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BACKGROUND: In-field or in-margin recurrence after partial gland cryosurgical ablation (PGCA) of prostate cancer (PCa) remains a limitation of the paradigm. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real time, label-free, high-resolution microscopic images of unprocessed, un-sectioned tissue which can be interpreted by humans or artificial intelligence (AI). We evaluated surgical team and AI interpretation of SRH for real-time pathologic feedback in the planning and treatment of PCa with PGCA. METHODS: About 12 participants underwent prostate mapping biopsies during PGCA of their PCa between January and June 2022. Prostate biopsies were immediately scanned in a SRH microscope at 20 microns depth using 2 Raman shifts to create SRH images which were interpreted by the surgical team intraoperatively to guide PGCA, and retrospectively assessed by AI. The cores were then processed, hematoxylin and eosin stained as per normal pathologic protocols and used for ground truth pathologic assessment. RESULTS: Surgical team interpretation of SRH intraoperatively revealed 98.1% accuracy, 100% sensitivity, 97.3% specificity for identification of PCa, while AI showed a 97.9% accuracy, 100% sensitivity and 97.5% specificity for identification of clinically significant PCa. 3 participants' PGCA treatments were modified after SRH visualized PCa adjacent to an expected MRI predicted tumor margin or at an untreated cryosurgical margin. CONCLUSION: SRH allows for accurate rapid identification of PCa in PB by a surgical team interpretation or AI. PCa tumor mapping and margin assessment during PGCA appears to be feasible and accurate. Further studies evaluating impact on clinical outcomes are warranted.
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The aim of this study was to present a framework for clinicians to use when discussing electronic cigarette (e-cigarette) use and its association with pre-diabetes. A communication tool was designed using evidence-based strategies from the academic literature. A four-step framework is presented, which includes: step (1) helping patients to understand the association between e-cigarette use and pre-diabetes; step (2) the synergistic health impacts of e-cigarette use and pre-diabetes; step (3) management of diabetes-related lifestyle factors; and step (4) stages of change assessment related to e-cigarette reduction. This communication tool provides support for clinicians to discuss the risk of pre-diabetes associated with e-cigarette use. Moving forward, implementation and evaluation of this model are needed.
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Sistemas Eletrônicos de Liberação de Nicotina , Estado Pré-Diabético , Vaping , Humanos , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/etiologia , Comunicação , Estilo de VidaRESUMO
INTRODUCTION: Delay between targeted prostate biopsy (PB) and pathologic diagnosis can lead to a concern of inadequate sampling and repeated biopsy. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real-time, label-free, high-resolution microscopic images of unprocessed, unsectioned tissue. This technology holds potential to decrease the time for PB diagnosis from days to minutes. We evaluated the concordance of pathologist interpretation of PB SRH as compared with traditional hematoxylin and eosin (H&E) stained slides. METHODS: Men undergoing prostatectomy were included in an IRB-approved prospective study. Ex vivo 18-gauge PB cores, taken from prostatectomy specimen, were scanned in an SRH microscope (NIO; Invenio Imaging) at 20 microns depth using two Raman shifts: 2845 and 2930 cm-1 , to create SRH images. The cores were then processed as per normal pathologic protocols. Sixteen PB containing a mix of benign and malignant histology were used as an SRH training cohort for four genitourinary pathologists, who were then tested on a set of 32 PBs imaged by SRH and processed by traditional H&E. Sensitivity, specificity, accuracy, and concordance for prostate cancer (PCa) detection on SRH relative to H&E were assessed. RESULTS: The mean pathologist accuracy for the identification of any PCa on PB SRH was 95.7%. In identifying any PCa or ISUP grade group 2-5 PCa, a pathologist was independently able to achieve good and very good concordance (κ: 0.769 and 0.845, respectively; p < 0.001). After individual assessment was completed a pathology consensus conference was held for the interpretation of the PB SRH; after the consensus conference the pathologists' concordance in identifying any PCa was also very good (κ: 0.925, p < 0.001; sensitivity 95.6%; specificity 100%). CONCLUSION: SRH produces high-quality microscopic images that allow for accurate identification of PCa in real-time without need for sectioning or tissue processing. The pathologist performance improved through progressive training, showing that ultimately high accuracy can be obtained. Ongoing SRH evaluation in the diagnostic and treatment setting hold promise to reduce time to tissue diagnosis, while interpretation by convolutional neural network may further improve diagnostic characteristics and broaden use.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Estudos Prospectivos , Biópsia , Neoplasias da Próstata/patologia , ProstatectomiaRESUMO
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.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Amarelo de Eosina-(YS) , Hematoxilina , Biópsia/métodos , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos , Biópsia com Agulha de Grande CalibreRESUMO
BACKGROUND: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation. OBJECTIVE: To develop a prediction model for urinary tract cancer in patients referred with haematuria. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism. RESULTS AND LIMITATIONS: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy. CONCLUSIONS: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation. PATIENT SUMMARY: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation.
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Neoplasias Renais , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Masculino , Neoplasias Urológicas/complicações , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/epidemiologia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
BACKGROUND: Despite years of slow progress, muscle invasive bladder cancer (MIBC) is finally entering the era of molecularly guided targeted therapy. However, tumor heterogeneity is high in MIBC and may impact treatment response and resistance. The objective of this review is to dissect recent insights into inter- and intratumor heterogeneity (ITH) in MIBC, with emphasis on the clinical implications of this heterogeneity for biomarker-driven strategies and the development of new therapies. METHODS: A nonsystematic review was performed in PubMed and EMBASE using the terms "tumor heterogeneity" and "bladder cancer." RESULTS: Intertumor heterogeneity, as reflected by different clinical phenotypes in different patients, has been partially explained with next generation sequencing and other molecular profiling technologies. RNA-based molecular subtyping, for example, provides a classification of MIBC into distinct categories that can be used for further molecular analysis, biomarker discovery, risk stratification, and treatment selection. Molecular subtyping and specific genomic alterations, especially in DNA damage repair genes, may help explain why some patients respond better to systemic chemotherapy and immunotherapy. Conversely, spatial and temporal ITH threaten to confound attempts to target specific molecular lesions since not all tumor cells within a patient may carry the relevant lesion. Improved understanding and management of ITH is required for the most effective use of biomarker-driven targeted therapies. CONCLUSION: Strategies to assess and overcome intertumor and ITH in MIBC will be critical steps toward realizing the objectives of precision oncology. Novel techniques such as analysis of circulating tumor DNA and single cell sequencing are likely to revolutionize our understanding of tumor heterogeneity.
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Neoplasias da Bexiga Urinária , Biomarcadores , Biomarcadores Tumorais/genética , Humanos , Músculos/patologia , Invasividade Neoplásica , Medicina de Precisão , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/terapiaRESUMO
OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer.
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Neoplasias Renais/diagnóstico , Neoplasias Ureterais/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Feminino , Hematúria/etiologia , Humanos , Neoplasias Renais/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Encaminhamento e Consulta , Neoplasias Ureterais/complicações , Neoplasias da Bexiga Urinária/complicaçõesRESUMO
INTRODUCTION: Postoperative ileus (POI) is a common complication of radical cystectomy (RC), occurring in 1.6-23.5% of cases. It is defined heterogeneously in the literature. POI increases hospital length of stay and postoperative morbidity. Factors such as age, epidural use, length of procedure, and blood loss may impact POI. In this study, we aimed to evaluate risk factors that contribute to POI in a cohort of patients managed with a comprehensive Enhanced Recovery After Surgery (ERAS) protocol. METHODS: A retrospective review of consecutive patients who underwent RC from March 2015 to December 2016 at Vancouver General Hospital was performed. POI was defined a priori as insertion of nasogastric tube for nausea or vomiting, or failure to advance to a solid diet by the seventh postoperative day. To illustrate heterogeneity in previous studies, we also evaluated POI using other previously reported definitions in the RC literature. The influence of potential risk factors for POI, including patient comorbidities, American Society of Anesthesiologists score, gender, age, prior abdominal surgery or radiation, length of operation, diversion type, extent of lymph node dissection, removal date of analgesic catheter, blood loss, and fluid administration volume was analyzed. RESULTS: Thirty-six (27%) of 136 patients developed POI. Using other previously reported definitions for POI, the incidence ranged from <1-51%. Node-positive status and age at surgery were associated with POI on univariate analysis but not multivariable analysis. CONCLUSIONS: A large range of POI incidence was observed using previously published definitions of POI. We advocate for a standardized definition of POI when evaluating RC outcomes. POI occurs frequently even with a comprehensive ERAS protocol, suggesting that additional measures are needed to reduce the rate of POI.
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INTRODUCTION: Prostate incidentalomas are prostatic lesions suspicious for cancer discovered by imaging patients without a known history of prostatic cancer (PCa) for other reasons. 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET) is used to diagnose, stage, and assess response to treatment for numerous cancers, but it is not routinely used for PCa. We aimed to determine the rate of detection of prostate incidentalomas in patients undergoing FDG PET and to evaluate the natural history of these lesions. METHODS: A retrospective review was conducted of all FDG PET scans performed between 2005 and 2017 at a single institution. Patients were selected who had prostatic uptake without a history of PCa. Clinical data were collected from electronic medical records to determine how the prostate incidentalomas were further evaluated and to define the rate of malignancy. RESULTS: A prostate incidentaloma was identified in 309 (1.0%) of 31 019 FDG PET scans performed on men. A prostate-specific antigen (PSA) test was obtained in 40.1% of patients within six months of prostate incidentaloma detection. Six patients underwent a multiparametric magnetic resonance imaging (mpMRI) of the prostate, which identified PCa in one case. Overall, PCa was diagnosed in 33 cases, representing 10.7% of the prostate incidentalomas and 0.1% of the scanned patients. PCa was intermediate- or high-risk in 27 (8.7%) of the prostate incidentalomas. CONCLUSIONS: Incidental lesions detected in the prostate by FDG PET may represent clinically significant PCa. Referral to a urologist for further evaluation should be considered if the patient is otherwise in reasonable health.
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INTRODUCTION: Radical cystectomy (RC) is a challenging procedure with significant morbidity, though remains the standard of care treatment for many patients with bladder cancer. There has been debate regarding the utility of universal risk calculators to aid in point-of-care prediction of complications in individual patients preoperatively. We retrospectively evaluated the predictive value of the ACS NSQIP universal surgical risk calculator in our patients who underwent RC. METHODS: A prospective cohort of patients undergoing RC was retrospectively reviewed between October 2014 and August 2017. Only patients who underwent a RC for genitourinary cancer without significant deviation from NSQIP surgery codes 51590, 51595, and 51596 (n = 29) were included. The accuracy of the risk calculator was assessed by ROC AUC and Brier scores for both NSQIP and Clavien-Dindo defined complications. Additionally, each NSQIP risk factor was individually assessed for association with postoperative complications. RESULTS: 223 patients who underwent open or robotic RC (n = 18) were included for analysis. Determined by AUC C-stat and Brier scores, prediction was good for cardiac complications (0.80 and 0.021), fair for pneumonia (0.75 and 0.017), poor for UTI (0.64 and 0.078), 30-day mortality (0.62 and 0.013), any complication (0.60 and 0.19) and serious complication (0.60 and 0.17). There was a significant discordance between the rate of NSQIP predicted vs. Clavien-Dindo observed any and serious complications: 28.8% vs. 67.3%, and 25.3% vs. 11.7%, respectively. CONCLUSION: The NSQIP universal surgical risk calculator did not perform with enough accuracy to consider adoption into clinical practice.
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Cistectomia/normas , Complicações Pós-Operatórias/epidemiologia , Melhoria de Qualidade , Medição de Risco , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cistectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco/normasRESUMO
PURPOSE OF REVIEW: As our molecular understanding of bladder cancer continues to advance, more and more novel agents are entering clinical trials across the spectrum of bladder cancer stages. The clinical trial activity for non-muscle invasive bladder cancer (NMIBC) has been boosted further by the evolution of specific disease states that set more uniform inclusion criteria for clinical trial design. Here, we aimed to review the current clinical trials landscape in non-muscle invasive bladder cancer with respect to these disease states. RECENT FINDINGS: Most active clinical trials focus on high-risk NMIBC in either the BCG-naïve or BCG-unresponsive setting. Strict criteria to define the disease state and a clear pathway to drug registration have encouraged trials for patients with BCG-unresponsive NMIBC. The most promising potential breakthroughs for BCG-naïve patients include alternative BCG strains, immune-priming with intradermal BCG vaccination, and systemic immune checkpoint blockade. The latter therapy is also being actively investigated in multiple trials in BCG-unresponsive NMIBC, along with novel viral agents such as INSTILADRIN (nadofaragene firadenovec) and targeted agents such as oportuzumab monatox. After many years of relative stagnation, multiple new therapies currently under investigation in well-designed clinical trials appear poised for routine clinical implementation in the near future. These therapies should dramatically improve the outcome of patients with NMIBC. We can look forward to the challenges of biomarker-driven drug selection, optimal drug sequencing, and rational combination therapies.
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Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Aziridinas/uso terapêutico , Carcinoma de Células de Transição/patologia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Indolquinonas/uso terapêutico , Injeções Intradérmicas , Mitomicina/uso terapêutico , Músculo Liso/patologia , Invasividade Neoplásica , Polissacarídeos Bacterianos/uso terapêutico , Proteínas/uso terapêutico , Proteínas Recombinantes de Fusão , Tamoxifeno/uso terapêutico , Vacinas Tíficas-Paratíficas/uso terapêutico , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos UrológicosRESUMO
PURPOSE OF REVIEW: A bladder-preserving approach for high-grade nonmuscle invasive bladder cancer that has invaded the lamina propria (T1HG) may result in increased recurrence, progression, and even death from bladder cancer in some patients. Initial radical cystectomy does have increased cancer-specific survival (CSS), but represents significant overtreatment for many patients. An evidence-based, risk-stratified approach is required to select patients for immediate radical cystectomy in order to improve CSS. RECENT FINDINGS: A restaging transurethral resection aids in optimal staging and treatment of T1HG. Intravesical Bacillus Calmette-Guerin induction followed by 3 years of maintenance is the standard adjuvant management. However, when very high-risk (hydronephrosis, abnormal bimanual examination, variant histology, lymphovascular invasion, or residual disease on re-resection, and Bacillus Calmette-Guerin failure or early recurrence) or multiple high-risk factors (concomitant CIS, size >3âcm, multifocality, unfavorable tumor location, extensive lamina propria invasion, and elderly) are present, the risk of progression often outweighs the risk associated with radical cystectomy. In these cases, an immediate radical cystectomy likely provides an improved opportunity for cure compared to a bladder-preserving strategy. SUMMARY: In order to increase the CSS of patients diagnosed with T1HG bladder cancer, an aggressive approach may benefit those with increased risk of progression.
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Medicina Baseada em Evidências/métodos , Recidiva Local de Neoplasia/terapia , Seleção de Pacientes , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Vacina BCG/uso terapêutico , Cistectomia/métodos , Progressão da Doença , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão/métodos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Noninfectious penile lesions are classified by clinical presentation as papulosquamous (e.g., psoriasis), inflammatory (e.g., lichen sclerosus, lichen nitidus, lichen planus), vascular (e.g., angiokeratomas), or neoplastic (e.g., carcinoma in situ, invasive squamous cell carcinoma). Psoriasis presents as red or salmon-colored plaques with overlying silvery scales, often with extragenital cutaneous lesions. Lichen sclerosus presents as a phimotic, hypopigmented prepuce or glans penis with a cellophane-like texture. Lichen nitidus usually produces asymptomatic pinhead-sized, hypopigmented papules. The lesions of lichen planus are pruritic, violaceous, polygonal papules that are typically systemic. Angiokeratomas are typically asymptomatic, well-circumscribed, red or blue papules, often with annular or figurate configurations. Carcinoma in situ should be suspected if there are velvety red or keratotic plaques on the glans penis or prepuce, whereas invasive squamous cell carcinoma presents as a painless lump, ulcer, or fungating mass. Some benign lesions, such as psoriasis and lichen planus, may mimic carcinoma in situ or invasive squamous cell carcinoma. Biopsy is indicated if the diagnosis is in doubt or neoplasm cannot be excluded. The management of benign noninfectious penile lesions usually involves observation, topical corticosteroids, or topical calcineurin inhibitors. Neoplastic lesions generally warrant organ-sparing surgery.