RESUMO
PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. METHODS: The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. RESULTS: Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent. CONCLUSION: Intraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP. REGISTRATION: ISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036 .
Assuntos
Antígenos de Superfície , Glutamato Carboxipeptidase II , Imagem Óptica , Prostatectomia , Neoplasias da Próstata , Masculino , Humanos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Glutamato Carboxipeptidase II/metabolismo , Antígenos de Superfície/metabolismo , Imagem Óptica/métodos , Período Intraoperatório , Pessoa de Meia-Idade , Animais , Idoso , Cirurgia Assistida por Computador/métodos , CamundongosRESUMO
OBJECTIVES: Primary objectives: to determine whether local anaesthetic transperineal prostate (LATP) biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e., any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: to compare (i) infection rates, (ii) health-related quality of life, (iii) patient-reported procedure tolerability, (iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), (v) number of subsequent prostate biopsy procedures required, (vi) cost-effectiveness, (vii) other histological parameters, and (viii) burden and rate of detection of clinically insignificant PCa (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multicentre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in six sectors (depending on prostate size), plus three to five target cores per multiparametric/bi-parametric magnetic resonance imaging lesion. LATP biopsy is performed using an ultrasound probe-mounted needle-guidance device (either the 'Precision-Point' or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa vs 45% for TRUS biopsy). A total of 1042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy vs TRUS biopsy in the primary diagnostic setting.
Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Estudos Prospectivos , Qualidade de Vida , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Biópsia/efeitos adversos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Prostate cancer is the tumor with the highest incidence among men and one of Chile's leading causes of death. AIM: To analyze temporal trends in prostate cancer mortality in Chile. MATERIAL AND METHODS: Mortality rates in Chile for the period between 1955 and 2019 were calculated. The number of deaths was obtained from the national demographic yearbooks and the Ministery of Health mortality registries. Population estimates from the demographic center of the Economic Commission for Latin America and the Caribbean of the United Nations were used. Chilean census population of 2017 was used as reference to calculate adjusted rates. Trends were analyzed using a join point regression. RESULTS: Crude mortality rates of prostatic cancer increased between 1995 and 2012 in three different phases, namely between 1955 and 1989 with a 2.7% annual increase, between 1989 and 1996 at a 6.8% annual rate, and between 1996 to 2012 with a 2.8% annual increase. From 2012 the rate remained stable. Adjusted mortality rates increased slowly at a 1.7% rate from 1955 to 1993, accelerating between 1993 and 1996, when they increased 12.1% per year. From 1996 onwards there was a significant decrease in mortality at a 1.2% annual rate. This decrease was significant and observed within all age groups but more importantly at older ages. CONCLUSIONS: Prostate cancer mortality in Chile has decreased significantly during the last two decades, like that observed in developed nations.
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Neoplasias da Próstata , Masculino , Humanos , Chile/epidemiologia , América Latina , Incidência , MortalidadeRESUMO
OBJECTIVES: To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability. PATIENTS AND METHODS: Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs). RESULTS: Some 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either 'not at all' or 'a little' painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re-biopsy, 48% said it would be 'not a problem' and in contrast 8.1% would consider it a 'major problem'. Most of the patients (81%) described the biopsy as a 'minor or moderate procedure tolerable under local anaesthesia', while 5.6% perceived it as a 'major procedure that requires general anaesthesia'. CONCLUSION: Our data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound-guided biopsy (TRUS) to investigate the relative trade-offs between each biopsy technique would be helpful.
Assuntos
Anestesia Local , Próstata/patologia , Idoso , Biópsia/instrumentação , Biópsia/métodos , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Períneo , Estudos ProspectivosRESUMO
Robot-assisted radical prostatectomy has become the standard of care for the removal of localized prostate cancer. Positive outcomes depend upon the precise removal of the prostate and associated tissue without damage to nearby structures. This process can be aided by fluorescence-guided surgery to enhance the visual contrast between different structures. Here the authors have conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify ten investigations into the use of fluorescence-guided surgery in robot-assisted radical prostatectomy. These studies used fluorescent tracers to identify structures, including the prostate, neurovascular bundle and lymph nodes. These studies demonstrate the safe and effective use of fluorescence-guided surgery in robot-assisted radical prostatectomy and pave the way for further developments in this field.
Assuntos
Corantes Fluorescentes/uso terapêutico , Prostatectomia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Fluorescência , Corantes Fluorescentes/metabolismo , Humanos , Período Intraoperatório , Linfonodos/metabolismo , Linfonodos/cirurgia , Masculino , Tratamentos com Preservação do Órgão , Próstata/inervação , Próstata/metabolismo , Próstata/cirurgiaRESUMO
PURPOSE: In this study we assessed bladder cancer health care and mortality trends in recent decades in a well studied arsenic exposed area in Northern Chile. MATERIALS AND METHODS: Arsenic levels in the affected region were obtained for the last 60 years, and correlated with bladder cancer hospital discharge and mortality rates in recent decades. RESULTS: Bladder cancer hospital discharge rates were significantly higher in the affected region (peak RR 3.6, 95% CI 3.0-4.7). Mortality rates for bladder cancer showed a trend of increase during the period analyzed, reaching peak mortality rates of 28.4 per 100,000 for men and 18.7 per 100,000 for women in the last 10 years. Poisson regression models showed an increased mortality risk in the studied region compared to the rest of the country until the present for men (IRR 5.3, 95% CI 4.8-5.8) and women (IRR 7.8, 95% CI 7.0-8.7). Mean age at cancer specific death was significantly lower in the exposed region (69.6 years, 95% CI 68.4-70.7 vs 73.7 years, 95% CI 73.3-74.2, p <0.01). CONCLUSIONS: Exposure to arsenic is related to a significant need for bladder cancer health care and to high mortality rates even 20 years after having controlled arsenic levels in drinking water. Affected individuals should be aware of the significant impact of this ecological factor. Further research is required to identify strategies for the management of bladder cancer in arsenic exposed populations.
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Intoxicação por Arsênico/complicações , Arsênio/análise , Neoplasias da Bexiga Urinária/induzido quimicamente , Abastecimento de Água/análise , Idoso , Intoxicação por Arsênico/mortalidade , Chile/epidemiologia , Feminino , Humanos , Incidência , Masculino , Distribuição de Poisson , Fatores de Tempo , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
An experimental study in pigs was designed to evaluate the consequences of normothermic ischemia in hypothermic isolated renal perfusion (HP). We perfused 16 kidneys after 45 minutes of vascular occlusion. Another 16 kidneys were perfused without previous warm ischemia. The ureter was catheterized in all procedures and the output collected during HP. Creatinine was added to the perfusion solution initially in order to determine creatinine clearance (CrCl). HP hydrodynamics were recorded in real time through a computerized system. According to the results, renal vascular resistance as well as CrCl were higher in ischemic kidneys. Both facts, along with minimal differences in the microscopic study, suggested an increased vascular tone of the efferent postglomerular arteriole during HP. HP was proven to be an optimal technique to minimize the histological consequences of ischemia. Microvascular and biochemical changes produced during HP may be essentially related to dynamic causes.
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Hipotermia , Isquemia/fisiopatologia , Rim/fisiopatologia , Circulação Renal/fisiologia , Animais , Técnicas In Vitro , Rim/fisiologia , Modelos Animais , Nefrectomia , Perfusão , Suínos , Porco Miniatura , Resistência VascularRESUMO
BACKGROUND: Prostate cancer is the tumor with the highest incidence among men and one of Chile's leading causes of death. AIM: To analyze temporal trends in prostate cancer mortality in Chile. MATERIAL AND METHODS: Mortality rates in Chile for the period between 1955 and 2019 were calculated. The number of deaths was obtained from the national demographic yearbooks and the Ministery of Health mortality registries. Population estimates from the demographic center of the Economic Commission for Latin America and the Caribbean of the United Nations were used. Chilean census population of 2017 was used as reference to calculate adjusted rates. Trends were analyzed using a join point regression. RESULTS: Crude mortality rates of prostatic cancer increased between 1995 and 2012 in three different phases, namely between 1955 and 1989 with a 2.7% annual increase, between 1989 and 1996 at a 6.8% annual rate, and between 1996 to 2012 with a 2.8% annual increase. From 2012 the rate remained stable. Adjusted mortality rates increased slowly at a 1.7% rate from 1955 to 1993, accelerating between 1993 and 1996, when they increased 12.1% per year. From 1996 onwards there was a significant decrease in mortality at a 1.2% annual rate. This decrease was significant and observed within all age groups but more importantly at older ages. CONCLUSIONS: Prostate cancer mortality in Chile has decreased significantly during the last two decades, like that observed in developed nations.