Comparison of Multiparametric MRI-targeted and Systematic Biopsies for Detection of Cribriform and Intraductal Carcinoma Prostate Cancer.

Background Intraductal carcinoma (IDC) and invasive cribriform (Cr) subtypes of prostate cancer (PCa) are an indication of aggressiveness, but the evidence regarding whether MRI can be used to detect Cr/IDC-pattern PCa is contradictory. Purpose To compare the detection of Cr/IDC-pattern PCa at multiparametric MRI (mpMRI)-targeted biopsy versus systematic biopsy in biopsy-naive men at risk for PCa. Materials and Methods This study was a secondary analysis of a prospective randomized controlled trial that recruited participants with a clinical suspicion of PCa between April 2017 and November 2019 at five centers. Participants were randomized 1:1 to either the MRI arm or the systematic biopsy arm. Targeted biopsy was performed in participants with a Prostate Imaging Reporting and Data System score of at least 3. MRI features were recorded, and biopsy slides and prostatectomy specimens were reviewed for the presence or absence of Cr/IDC histologic patterns. Comparison of Cr/IDC patterns was performed using generalized linear mixed modeling. Results A total of 453 participants were enrolled, with 226 in the systematic biopsy arm (median age, 65 years [IQR, 59-70 years]; 196 biopsies available for assessment) and 227 in the mpMRI-targeted biopsy arm (median age, 67 years [IQR, 60-72 years]; 132 biopsies available for assessment). Identification of Cr/IDC PCa was lower in the systematic biopsy arm compared with the mpMRI arm (31 of 196 biopsies [16%] vs 33 of 132 biopsies [25%]; P = .01). No evidence of a difference in mean cancer core length (CCL) (11.3 mm ± 4.4 vs 9.7 mm ± 4.5; P = .09), apparent diffusion coefficient (685 µm2/sec ± 178 vs 746 µm2/sec ± 245; P = .52), or dynamic contrast-enhanced positivity (27 [82%] vs 37 [90%]; P = .33) for clinically significant PCa (csPCa) was observed between participants with or without Cr/IDC disease in the MRI arm. Cr/IDC-positive histologic patterns overall had a higher mean CCL compared with Cr/IDC-negative csPCa (11.1 mm ± 4.4 vs 9.2 mm ± 4.1; P = .009). Conclusion MRI-targeted biopsy showed increased detection of Cr/IDC histologic patterns compared with systematic biopsy. Clinical trial registration no. NCT02936258 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Scialpi and Martorana in this issue.

The "Ins and Outs" of Prostate Specific Membrane Antigen (PSMA) as Specific Target in Prostate Cancer Therapy.

Prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with metastasis, progression, and androgen independence. Because of its specificity, PSMA is a major target of prostate cancer therapy; however, detectable levels of PSMA are also found in other tissues, especially in salivary glands and kidney, generating bystander damage of these tissues. Antibody target therapy has been used with relative success in reducing tumor growth and prostate specific antigen (PSA) levels. However, since antibodies are highly stable in plasma, they have prolonged time in circulation and accumulate in organs with an affinity for antibodies such as bone marrow. For that reason, a second generation of PSMA targeted therapeutic agents has been developed. Small molecules and minibodies have had promising clinical trial results, but concerns about their specificity had arisen with side effects due to accumulation in salivary glands and kidneys. Herein we study the specificity of small molecules and minibodies that are currently being clinically tested. We observed a high affinity of these molecules for PSMA in prostate, kidney and salivary gland, suggesting that their effect is not prostate specific. The search for specific prostate target agents must continue so as to optimally treat patients with prostate cancer, while minimizing deleterious effects in other PSMA expressing tissues.

Is the Unequal COVID-19 Burden in Canada Due to Unequal Levels of Citizen Discipline across Provinces?

The unequal burden of the coronavirus disease 2019 (COVID-19) crisis (e.g., in terms of infection and death rates) across Canadian provinces is important and puzzling. Some have speculated that differences in levels of citizen compliance with public health preventive measures are central to understanding cross-provincial differences in pandemic-related health outcomes. However, no systematic empirical test of this hypothesis has been conducted. In this research, we make use of an exceptionally large dataset that includes 23 survey waves (N = 22,610) fielded in Canada across 12 months (April 2020-April 2021) to answer the question "Is there evidence of substantial cross-provincial differences in citizen compliance with basic public health measures designed to prevent the spread of infection?" We find that regional differences in self-reported behaviour are few and very modest, suggesting that interprovincial differences in COVID-19-related health outcomes have little to do with differences in citizen compliance, at least in the first year of the pandemic. These results have important implications. Although it is crucial that we continue to study regional variations related to the COVID-19 burden, public health agency officials, pundits, and politicians should be cautious when musing about the role of citizen compliance as the primary explanation of interprovincial pandemic health outcomes.

L'inégalité des effets de la maladie du coronavirus 2019 (COVID -19) à travers les provinces canadiennes (notamment quant au taux d'infection et de décès) est importante et intrigante. Certains ont postulé que pour mieux comprendre les écarts dans les effets de la pandémie entre les provinces, il faudrait étudier les écarts dans l'application, par les citoyens, des mesures préventives de santé publique. Toutefois, aucun test empirique systématique n'a été effectué pour valider ce postulat. Dans cette recherche, nous utilisons un base de données de taille exceptionnelle, comprenant 23 vagues d'enquêtes (N= 22,610) réalisées sur 12 mois (avril 2020- avril 2021) pour répondre à la question « Existe-t-il une preuve de différences considérables entre les provinces dans l'application par les citoyens des mesures sanitaires de base en vue de prévenir la transmission de l'infection? ¼ Nous constatons que les différences régionales dans le comportement autodéclaré sont très faibles, ce qui veut dire que l'écart des effets de la COVID-19 sur la santé entre les provinces n'avait pas grand-chose à voir avec l'application des mesures par les citoyens, du moins pendant la première année de la pandémie. Ces résultats ont des implications importantes. Même s'il est capital de continuer à étudier les variations régionales reliées au fléau de la COVID-19, les autorités publiques de la santé, les spécialistes et les politiciens, doivent être vigilants quand ils présentent l'application des mesures par les citoyens comme étant la première explication de l'écart des effets sur la santé entre les provinces.

Abdominal visceral perforation by buried peritoneal dialysis catheters: Cause or coincidence?

Delayed visceral organ perforations after PD catheter insertions are extremely rare. We report two patients who presented with asymptomatic visceral perforation from their buried PD catheters. Five months after a laparoscopic buried PD catheter insertion in a 92-year-old man PD was initiated; bile and bowel contents were noted in the PD effluent. He subsequently expired (from pneumonia) to autopsy revealed the PD catheter within the small bowel. Despite this perforation, there was no evidence of peritonitis, inflammation, nor any bowel content within the peritoneal cavity. A second case was observed 2.5 months after an uncomplicated laparoscopic buried PD catheter insertion in a 60-year-old woman. PD was attempted; the patient had an immediate urge to void. MRI revealed the presence of the PD catheter within her bladder. She underwent PD catheter revision the next day with repair of bladder perforation and ultimately successfully initiated PD. Since the perforations did not occur at the time of catheter placement, we believe that the catheter eroded into a viscus, perhaps related to the lack of a fluid at the catheter - viscus interface. The diagnosis of delayed visceral organ perforation following buried PD catheter insertion may be delayed because the catheter is not immediately used.

Primary amyloidosis of the bladder; a mimicker of bladder cancer.

Amyloidosis is a protein folding disorder characterized by the deposition of fibrillar proteins into solid organs or tissues. Primary localized amyloidosis of the bladder is very rare and can mimic bladder cancer in its presentation with hematuria, lower urinary tract symptoms or a mass on imaging. A case of localized amyloidosis of the bladder in a 48-year-old man with painless gross hematuria and evidence of bladder mass on ultrasound is presented. Amyloidosis is a rare but important non-malignant process of the bladder. We present a review of the literature and suggestions for management of this rare bladder disease.

Perineural invasion on biopsy is associated with upstaging at radical prostatectomy in Gleason score 3 + 4 = 7 prostate cancer.

This study assesses if perineural invasion (PNI) detected on biopsy with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) is associated with upstaging/upgrading of disease after radical prostatectomy (RP). 154 patients with GS 3 + 4 = 7 PCa diagnosed from biopsy who underwent RP were assessed for PNI. The percentage of biopsy sites with PNI (%PNI) was also calculated. Pattern 4 morphologies (ill-defined glands [IDG], fused, cribriform, and glomerulations) were also assessed. Clinical information, GS and stage after RP were retrieved from the medical records. 45 % (69/154) of patients were upstaged (≥pT3) and 29 % (44/154) were upgraded to GS >3 + 4 = 7 after RP. 37 % (57/154) of patients had PNI which was associated with upstaging (RR 1.4; P = 0.04) but not upgrading (RR 0.9; P = 0.7). There was higher %PNI in upstaged patients (12.1 % ± 1.8 vs. 7.1 % ± 1.5, P = 0.03) with a significant correlation between %PNI and ≥pT3 (r = 0.178, P = 0.027). After multivariate analysis, only cribriform formations were significantly associated with upstaging (P = 0.009). The presence of PNI in biopsies with GS 3 + 4 = 7 PCa is associated with upstaging at RP but is a weaker predictor of ≥pT3 disease than cribriform morphology.

Nested and microcystic variants of urothelial carcinoma displaying immunohistochemical features of basal-like urothelial cells: an immunohistochemical and histopathogenetic study.

Nested/microcystic (NV/MV) urothelial carcinoma (UC) variants are associated with mild cytologic atypia and commonly present at high-stage disease. The histopathogenesis is investigated using urothelial basal cell markers. Archival 14 NV/MV and three inverted papilloma (IP) were immunostained for CD44, cytokeratin 5 (CK5), CK34bE12 and p63. Twenty consecutive cases of invasive high-grade UC including 14 superficial and 6 muscle-invasive UC cases were used as control. Immunostaining was scored as high for staining of full or more than 50% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity and negative reactivity. All 14 NV/MV, 3 IP and 6 control cases showed a high score of immunoreactivity for CK5, CD44, CK34bE12 and focally for p63. The remaining control cases showed a high score of immunoreactivity for CK34bE12, while negative or low for CK5, CD44 and p63. In conclusion, immunoreactivity CK5 and CD44 commonly immunostained NV/MV and some invasive high grade UC. Other basal cell markers (CK34bE12 and p63) appear to be non specific or non sensitive. NV and MV and some UC likely represent a subset of UC displaying immunohistochemical features of urothelial basal cells. They had tendency of endophytic growth and early invasion despite the innocuous cytologic appearance.

Quantifying the Impact of Cancer on the Viscoelastic Properties of the Prostate Gland using a Quasi-Linear Viscoelastic Model.

Pathological disorders can alter the mechanical properties of biological tissues, and studying such changes can help to better understand the disease progression. The prostate gland is no exception, as previous studies have shown that cancer can affect its mechanical properties. However, most of these studies have focused on the elastic properties of the tissue and have overlooked the impact of cancer on its viscous response. To address this gap, we used a quasi-linear viscoelastic model to investigate the impact of cancer on both the elastic and viscous characteristics of the prostate gland. By comparing the viscoelastic properties of segments influenced by cancer and those unaffected by cancer in 49 fresh prostates, removed within two hours after prostatectomy surgery, we were able to determine the influence of cancer grade and tumor volume on the tissue. Our findings suggest that tumor volume significantly affects both the elastic modulus and viscosity of the prostate (p-value less than 2%). Specifically, we showed that cancer increases Young's modulus and shear relaxation modulus by 20%. These results have implications for using mechanical properties of the prostate as a potential biomarker for cancer. However, developing an in vivo apparatus to measure these properties remains a challenge that needs to be addressed in future research. STATEMENT OF SIGNIFICANCE: This study is the first to explore how cancer impacts the mechanical properties of prostate tissues using a quasi-linear viscoelastic model. We examined 49 fresh prostate samples collected immediately after surgery and correlated their properties with cancer presence identified in pathology reports. Our results demonstrate a 20% change in the viscoelastic properties of the prostate due to cancer. We initially validated our approach using tissue-mimicking phantoms and then applied it to differentiate between cancerous and normal prostate tissues. These findings offer potential for early cancer detection by assessing these properties. However, conducting these tests in vivo remains a challenge for future research.

Detection and resection of carcinoma in situ of the bladder: Implications for clinical trial design.

INTRODUCTION: The path to approval of novel therapeutics for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) requires demonstration of efficacy in eradicating carcinoma in situ (CIS), as determined by cytology, white light cystoscopy and only sometimes mandatory re-biopsy. This paradigm is based on the premise that CIS, in contrast to papillary tumors, cannot be completely resected. We aimed to determine the accuracy of CIS by standard means and the rate at which CIS may be eradicated by transurethral bladder tumor resection (TURBT). METHODS: We performed a retrospective analysis of consecutive patients who underwent radical cystectomy (RC) for high risk NMIBC or muscle invasive bladder cancer (MIBC) between 2005 and 2019 in a tertiary academic center. The concordance in the presence of CIS in matched TURBT and RC samples was calculated. RESULTS: Complete pathologic information was available for 816 patients with urothelial carcinoma. CIS was detected at TURBT in 354 (43.4%) patients (64.0% NMIBC, 32.3% MIBC) and at RC in 436 (53.4%) patients (64.7% NMIBC, 47.4% MIBC). CIS was missed by TURBT in 199 (45.6%) of those cases (NMIBC 25.4%, MIBC 60.6%). CIS detected on TURBT was not found in the RC specimen in 33.1% (117/354) of cases. Lack of prospective bladder mapping and central pathology review are limitations. CONCLUSION: Our results suggest that TURBT is inaccurate in detecting CIS. The absence of CIS in the RC specimen after detection in the matched TURBT specimen suggests that CIS may be completely resected by TURBT in a proportion of patients. These factors need to be considered in the design of clinical trials in patients with NMIBC. The use of random biopsies or enhanced cystoscopy could improve the accuracy of CIS detection, but the former is associated with patient morbidity and randomization would alleviate concern about these variables impacting clinical trial outcomes.

Stimulated Raman histology as a method to determine the adequacy of renal mass biopsy and identify malignant subtypes of renal cell carcinoma.

INTRODUCTION: Renal tumor biopsy requires adequate tissue sampling to aid in the investigation of small renal masses. In some centers the contemporary nondiagnostic renal mass biopsy rate may be as high as 22% and may be as high as 42% in challenging cases. Stimulated Raman Histology (SRH) is a novel microscopic technique which has created the possibility for rapid, label-free, high-resolution images of unprocessed tissue which may be viewed on standard radiology viewing platforms. The application of SRH to renal biopsy may provide the benefits of routine pathologic evaluation during the procedure, thereby reducing nondiagnostic results. We conducted a pilot feasibility study, to assess if renal cell carcinoma (RCC) subtypes may be imaged and to see if high-quality hematoxylin and eosin (H&E) could subsequently be generated. METHODS/MATERIALS: An 18-gauge core needle biopsy was taken from a series of 25 ex vivo radical or partial nephrectomy specimens. Histologic images of the fresh, unstained biopsy samples were obtained using a SRH microscope using 2 Raman shifts: 2,845 cm-1 and 2,930 cm-1. The cores were then processed as per routine pathologic protocols. The SRH images and hematoxylin and eosin (H&E) slides were then viewed by a genitourinary pathologist. RESULTS: The SRH microscope took 8 to 11 minutes to produce high-quality images of the renal biopsies. Total of 25 renal tumors including 1 oncocytoma, 3 chromophobe RCC, 16 clear cells RCC, 4 papillary RCC, and 1 medullary RCC were included. All renal tumor subtypes were captured, and the SRH images were easily differentiated from adjacent normal renal parenchyma. High quality H&E slides were produced from each of the renal biopsies after SRH was completed. Immunostains were performed on selected cases and the staining was not affected by the SRH image process. CONCLUSION: SRH produces high quality images of all renal cell subtypes that can be rapidly produced and easily interpreted to determine renal mass biopsy adequacy, and on occasion, may allow renal tumor subtype identification. Renal biopsies remained available to produce high quality H&E slides and immunostains for confirmation of diagnosis. Procedural application has promise to decrease the known rate of renal mass nondiagnostic biopsies, and application of convolutional neural network methodology may further improve diagnostic capability and increase utilization of renal mass biopsy among urologists.

The BC Generations Project as a Tumor Tissue Resource for Cancer Research.

Population-based cohort studies can be a resource for tumor specimens, annotated with demographic, lifestyle, and health history data, that support innovative studies of cancer. Our aim was to establish and test a process for accessing tumor samples, held at pathology laboratories around British Columbia (BC), for participants of the BC Generations Project (BCGP). Through the BC Cancer Registry, we identified pathology reports for 1100 (93%) of the 1180 incident solid cancer cases diagnosed in BCGP as of 2019. Using manually abstracted data from the reports, we successfully retrieved 183 (92%) of the 200 formalin-fixed, paraffin-embedded (FFPE) blocks (breast, lung, bladder, and pancreas cancer cases) that we requested from pathology laboratories. No important differences in retrieval rates by cancer site, sample location (Greater Vancouver vs. Outside Greater Vancouver), sample type (biopsy vs. excision) or year of diagnosis were identified. A text mining solution recently implemented by the Registry will allow us to automate the process for data abstraction and should capture pathology reports for 100% of all newly diagnosed BCGP cancer cases moving forward. This will further enhance the utility of BCGP as a high-quality tumor tissue research resource.

Unexpected diagnosis of metastatic breast carcinoma in an endomyocardial biopsy done for cardiac allograft rejection evaluation.

We report a case of a 75-year-old female post orthotopic heart transplantation, who presented to the emergency department with a six-week history of shortness of breath, hand tremor and ultimately delirium. She had lobular breast carcinoma more than 5 years prior to her heart transplant, treated by lumpectomy followed by anthracycline based chemotherapy. The reason for her heart transplant was heart failure that was suspected to be from anthracycline cardiomyopathy, however, her explanted heart actually showed cardiac sarcoidosis. She was placed on long-term immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. Two years after her heart transplant, she underwent bilateral mastectomies for recurrent breast cancer. Her neurological workup, including brain imaging (CT, MRI, LP and EEG) did not show any structural abnormalities, ischemia, mass or neurosarcoidosis as cause for delirium. Tacrolimus was held due to renal dysfunction and hemolytic anemia, and then she developed signs of right heart failure so an endomyocardial biopsy was carried out for suspected allograft rejection. The biopsy did not show any evidence of cellular or antibody medicated rejection; however, it demonstrated infiltration by bland appearing cells with signet ring morphology cells many of which showed intracytoplasmic mucin. The cells were strongly positive with cytokeratins AE1/3, CK7 and mammaglobin. The morphology and immunoprofile were consistent with metastatic lobular breast carcinoma and this was thought to be the cause of her clinical presentation with delirium, hemolytic anemia and renal dysfunction as a paraneoplastic syndrome.

Citizens' Willingness to Support New Taxes for COVID-19 Measures and the Role of Trust.

The COVID-19 public health pandemic has seen governments spend trillions of dollars to limit the spread of the COVID-19 virus as well as to soften the economic blow from the shutting down of national economies. Subsequent budget shortfalls raise the question of how governments will pay for the direct and indirect costs associated with the COVID-19 pandemic. In this article, we study the public's willingness to contribute through paying a new tax, with a focus on Canada. We find that both generalized social and political trust are associated with a greater willingness to support a COVID-related tax and that generalized social trust, in particular, attenuates the negative effect of an experimentally manipulated, specified level of tax burden on policy support. These findings entail important implications for the public opinion and tax policies literature, as well as for policy makers. RELATED ARTICLES: Gainous, Jason, Stephen C. Craig, and Michael D. Martinez. 2008. "Social Welfare Attitudes and Ambivalence about the Role of Government." Politics & Policy 36 (6): 972-1004. https://doi.org/10.1111/j.1747-1346.2008.00147 Shock, David R. 2013. "The Significance of Opposition Entrepreneurs on Local Sales Tax Referendum Outcomes." Politics & Policy 41 (4): 588-614. https://doi.org/10.1111/polp.12028 Wagle, Udaya R. 2013. "The Heterogeneity Politics of the Welfare State: Changing Population Heterogeneity and Welfare State Policies in High-Income OECD Countries, 1980-2005." Politics & Policy 41 (6): 947-984. https://doi.org/10.1111/polp.12053.

VOLUNTAD DE LOS CIUDADANOS PARA APOYAR NUEVOS IMPUESTOS PARA LAS MEDIDAS COVID­19 Y EL PAPEL DE LA CONFIANZA: La pandemia de salud pública COVID­19 hizo que los gobiernos gastaran billones de dólares para limitar la propagación del virus COVID­19, así como para suavizar el golpe económico del cierre de las economías nacionales. Los posteriores déficits presupuestarios plantean la cuestión de cómo pagarán los gobiernos los costos directos e indirectos asociados con la pandemia de COVID­19. En este documento, estudiamos la disposición del público a contribuir mediante el pago de un nuevo impuesto. Encontramos que tanto la confianza social como política generalizada se asocian con una mayor disposición a apoyar un impuesto relacionado con COVID y que la confianza social generalizada en particular atenúa el efecto negativo de un nivel especificado de carga tributaria manipulado experimentalmente sobre el apoyo a las políticas. Estos hallazgos tienen implicaciones importantes para la opinión pública y la literatura sobre políticas fiscales, y también para los responsables de la formulación de políticas.

A guilt-free strategy increases self-reported non-compliance with COVID-19 preventive measures: Experimental evidence from 12 countries.

Studies of citizens' compliance with COVID-19 preventive measures routinely rely on survey data. While such data are essential, public health restrictions provide clear signals of what is socially desirable in this context, creating a potential source of response bias in self-reported measures of compliance. In this research, we examine whether the results of a guilt-free strategy recently proposed to lessen this constraint are generalizable across twelve countries, and whether the treatment effect varies across subgroups. Our findings show that the guilt-free strategy is a useful tool in every country included, increasing respondents' proclivity to report non-compliance by 9 to 16 percentage points. This effect holds for different subgroups based on gender, age and education. We conclude that the inclusion of this strategy should be the new standard for survey research that aims to provide crucial data on the current pandemic.

Evaluation of bacterial contamination and control methods in soluble metalworking fluids.

In the United States, 1.2 million workers are exposed to metalworking fluids. During operations, aerosols are produced and airborne contaminants can be inhaled. Although biocides are used to control the bacterial content of metalworking fluids, they can create health-related problems, and their efficiency remains to be proved. The objectives of this project were (1) to verify whether rigorous cleaning according to a standard protocol could reduce microbial contamination and (2) whether the use of biocides with different spectra could reduce the bacterial population. Four similar machines producing similar components were evaluated; a specific treatment was applied to each machine. The machine used as a control (1) was thoroughly cleaned prior to sampling, (2) did not undergo any major cleaning afterward, and (3) was operated without the use of any biocide. A major cleaning is a protocol described and recommended by the fluid manufacturer and was performed on the three other machines, two of which were subsequently treated with biocides weekly. Fluid samples from the four lathes were collected weekly during a 6-month period, and total bacterial and cultivable Gram-negative bacteria were analyzed for each sample. Major cleaning of the machines (120-4) did not significantly reduce the concentration of bacteria in the cutting fluids when compared with the control machine (120-3), which had not undergone major cleaning. The concentrations of total bacteria were in the 10(6) CFU/mL range for these two lathes; however, a reduction in the total number of fluid changes was observed for this machine. Bacterial flora in the cutting fluids was significantly controlled with the use of biocides. Bacteria concentrations were in the 10(3)-10(5) CFU/mL range for the lathes with the use of biocides. Since thorough cleaning is insufficient and biocides are recognized as being responsible for some worker health problems, other avenues for controlling bacterial flora in cutting fluids should be evaluated to reduce worker exposure to their bacterial contaminants.

Chemical Stability of Reconstituted Sincalide in Sterile Water Under 2 Different Storage Conditions.

This study aimed to evaluate the chemical stability of sincalide at 2 common storage conditions-room temperature and refrigeration-in an attempt to simulate the conditions faced during centralized reconstitution and subsequent distribution to regional clinical facilities. Sincalide is a peptide hormone product administered parenterally as an aid for diagnostic imaging of hepatobiliary conditions. With an estimated postreconstitution shelf-life of 8 h (updated by the manufacturer in 2014 with limited supporting data) and frequent shortages due to an intermittent supply, there is both clinical and economic value in the experimental determination of the true chemical stability of this agent. Methods: Sincalide was reconstituted and stored at both temperatures (n = 4 each), and samples were collected at predetermined time points. A validated high-performance liquid chromatography analytic method was used for quantification of the active ingredient in these samples. Results: Little to no chemical degradation of sincalide was observed for the duration of study, over 8 d, after reconstitution and storage at room temperature. A trend toward a cyclic fluctuation in concentration was also shared among all samples. A similar trend toward little to no chemical degradation and cyclic pattern was observed for the duration of study, over 8 d, after reconstitution and storage in refrigeration. Conclusion: This study supports that from a chemical standpoint, sincalide may potentially be used up to at least 8 d after reconstitution with sterile water, thus providing convenience and cost-saving benefits to medical institutions using the product. The findings of this study, however, warrant microbial testing over this storage duration before any recommendations for extended use can be made.

Evaluation of individual and cumulative sites of extrarenal tumor invasion in pT3a clear cell renal cell carcinoma.

INTRODUCTION: The Tumor-Node-Metastasis classification of renal cell carcinoma (RCC) for pT3a tumors includes sinus fat invasion (SFI), perinephric fat invasion (PFI), renal vein invasion (RVI), and/or pelvicaliceal system invasion (PSI). The purpose of this study was to determine the association between these patterns of invasion (assessed individually and cumulatively) with the development of metastases and cancer-specific mortality (CSM). MATERIALS AND METHODS: We identified 160 patients who underwent radical nephrectomy for pT3a clear cell RCC between 2011 and 2017. The association between individual patterns of invasion and metastases and cancer-specific survival were evaluated with multivariate logistic regression. Cox Hazard proportion ratios and Kaplan-Meier survival curves were generated for patterns of invasion (assessed individually and cumulatively). RESULTS: The number of individual invasive patterns was as follows: 97/160 (61%) presented with RVI, 91/160 with SFI (57%), 62/160 with PFI (39%), and 24/160 (15%) with PSI. At multivariate analysis, both PFI and RVI were associated with metastases (P < 0.001 and 0.028, respectively). PFI (hazard ratio [HR] 4.12, 95% confidence interval [CI] 2.14-7.92; P < 0.001), RVI (HR 2.44, 95% CI 1.18-5.01; P = 0.015), SFI (HR 2.13, 95% CI 1.05-4.34; P = 0.036) had higher CSM, while PSI (HR 1.43, 95% CI 0.65-3.16; p = 0.38) did not show increased CSM. Furthermore, cumulative analysis showed that multiple invasive patterns resulted in worse CSM (p < 0.001). CONCLUSIONS: In our study, PFI was associated with the most aggressive behavior while PSI was the most indolent. Furthermore, the presence of more than one pattern of invasion was associated with worse CSM. These results indicate that reporting of the individual location and cumulative amount of pT3a patterns of invasion in clear cell RCC is clinically relevant.

Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement on Heart Transplantation: Patient Eligibility, Selection, and Post-Transplantation Care.

Significant practice-changing developments have occurred in the care of heart transplantation candidates and recipients over the past decade. This Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement provides evidence-based, expert panel recommendations with values and preferences, and practical tips on: (1) patient selection criteria; (2) selected patient populations; and (3) post transplantation surveillance. The recommendations were developed through systematic review of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The evolving areas of importance addressed include transplant recipient age, frailty assessment, pulmonary hypertension evaluation, cannabis use, combined heart and other solid organ transplantation, adult congenital heart disease, cardiac amyloidosis, high sensitization, and post-transplantation management of antibodies to human leukocyte antigen, rejection, cardiac allograft vasculopathy, and long-term noncardiac care. Attention is also given to Canadian-specific management strategies including the prioritization of highly sensitized transplant candidates (status 4S) and heart organ allocation algorithms. The focus topics in this position statement highlight the increased complexity of patients who undergo evaluation for heart transplantation as well as improved patient selection, and advances in post-transplantation management and surveillance that have led to better long-term outcomes for heart transplant recipients.

Oncocytic renal cell carcinoma with immunohistochemical properties of renal oncocytoma.

Renal oncocytoma (RO) is a characteristic benign renal tumor. The existence of malignant RO is controversial and anecdotal, partly due to a lack of specific markers for RO. With recent advances in immunohistochemistry, RO can be distinguished from other renal neoplasms with routine stains and with the aid of immunostaining. We report two cases of renal neoplasms with similar histopathological appearances. They were characterized by oncocytic cytoplasm, numerous intra-cytoplasmic vacuoles, uniform round to oval hyperchromatic nuclei with remarkably thick nuclear membranes and prominent nucleoli. The tumor cells were closely packed and disposed in an alveolar pattern. The neoplastic cells were diffusely reactive for CD117 and progesterone receptor, and diffusely or focally reactive for cytokeratin AE1/AE3, and focally reactive for cytokeratin 7, CD10, and racemase. The cells were non-reactive for renal cell carcinoma (RCC) antigen, vimentin, S100, and neuroendocrine markers. One tumor showed lymph node metastasis. Due to the remarkable cytological atypia, lymph node metastasis, and similar immunological features of RO, these two tumors likely represent a distinct subtype of RCC related to RO.