RESUMO
BACKGROUND: The first-in-class hypoxia-inducible factor-2α inhibitor, belzutifan, showed clinically meaningful antitumour activity in von Hippel-Lindau (VHL) disease-associated neoplasms in the ongoing, single-arm, phase 2 LITESPARK-004 study. We aimed to investigate antitumour activity with an additional 16 months of follow-up and present updated results for the subgroup of patients with CNS haemangioblastomas. METHODS: In the multicentre, single-arm, phase 2 LITESPARK-004 study, adults (aged ≥18 years) from 11 cancer centres or hospitals in the USA, Denmark, France, and the UK, with germline VHL alterations, at least one measurable renal cell carcinoma tumour, no renal cell carcinoma tumour greater than 3 cm requiring immediate surgical intervention, an Eastern Cooperative Oncology Group performance status 0 or 1, and no previous systemic therapy received oral belzutifan 120 mg once daily until unacceptable toxicity, disease progression, or patient decision to withdraw. The primary endpoint, evaluated in patients with CNS haemangioblastomas, was the proportion of patients with an objective response per RECIST version 1.1 by an independent review committee. We assessed response using two approaches. In approach 1, we evaluated all measurable (≥1 cm maximum diameter) or non-measurable lesions at baseline, including both the solid lesion and the associated cystic component if present. In approach 2, we evaluated only baseline lesions with a measurable (≥1 cm maximum diameter) solid lesion. Antitumour activity was assessed in all patients who received at least one dose of belzutifan. This study is no longer recruiting but is ongoing, and is registered with Clinicaltrials.gov, NCT03401788. FINDINGS: Between May 31, 2018, and March 29, 2019, of 67 patients screened, 61 (32 [52%] male and 29 [48%] female) were enrolled; 50 (82%) had at least one CNS haemangioblastoma evaluable at baseline (184 total lesions). Median follow-up for the 50 patients with CNS haemangioblastomas was 38·0 months (IQR 36·7-40·1). In approach 1, 22 of 50 patients (44% [95% CI 30-59]) had an objective response. In approach 2, 19 of 25 patients (76% [55-91] had an objective response. 23 (46%) of 50 patients had a grade 3-5 all-cause adverse event. 19 (38%) patients reported grade 3 adverse events, the most common of which was anaemia (in 6 [12%] patients). Two of 50 patients (4%) reported grade 4 events (retinal vein occlusion and embolism). Two patients died owing to adverse events not considered treatment-related (suicide and toxicity to various agents). INTERPRETATION: Belzutifan showed meaningful antitumour activity in VHL disease-associated CNS haemangioblastomas that was sustained for more than 3 years of treatment. These results continue to support belzutifan as a systemic treatment option for patients with VHL disease-related CNS haemangioblastomas. FUNDING: Merck Sharp & Dohme, National Institutes of Health, and National Cancer Institute.
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Hemangioblastoma , Doença de von Hippel-Lindau , Humanos , Masculino , Feminino , Hemangioblastoma/tratamento farmacológico , Hemangioblastoma/patologia , Pessoa de Meia-Idade , Adulto , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/patologia , Idoso , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto JovemRESUMO
PURPOSE: To report the efficacy of the oral hypoxia-inducible factor 2α inhibitor belzutifan in participants with von Hippel-Lindau disease-associated retinal hemangioblastomas in the LITESPARK-004 study. DESIGN: Subgroup analysis of the phase 2, single-arm, open-label LITESPARK-004 study. PARTICIPANTS: Adults with 1 or more von Hippel-Lindau disease-associated measurable renal cell carcinoma tumors not requiring immediate surgical intervention were eligible. METHODS: Participants received oral belzutifan 120 mg once daily until disease progression or unacceptable treatment-related toxicity. MAIN OUTCOME MEASURES: Efficacy of belzutifan in retinal hemangioblastomas was a secondary end point, measured as response (improved, stable, or progressed) by independent reading center-certified graders based on color fundus imaging performed every 12 weeks using the investigator's preferred imaging standards. Additional assessments, where available, included OCT and ultra-widefield fluorescein angiography. RESULTS: Among 61 participants in LITESPARK-004, 12 had 1 or more evaluable active retinal hemangioblastomas in 16 eyes at baseline per independent reading center. As of April 1, 2022, the median follow-up for participants with ocular von Hippel-Lindau disease at baseline was 37.3 months. All 16 eyes were graded as improved, with a response rate of 100.0% (95% confidence interval, 79.4%-100%). No new retinal hemangioblastomas or ocular disease progression were reported as of data cutoff date. Eight participants underwent additional multimodal eye assessments performed at the National Institutes of Health study site. Among this subgroup, 10 of 24 hemangioblastomas in 8 eyes of 6 participants measured 500 µm or more in greatest linear dimension at baseline and were analyzed further. All 10 hemangioblastomas had a mean area reduction of 15% or more by month 12 and of 30% or more by month 24. CONCLUSIONS: Belzutifan showed promising activity against ocular von Hippel-Lindau disease, including capacity to control retinal hemangioblastomas, with effects sustained for more than 2 years while treatment is ongoing. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Angiofluoresceinografia , Hemangioblastoma , Neoplasias da Retina , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/tratamento farmacológico , Feminino , Masculino , Hemangioblastoma/tratamento farmacológico , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/diagnóstico , Pessoa de Meia-Idade , Adulto , Administração Oral , Idoso , Acuidade Visual/fisiologia , Tomografia de Coerência Óptica , Adulto Jovem , Resultado do Tratamento , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
PURPOSE: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas]. PATIENTS AND METHODS: Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety. RESULTS: All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1-46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was -4.2 mm per year (range, -7.9 to -0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred. CONCLUSIONS: Belzutifan continued to show robust activity and manageable safety in VHL disease-associated pNETs.
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Neoplasias Pancreáticas , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/tratamento farmacológico , Doença de von Hippel-Lindau/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Idoso , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Adulto Jovem , Resultado do Tratamento , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Cistadenoma Seroso/tratamento farmacológico , Cistadenoma Seroso/patologiaRESUMO
Prostate cancer has a wide spectrum ranging between low-grade localized disease and castrate-resistant metastatic disease. Although whole gland and systematic therapies result in cure in the majority of patients, recurrent and metastatic prostate cancer can still occur. Imaging approaches including anatomic, functional, and molecular modalities are continuously expanding. Currently, recurrent and metastatic prostate cancer is grouped in three major categories: 1) Clinical concern for residual or recurrent disease after radical prostatectomy, 2) Clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments, and 3) Metastatic prostate cancer treated by systemic therapy (androgen deprivation therapy, chemotherapy, immunotherapy). This document is a review of the current literature regarding imaging in these settings and the resulting recommendations for imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Estados Unidos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Antagonistas de Androgênios , Seguimentos , Diagnóstico por Imagem/métodos , Sociedades MédicasRESUMO
The staging and surveillance of testicular cancer is a complex topic, which integrates clinical, biochemical, and imaging components. The use of imaging for staging and surveillance of testicular cancer is individually tailored to each patient by considering tumor histology and prognosis. This document discusses the rationale for use of imaging by imaging modality during the initial staging of testicular seminoma and nonseminoma tumors and during the planned surveillance of stage IA and IB testicular cancer by histological subtype integrating clinical suspicion for disease recurrence in surveillance protocols. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Neoplasias Testiculares , Diagnóstico por Imagem , Medicina Baseada em Evidências , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas , Sociedades Médicas , Neoplasias Testiculares/diagnóstico por imagem , Estados UnidosRESUMO
BACKGROUND: Patients with von Hippel-Lindau (VHL) disease have a high incidence of renal cell carcinoma owing to VHL gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α). METHODS: In this phase 2, open-label, single-group trial, we investigated the efficacy and safety of the HIF-2α inhibitor belzutifan (MK-6482, previously called PT2977), administered orally at a dose of 120 mg daily, in patients with renal cell carcinoma associated with VHL disease. The primary end point was objective response (complete or partial response) as measured according to the Response Evaluation Criteria in Solid Tumors, version 1.1, by an independent central radiology review committee. We also assessed responses to belzutifan in patients with non-renal cell carcinoma neoplasms and the safety of belzutifan. RESULTS: After a median follow-up of 21.8 months (range, 20.2 to 30.1), the percentage of patients with renal cell carcinoma who had an objective response was 49% (95% confidence interval, 36 to 62). Responses were also observed in patients with pancreatic lesions (47 of 61 patients [77%]) and central nervous system hemangioblastomas (15 of 50 patients [30%]). Among the 16 eyes that could be evaluated in 12 patients with retinal hemangioblastomas at baseline, all (100%) were graded as showing improvement. The most common adverse events were anemia (in 90% of the patients) and fatigue (in 66%). Seven patients discontinued treatment: four patients voluntarily discontinued, one discontinued owing to a treatment-related adverse event (grade 1 dizziness), one discontinued because of disease progression as assessed by the investigator, and one patient died (of acute toxic effects of fentanyl). CONCLUSIONS: Belzutifan was associated with predominantly grade 1 and 2 adverse events and showed activity in patients with renal cell carcinomas and non-renal cell carcinoma neoplasms associated with VHL disease. (Funded by Merck Sharp and Dohme and others; MK-6482-004 ClinicalTrials.gov number, NCT03401788.).
Assuntos
Antineoplásicos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Carcinoma de Células Renais/tratamento farmacológico , Indenos/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Doença de von Hippel-Lindau/complicações , Adulto , Idade de Início , Idoso , Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/etiologia , Progressão da Doença , Fadiga/induzido quimicamente , Feminino , Seguimentos , Hemangioblastoma/tratamento farmacológico , Humanos , Indenos/efeitos adversos , Neoplasias Renais/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Doença de von Hippel-Lindau/genéticaRESUMO
The diagnosis, evaluation and management of patients with renal cell carcinoma has transformed in the 21st century. Utilizing biological discoveries and technological advances, the field has moved from blunt surgical and largely ineffective medical treatments, to nuanced and fine-tuned approaches based on biology, extent of disease and patient preferences. In this review we will summarize the last 25 years of progress in kidney cancer.
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Pesquisa Biomédica , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/terapia , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Pesquisa Biomédica/história , Pesquisa Biomédica/tendências , Carcinoma de Células de Transição/história , História do Século XX , História do Século XXI , Humanos , Neoplasias Renais/história , Fatores de TempoRESUMO
Urothelial cancer is the second most common cancer, and cause of cancer death, related to the genitourinary tract. The goals of surveillance imaging after the treatment of urothelial cancer of the urinary bladder are to detect new or previously undetected urothelial tumors, to identify metastatic disease, and to evaluate for complications of therapy. For surveillance, patients can be stratified into one of three groups: 1) nonmuscle invasive bladder cancer with no symptoms or additional risk factors; 2) nonmuscle invasive bladder cancer with symptoms or additional risk factors; and 3) muscle invasive bladder cancer. This document is a review of the current literature for urothelial cancer and resulting recommendations for surveillance imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Carcinoma de Células de Transição , Radiologia , Neoplasias da Bexiga Urinária , Medicina Baseada em Evidências , Humanos , Sociedades Médicas , Estados Unidos , Neoplasias da Bexiga Urinária/diagnóstico por imagemRESUMO
Urinary tract infections (UTIs) in women are common, with an overall lifetime risk over >50%. UTIs are considered recurrent when they follow complete clinical resolution of a previous UTI and are usually defined as at least three episodes of infection within the preceding 12 months. An uncomplicated UTI is classified as a UTI without structural or functional abnormalities of the urinary tract and without relevant comorbidities. Complicated UTIs are those occurring in patients with underlying structural or medical problems. In women with recurrent uncomplicated UTIs, cystoscopy and imaging are not routinely used. In women suspected of having a recurrent complicated UTI, cystoscopy and imaging should be considered. CT urography or MR urography are usually appropriate for the evaluation of recurrent complicated lower urinary tract infections or for women who are nonresponders to conventional therapy, develop frequent reinfections or relapses, or have known underlying risk factors. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Sociedades Médicas , Infecções Urinárias , Medicina Baseada em Evidências , Feminino , Humanos , Imageamento por Ressonância Magnética , Estados Unidos , Infecções Urinárias/diagnóstico por imagemRESUMO
INTRODUCTION: Intraoperative surgical outcomes are influenced by a wide variety of patient, surgeon and institutional factors. The current literature lacks comprehensive resources that describe best practices in preventing patient safety events and optimizing patient physiology during urological surgery. METHODS: A multidisciplinary panel of subject matter experts (urologists, nurses, anesthesiologists) was convened to evaluate the existing literature, create a white paper and disseminate this to urological providers. Focusing on intraoperative patient safety and physiology, a narrative review was undertaken and relevant guidelines and practical interventions were highlighted. RESULTS: Patient safety is optimized by preventing surgical site infections, wrong site surgery, venous thromboembolism, falls/positioning injuries, laser/fire injuries, excessive radiation exposure and harm from the adoption of new technology. Goals for intraoperative physiological parameters (temperature, glucose, fluid balance) are addressed as well as analgesic and anesthetic considerations in urological patients. In addition, practical tools are provided to assist in the quality improvement process. CONCLUSIONS: This article summarizes intraoperative factors related to patient safety and optimal physiology that can impact urological surgical outcomes. This overview can be used as a practical guide for process improvement to optimize the quality of intraoperative care.
RESUMO
Lower urinary tract symptoms due to benign prostatic enlargement have a high prevalence in men over 50 years of age. Diagnosis is made with a combination of focused history and physician examination and validated symptom questionnaires. Urodynamic studies can help to differentiate storage from voiding abnormalities. Pelvic ultrasound may be indicated to assess bladder volume and wall thickness. Other imaging modalities, including prostate MRI, are usually not indicated in the initial workup and evaluation of uncomplicated lower urinary tract symptoms from an enlarged prostate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Sintomas do Trato Urinário Inferior/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico por imagem , Radiologia/normas , Urodinâmica/fisiologia , Idoso , Medicina Baseada em Evidências , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Controle de Qualidade , Sociedades Médicas/normas , Ultrassonografia Doppler/métodos , Estados UnidosRESUMO
Lower urinary tract injury is most commonly the result of blunt trauma but can also result from penetrating or iatrogenic trauma. Clinical findings in patients with a mechanism of penetrating trauma to the lower urinary tract include lacerations or puncture wounds of the pelvis, perineum, buttocks, or genitalia, as well as gross hematuria or inability to void. CT cystography or fluoroscopy retrograde cystography are usually the most appropriate initial imaging procedures in patients with a mechanism of penetrating trauma to the lower urinary tract. CT of the pelvis with intravenous contrast, pelvic radiography, fluoroscopic retrograde urethrography, and CT of the pelvis without intravenous contrast may be appropriate in some cases. Arteriography, radiographic intravenous urography, CT of the pelvis without and with intravenous contrast, ultrasound, MRI, and nuclear scintigraphy are usually not appropriate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Guias de Prática Clínica como Assunto , Bexiga Urinária/lesões , Sistema Urinário/lesões , Ferimentos Penetrantes/diagnóstico por imagem , Traumatismos Abdominais/cirurgia , Meios de Contraste , Cistografia/métodos , Medicina Baseada em Evidências , Feminino , Humanos , Escala de Gravidade do Ferimento , Imageamento por Ressonância Magnética/métodos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Controle de Qualidade , Radiologia/normas , Sensibilidade e Especificidade , Sociedades Médicas/normas , Tomografia Computadorizada por Raios X/métodos , Estados Unidos , Uretra/diagnóstico por imagem , Uretra/lesões , Bexiga Urinária/diagnóstico por imagem , Sistema Urinário/diagnóstico por imagemRESUMO
Urothelial cancer is the second most common cancer, and cause of cancer death, related to the genitourinary tract. The goals of surveillance imaging after the treatment of urothelial cancer of the urinary bladder are to detect new or previously undetected urothelial tumors, to identify metastatic disease, and to evaluate for complications of therapy. For surveillance, patients can be stratified into one of three groups: (1) nonmuscle invasive bladder cancer with no symptoms or additional risk factors; (2) nonmuscle invasive bladder cancer with symptoms or additional risk factors; and (3) muscle invasive bladder cancer. This article is a review of the current literature for urothelial cancer and resulting recommendations for surveillance imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Carcinoma de Células de Transição/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Guias de Prática Clínica como Assunto , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Cistografia/métodos , Cistoscopia/métodos , Medicina Baseada em Evidências , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Monitorização Fisiológica , Gradação de Tumores , Invasividade Neoplásica/patologia , Prognóstico , Controle de Qualidade , Radiologia/normas , Sensibilidade e Especificidade , Sociedades Médicas/normas , Tomografia Computadorizada por Raios X/métodos , Estados Unidos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: We previously reported the presence of prostate-specific antigen (PSA) in the stromal compartment of benign prostatic hyperplasia (BPH). Since PSA is expressed exclusively by prostatic luminal epithelial cells, PSA in the BPH stroma suggests increased tissue permeability and the compromise of epithelial barrier integrity. E-cadherin, an important adherens junction component and tight junction regulator, is known to exhibit downregulation in BPH. These observations suggest that the prostate epithelial barrier is disrupted in BPH and E-cadherin downregulation may increase epithelial barrier permeability. METHODS: The ultra-structure of cellular junctions in BPH specimens was observed using transmission electron microscopy (TEM) and E-cadherin immunostaining analysis was performed on BPH and normal adjacent specimens from BPH patients. In vitro cell line studies using benign prostatic epithelial cell lines were performed to determine the impact of small interfering RNA knockdown of E-cadherin on transepithelial electrical resistance and diffusion of fluorescein isothiocyanate (FITC)-dextran in transwell assays. RESULTS: The number of kiss points in tight junctions was reduced in BPH epithelial cells as compared with the normal adjacent prostate. Immunostaining confirmed E-cadherin downregulation and revealed a discontinuous E-cadherin staining pattern in BPH specimens. E-cadherin knockdown increased monolayer permeability and disrupted tight junction formation without affecting cell density. CONCLUSIONS: Our results indicate that tight junctions are compromised in BPH and loss of E-cadherin is potentially an important underlying mechanism, suggesting targeting E-cadherin loss could be a potential approach to prevent or treat BPH.
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Caderinas/metabolismo , Regulação para Baixo , Células Epiteliais/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Junções Íntimas/metabolismo , Caderinas/genética , Humanos , Masculino , PermeabilidadeRESUMO
An acute scrotum is defined as testicular swelling with acute pain and can reflect multiple etiologies including epididymitis or epididymo-orchitis, torsion of the spermatic cord, or torsion of the testicular appendages. Quick and accurate diagnosis of acute scrotum and its etiology with imaging is necessary because a delayed diagnosis of torsion for as little as 6 hours can cause irreparable testicular damage. Ultrasound duplex Doppler of the scrotum is usually appropriate as the initial imaging for the acute onset of scrotal pain without trauma or antecedent mass in an adult or child. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Dor Aguda/diagnóstico por imagem , Escroto/diagnóstico por imagem , Doenças Testiculares/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos , Masculino , Sociedades Médicas , Estados UnidosRESUMO
ABSTRACT Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.
Assuntos
Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Bexiga Urinária/radioterapia , Irradiação Craniana/métodos , Carcinoma de Células Pequenas/radioterapia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Análise de Sobrevida , Estudos Retrospectivos , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapiaRESUMO
PURPOSE: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. MATERIALS AND METHODS: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. RESULTS: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. CONCLUSION: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.
Assuntos
Carcinoma de Células Pequenas/radioterapia , Irradiação Craniana , Neoplasias da Bexiga Urinária/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Irradiação Craniana/métodos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Análise de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Muscle-invasive bladder cancer (MIBC) has a tendency toward urothelial multifocality and is at risk for local and distant spread, most commonly to the lymph nodes, bone, lung, liver, and peritoneum. Pretreatment staging of MIBC should include imaging of the urothelial upper tract for synchronous lesions; imaging of the chest, abdomen, and pelvis for metastases; and MRI pelvis for local staging. CT abdomen and pelvis without and with contrast (CT urogram) is recommended to assess the urothelium and abdominopelvic organs. Pelvic MRI can improve local bladder staging accuracy. Chest imaging is also recommended with chest radiograph usually being adequate. FDG-PET/CT may be appropriate to identify nodal and metastatic disease. Chest CT may be useful in high-risk patients and those with findings on chest radiograph. Nonurogram CT and MRI of the abdomen and pelvis are usually not appropriate, and neither is radiographic intravenous urography, Tc-99m whole body bone scan, nor bladder ultrasound for pretreatment staging of MIBC. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Meios de Contraste , Medicina Baseada em Evidências , Humanos , Estadiamento de Neoplasias , Sociedades Médicas , Estados UnidosRESUMO
INTRODUCTION: Multimodal analgesia is an effective way to control pain and limit opioid use after surgery. The quadratus lumborum block and paravertebral block are two regional anesthesia techniques that leverage multimodal analgesia to improve postoperative pain control. We sought to compare the efficacy of these blocks for pain management following radical cystectomy. MATERIALS AND METHODS: We performed a retrospective review of radical cystectomy patients who received bilateral continuous paravertebral blocks (n = 125) or bilateral single shot quadratus lumborum blocks (n = 50) between 2014-2016. The primary outcome was postoperative opiate consumption on day 0. Secondary outcomes included self-reported pain scores and hospital length of stay. RESULTS: Quadratus lumborum block patients had similar opioid use on postoperative day 0 compared with paravertebral block patients (29 mg versus 30 mg, p = 0.90). Pain scores on postoperative day 0 were similar between quadratus lumborum block and paravertebral block groups (4.0 versus 3.8, p = 0.72); however, the paravertebral block group had lower pain scores on days 1-3 compared with the quadratus lumborum block group (all p < 0.05). Hospital length of stay was similar between groups (6.6 days versus 6.2 days, p = 0.41). CONCLUSIONS: There were no differences in opioid consumption among patients receiving bilateral single shot quadratus lumborum blocks and bilateral continuous paravertebral blocks after radical cystectomy. These data suggest that the quadratus lumborum block is a viable alternative for delivering multimodal analgesia in cystectomy patients.