Overall 276 patients (median age 73 years, median followup 22.9 months) received treatment. Nine patients were unable to tolerate a full induction course. One and 2-year recurrence-free survival rates were 60% and 46%, and high grade recurrence-free survival rates were 65% and 52%, respectively. Ten patients (3.6%) had disease progression on transurethral resection. Forty-three patients (15.6%) went on to cystectomy (median 11.3 months from induction), of whom 11 (4.0%) had progression to muscle invasion. Analysis identified no patient, disease or prior treatment related factors associated with gemcitabine and docetaxel failure. CONCLUSIONS: Intravesical gemcitabine and docetaxel therapy is well tolerated and effective, providing a durable response in patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin therapy. Further prospective study is warranted.

Quantitative Test-Retest Measurement of 68Ga-PSMA-HBED-CC in Tumor and Normal Tissue.

The PET radiotracer 68Ga-PSMA (prostate-specific membrane antigen)-HBED-CC (N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) shows potential as an imaging biomarker for recurrent and metastatic prostate cancer. The purpose of this study was to determine the repeatability of 68Ga-PSMA-HBED-CC in a test-retest trial in subjects with metastatic prostate adenocarcinoma. Methods: Subjects with metastatic prostate cancer underwent 2 PET/CT scans with 68Ga-PSMA-HBED-CC within 14 d (mean, 6 ± 4 d). Lesions in bone, nodes, prostate/bed, and visceral organs, as well as representative normal tissues (salivary glands and spleen), were segmented separately by 2 readers. Absolute and percentage differences in SUVmax and SUVmean were calculated for all test-retest regions. Repeatability was assessed using percentage difference, within-subject coefficient of variation (wCV), repeatability coefficient (RC), and Bland-Altman analysis. Results: Eighteen subjects were evaluated, 16 of whom demonstrated local or metastatic disease on 68Ga-PSMA-HBED-CC PET/CT. In total, 136 lesions were segmented in bone (n = 99), nodes (n = 27), prostate/bed (n = 7), and viscera (n = 3). The wCV for SUVmax was 11.7% for bone lesions and 13.7% for nodes. The RC was ±32.5% SUVmax for bone lesions and ±37.9% SUVmax for nodal lesions, meaning 95% of the normal variability between 2 measurements will be within these numbers, so larger differences are likely attributable to true biologic changes in tumor rather than normal physiologic or measurement variability. wCV in the salivary glands and spleen was 8.9% and 10.7% SUVmean, respectively. Conclusion: Repeatability measurements for PET/CT test-retests with 68Ga-PSMA-HBED-CC showed a wCV of 12%-14% SUVmax and an RC of ±33%-38% SUVmax in bone and nodal lesions. These estimates are an important aspect of 68Ga-PSMA-HBED-CC as a quantitative imaging biomarker. These estimates are similar to those reported for 18F-FDG, suggesting that 68Ga-PSMA-HBED-CC PET/CT may be useful in monitoring response to therapy.

Alpha-dystroglycan staining pattern and mortality in patients undergoing radical prostatectomy with lymph node positive prostate cancer.

INTRODUCTION: Dystroglycan (DG) is a cell surface receptor for extracellular matrix proteins involved in tissue mechanical stability and matrix organization. Initial work has demonstrated that alpha-DG expression is decreased in many types of adenocarcinoma, including prostate, and potentially associated with the development of metastatic disease. However, the consistency between prostate and lymph node alpha-DG staining has not been previously reported. In addition, identification of an immunohistochemical marker associated with prostate cancer grade, stage, need for adjuvant or salvage therapy and mortality would have potential clinical value. MATERIALS AND METHODS: Node positive, margin negative radical prostatectomy specimens at a single institution from 1982 to 2012 were reviewed and identified 35 prostate specimens, including 26 patients with available tissue from both the primary prostatectomy and lymph node specimens. The expression levels of the alpha-DG subunit were analyzed using immunohistochemistry and graded from 0 to 4. Survival was compared in different staining pattern groups. RESULTS: Strength of alpha-DG staining was found to be consistent between prostate and lymph node specimens (p < 0.004). The median overall survival was shorter in those without alpha-DG staining in the prostate compared to those with positive staining, but this difference was not statistically significant (13.2 years versus 19.4 years, p = 0.21). In addition, negative staining was associated with higher mean PSA, pathologic T stage, Gleason grade and the need for adjuvant or salvage therapy compared to positive group but none reached statistical significance (16.06 ng/mL versus 11.67 ng/mL, p = 0.79; 89% versus 68%, p = 0.38; 33.3% versus 23.1%, p = 0.66; 88.9% versus 76.9%, p = 0.44). CONCLUSIONS: DG expression by immunohistochemistry staining was consistent between prostate and metastatic lymph node specimens. In a small cohort of prostate cancer patients with margin negative but node positive disease, DG staining was not associated with Gleason grade or with overall mortality.

Why men with a low-risk prostate cancer select and stay on active surveillance: A qualitative study.

OBJECTIVE: Active surveillance (AS) is an increasingly utilized strategy for monitoring men with low-risk prostate cancer (PCa) that allows them to defer active treatment (AT) in the absence of cancer progression. Studies have explored reasons for selecting AS and for then switching to AT, but less is known about men's experiences being on AS. We interviewed men to determine the clinical and psychological factors associated with selecting and adhering to AS protocols. METHODS: We conducted semi-structured interviews with men with a low-risk PCa at two academic medical centers. Subjects had either been on AS for ≥ 1 year or had opted for AT after a period of AS. We used an iterative, content-driven approach to analyze the interviews and to identify themes. RESULTS: We enrolled 21 subjects, mean age 70.4 years, 3 racial/ethnic minorities, and 16 still on AS. Men recognized the favorable prognosis of their cancer (some had sought second opinions when initially offered AT), valued avoiding treatment complications, were reassured that close monitoring would identify progression early enough to be successfully treated, and trusted their urologists. Although men reported feeling anxious around the time of surveillance testing, those who switched to AT did so based only on evidence of cancer progression. CONCLUSIONS: Our selected sample was comfortable being on AS because they understood and valued the rationale for this approach. However, this highlights the importance of ensuring that men newly diagnosed with a low-risk PCa are provided sufficient information about prognosis and treatment options to make informed decisions.

Enhancing Identification and Management of Hospitalized Patients Who Are Malnourished: A Pilot Evaluation of Electronic Quality Improvement Measures.

Malnutrition in hospitalized patients has long been recognized as a contributor to poor patient outcomes; malnutrition often leads to higher costs of care. Thus, it is important to improve the identification of patients who are at risk for malnutrition or already malnourished and to initiate treatment to optimize outcomes. The Malnutrition Quality Improvement Initiative (MQii) is based on a dual-pronged approach consisting of a set of four electronic clinical quality measures and a Quality Improvement Toolkit that support delivery of high-quality malnutrition care by clinicians including nurses, registered dietitian nutritionists, and physicians. A large pilot hospital validated the four malnutrition electronic clinical quality measures (screening for nutrition risk, assessment, care plan, diagnosis), demonstrating their value in support of continuous quality improvement for hospital-based malnutrition care with the ultimate goal of better patient outcomes while reducing health care costs. FUNDING/SUPPORT: Publication of this supplement was supported by Abbott. The Academy of Nutrition and Dietetics does not receive funding for the MQii. Avalere Health's work to support the MQii was funded by Abbott.