RESUMO
Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM-AIRO-AISP-ANISC-AURO-Fondazione AIOM-SIAPEC/IAP-SIBioC-SICO-SIF-SIGE-SIGU-SIU-SIURO-UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.
Assuntos
Neoplasias Ovarianas , Neoplasias Pancreáticas , Neoplasias da Próstata , Feminino , Humanos , Itália , Masculino , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Sociedades CientíficasRESUMO
BACKGROUND: In search of novel prognostic biomarkers for clear cell renal carcinoma (ccRCC), we analysed the expression of several proteins related to angiogenesis and hypoxia. METHODS: A monocentric study on 30 consecutive surgical samples from surgically-treated ccRCC patients with a 10-year follow up was performed. The following proteins were analysed by immunohistochemistry: Vascular Endothelial Growth Factor- A (VEGF-A), Platelet-Derived Growth Factor ß Receptor (PDGFRß), VEGF-receptor 1 (Flt1), VEGF-receptor 2 (KDR), Glucose Transporter 1 (GLUT1), Carbonic anhydrase IX (CA-IX) and the hERG1 potassium channel. Data were analysed in conjunction with the clinico-pathological characteristics of the patients and follow up. RESULTS: All the proteins were expressed in the samples, with statistically significant associations of VEGF-A with PDGFRß and Flt1 and hERG1 with CA IX. Notably, hERG1 and CAIX co-immunoprecipitated in primary ccRCC samples and survival analysis showed that the positivity for hERG1 and CA IX had a negative impact on Recurrence Free Survival (RFS) at the univariate analysis. At the multivariate analysis only hERG1 maintained its statistically significant negative impact. CONCLUSIONS: hERG1 expression can be exploited to predict recurrence in surgically-treated ccRCC patients. hERG1 channels form a multiprotein complex with the pH regulator CA IX in primary ccRCC samples their potential use as therapeutic target might be suggested.
Assuntos
Biomarcadores Tumorais/metabolismo , Anidrase Carbônica IX/metabolismo , Carcinoma de Células Renais/cirurgia , Canais de Potássio Éter-A-Go-Go/metabolismo , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia/metabolismo , Idoso , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Itália , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia/métodos , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: The Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) is a measure of health-related quality of life (HRQoL) in advanced hormone-resistant prostate cancer. In this study, we aimed at performing a cross-cultural adaptation and validation of the Italian version of the PROSQOLI. PATIENTS AND METHODS: The original version of the PROSQOLI underwent several turnarounds of translations. A total of 472 patients treated with radical prostatectomy, radiotherapy or medical therapy were enrolled for the validation of the questionnaire. The PROSQOLI was administered together with the SF-12. Reliability indexes were calculated by using Cronbach alpha. To evaluate the validity of the construct, relationships between PROSQOLI and SF12 were assessed. The ANOVA test was used to evaluate the differences between groups of patients who had received different treatments. RESULTS: The reliability coefficient was 0.91. Item-to-total correlation indices were in most cases >0.70. The correlation between the scores of the PROSQOLI and those of the SF-12 questionnaire was high (r=0.8139, p<0.0001). The ANOVA test showed significant differences between groups (p<0.01) based on age, recurrence risk and treatment. CONCLUSIONS: The adaptation process showed that the PROSQOLI Italian version has high reliability and presents both convergent and discriminant validity. This version of the tool can be used to assess HRQoL in Italian men who underwent radical treatment for advanced prostate cancer.
Assuntos
Neoplasias da Próstata/terapia , Qualidade de Vida , Inquéritos e Questionários , Humanos , Itália , Masculino , Reprodutibilidade dos TestesRESUMO
AIM: To assess the role of simple enucleation (SE) for the treatment of highly complex renal tumors. METHODS: Overall, 96 Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification score 10 to 13 renal tumors were treated with SE at our institution. All conventional perioperative variables, surgical, functional and oncological results were gathered in a prospectively maintained database. Survival curves were generated using a Kaplan-Meier method. Univariate analysis assessed the outcome differences. RESULTS: Mean (± 1s.d.) clinical tumor diameter was 4.8 (± 1.6 cm). 70.8% of patients had ≥ cT1b stage. The PADUA score was recorded as 10, 11, 12 and 13 in 57.3%, 29.2%, 11.5%, and 2.1% of tumors respectively. Overall, 76 patients were treated with an open approach and 20 robotically. Mean warm ischemia time (WIT) was 19.2 min, and WIT greater than 25 min occurred in 14.6% of cases. Positive surgical margin (PSM) rate was 3.6% and trifecta was achieved in 64.3% of patients. Postoperative surgical complications occurred in 24% of patients, with 14.6% Clavien-Dindo grade 1-2, 8.3% grade 3, and 1% grade 4. Five-year cancer specific survival (CSS), recurrent free survival (RFS), and overall survival (OS) rates resulted 96.1%, 90.8% and 88.0%, respectively. Overall, 4.2% of patients experienced progressive disease. At follow-up, the mean decrease of eGFR from preoperative value was 13.9 ml/min. This was not significantly correlated with PADUA score (p = 0.69). The surgical approach was neither a predictor of Trifecta outcome, nor of postoperative complications, WIT > 25 min or PSM rate. CONCLUSIONS: SE is an effective treatment for highly-complex renal tumors, with a potential key role to widen the NSS (nephron sparing surgery) indications according to guidelines.
Assuntos
Taxa de Filtração Glomerular , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Néfrons , Tratamentos com Preservação do Órgão/métodos , Robótica , Adulto , Idoso , Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Período Perioperatório , Valor Preditivo dos Testes , Estudos Retrospectivos , Baço/lesões , Esplenectomia , Resultado do TratamentoRESUMO
We report a case of a 30 years old male affected by synchronous bilateral germ cell tumor with a history of unilateral cryptorchidism; the patient underwent surgical treatment followed by adjuvant radiotherapy on paraaortic and iliac lymphnodes. Patients with synchronous tumors usually present with a higher stage disease in contrast to those with unilateral testicular carcinoma, yet the prognosis remains equally favorable.
Assuntos
Criptorquidismo/cirurgia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/cirurgia , Adulto , Terapia Combinada , Criptorquidismo/radioterapia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/radioterapia , Prognóstico , Radioterapia Adjuvante , Neoplasias Testiculares/radioterapia , Resultado do TratamentoRESUMO
AIMS: To evaluate the role of nephron-sparing surgery (NSS) compared to radical nephrectomy (RN) for treating multiple ipsilateral renal tumors. METHODS: We retrospectively reviewed the clinical and pathological data of 960 patients who had surgery for pathologically confirmed RCC between 1986 and 2006. Thirty-four patients were diagnosed as having at least one ipsilateral smaller solid lesion associated with the primary RCC: 22 had RN while 12 had NSS for tumor enucleation. RESULTS: All patients who had NSS had tumors confined within the kidney, as did 82% of patients treated with RN. The sole presence of concomitant accompanying benign histology to the primary RCC was diagnosed in 20% of patients. The mean (median, range) follow-up for patients treated with RN and NSS was 69 (58, 12-214) and 58 (44, 12-151) months. Tumor stage was significantly associated with tumor-specific survival (TSS) in the RN group (p<0.001). None of the patients who had tumor enucleation had positive surgical margins. Two patients recurred locally after NSS, elsewhere in the kidney, resulting in a crude ipsilateral recurrence rate of 17%. The analysis of TSS for patients with multiple ipsilateral tumors with a pT1 primary lesion showed no statistically significant differences between patients who had RN or NSS. Two patients had contralateral recurrence, resulting in a crude rate of 6%. CONCLUSIONS: For patients with multiple ipsilateral renal tumors, 20% of the satellite lesions are benign and 6% develop a contralateral metachronous recurrence. We also observed similar TSS for patients treated with NSS and RN.
Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Nefrectomia/métodos , Idoso , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Prognóstico , Estudos Retrospectivos , Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
A 64-year-old man was treated with brachytherapy for prostate cancer. Prostate-specific antigen (PSA) nadir was achieved at 3 months, while at 24 months PSA increased to 18.7 ng ml(-1). Re-biopsy and imaging revealed locally recurrent prostate carcinoma without metastasis. The patient was treated with salvage radical prostatectomy, and the surgical specimen underwent double-blind evaluation with RX scan and whole-mount histopathology sections. Radiology revealed an area without any seeds in the right base of the prostate, and pathologic assessment demonstrated adenocarcinoma involving the right base of the gland. This case is indicative of tumor relapse occurring for seed migration after good initial positioning.
Assuntos
Braquiterapia/instrumentação , Recidiva Local de Neoplasia/sangue , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Terapia Combinada , Método Duplo-Cego , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/diagnóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Terapia de SalvaçãoRESUMO
OBJECTIVES: To evaluate the incidence of positive surgical margins (and associated risk factors) in patients with localized prostate cancer at high preoperative risk of extracapsular disease treated using a modified anterograde radical retropubic prostatectomy technique. Positive surgical margins are an important risk factor for disease recurrence after radical prostatectomy, particularly in patients with extracapsular disease. PATIENTS AND METHODS: In total, 84 patients with clinically localized prostate cancer and a preoperative prostate-specific antigen (PSA) level > 10 ng/mL and/or a biopsy Gleason score > or = 7 were evaluated. The surgical technique allows easy, wide resection of the posterolateral prostatic pedicles, and good mobilization and exposure of the apex before the urethra transection. Prostatectomy specimens were examined for extracapsular tumour spread and positive surgical margins. Differences in putative risk factors (Gleason score, preoperative PSA level, prostate weight) between the positive- and negative-margin groups were evaluated using the Mann-Whitney test. RESULTS: Overall, 11 of the 84 (13%) patients had positive surgical margins and of these a single site was involved in six. In total, 15 positive-margin sites were identified (five apical, four basal, three posterolateral, two anterior and one posterior). All patients with positive margins had histological extracapsular disease. The preoperative PSA level and Gleason score were significantly higher in the positive- than in the negative-margin group (P = 0.025 and 0.035, respectively). CONCLUSIONS: The anterograde radical prostatectomy minimizes the incidence of positive surgical margins in patients at high risk of extracapsular disease.
Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Fatores de RiscoRESUMO
INTRODUCTION: Radical nephrectomy is the treatment of first choice for unilateral renal cell carcinoma (RCC) with a healthy contralateral kidney; however, the current standard for dealing with RCC in patients with a solitary kidney, bilateral tumor and renal or systemic disease inducing a progressive impairment of renal function is nephron-sparing surgery. MATERIALS AND METHODS: Between January 1974 and July 1996, 62 patients (39 men and 23 women, 33-77 years old, mean age 60.6 years) with RCC underwent nephron-sparing surgery. The patients were divided in to two groups according to treatment indication: 46 patients with bilateral tumor (n = 21) or solitary kidney (n = 25) and 16 patients with renal or systemic disease that could damage the contralateral kidney. Survival curves were calculated according to the Kaplan-Meyer method. RESULTS: In the first group 3 patients died postoperatively, and 3 were lost to follow-up; 12 patients (27.9%) had malignant recurrence and 5 (11.6%) died of local recurrence or systemic diffusion. The probability of local or systemic tumor recurrence was 9.9% at 2 years, 20.2% at 5 years and 24.7% at 10 years; the probability of survival was 100% at 2 years, 91.9% at 5 years and 81.9% at 10 years. In the second group 3 patients died of unrelated causes and 1 was lost to follow-up; 4 patients (25%) had a malignant recurrence and 2 (12.5%) died of systemic diffusion of RCC. The probability of tumor recurrence was 13.0% at 2 years, 19.7% at 5 years and 26.4% at 10 years, the probability of survival was 100% at 2 years, 93.3% at 5 years and 86.1% at 10 years. CONCLUSIONS: In our experience nephron-sparing surgery seems justified in patients with a solitary kidney, bilateral tumor or a disease that potentially damages renal function. Tumor diameter and stage, incidental or symptomatic tumor presentation and specific indication for conservative surgery determine the prognosis.
Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
When ureteral length is extensively compromised, preservation of the kidney without recurring to external urinary diversion may be attempted by various techniques. The choice depends on the extension and localization of the defect. We report a technique solution performed in a patient with multiple ureteral tumors and solitary kidney. A 70-years old underwent TURB for superficial bladder cancer and right nephroureterectomy for upper urinary tract tumor. He was admitted for hematuria and renal failure which need a percutaneous nephrostomy. Urography and pielo-RMN showed multiple and irregular defects of proximal left ureter. We performed a left ureterectomy with ureteral substitution by tailored and retroperitonealized ileal segment with simultaneous ileal bladder augmentation. The six months follow-up including serum creatinine, sonography, urodynamic evaluation, urinary cytology, excretory urogram and pielo-RMN shows good results. Ureteral replacement with ileum is indicated only for extensive ureteral diseases in which ureteroneocystostomy or vesical Psoas hitch and/or Boari bladder flap are not feasible. With particular attention to surgical aspects as tailoring ileum (to improve propulsion of urinary bolus, limit the absorbing surface area and decrease mucus formation) and the use of an ileal segment longer than 15 cm (to prevent reflux) and with an accurate patient selection, we think that this procedure can assure satisfactory results also in difficult cases.
Assuntos
Carcinoma Papilar/cirurgia , Nefrectomia , Neoplasias Ureterais/cirurgia , Idoso , Carcinoma Papilar/diagnóstico por imagem , Humanos , Masculino , Radiografia , Neoplasias Ureterais/diagnóstico por imagemRESUMO
The morphology of the mucosa of orthotopic ileal bladders in place for 3 months to 4 years was studied in biopsies obtained at random from 12 patients. A mucosal flattening, a reorganization of the lining epithelium and a disappearance of the fenestrated areas of blood capillaries were found. Enterocytes progressively stratified and acquired poorly differentiated features, along with loss of microvilli, reduction of the apical fuzzy glycocalyx and enlargement of intercellular spaces. Goblet cells at short-term evaluation were actively involved in mucous synthesis and secretion. Metabolic acidosis was slight both in short-term postoperative periods-under alkaline therapy- and in long-term postoperative periods-when therapy was suspended. It can be concluded that, firstly, urine contact determines in such reservoirs a condition of acute irritation and, secondly, environmental changes induce the ileal mucosa to develop a new phenotype probably better suited to a protective rather than absorptive function.
Assuntos
Íleo/transplante , Íleo/ultraestrutura , Mucosa Intestinal/transplante , Mucosa Intestinal/ultraestrutura , Transplante Heterotópico/patologia , Bexiga Urinária/transplante , Bexiga Urinária/ultraestrutura , Idoso , Humanos , Íleo/patologia , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Cirurgia Plástica , Bexiga Urinária/patologiaRESUMO
The purpose of this study was to investigate the accuracy of endorectal coil MRI in the local staging of prostate carcinoma. A total of 73 patients with biopsy-proven prostate carcinoma were examined at 0.5 T prior being submitted to radical prostatectomy. The gold standard was provided in all patients by findings at whole-mount sectioning of the surgical specimens. At pathology 28 patients had stage T2, 30 had stage T3a/b, and 15 had stage T3c lesions. Overall accuracy of endorectal coil MRI in defining local tumor stage was 82% (60 of 73 patients). Of 73 patients, 5 (7%) were underestimated and 8 (11%) overestimated. The sensitivity and the specificity of endorectal coil MRI in diagnosing capsular penetration were 95% and 82%, respectively. Seminal vesicle invasion was detected with 80% sensitivity and 93% specificity. Our data indicate that endorectal coil MRI is an accurate method for local staging of prostate cancer.
Assuntos
Imageamento por Ressonância Magnética , Prostatectomia , Neoplasias da Próstata/patologia , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos , Masculino , Estadiamento de Neoplasias , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Second stage reconfiguration of Camey I neobladder with intact ileal loop was performed in 3 patients due to poor functional results and associated complications requiring reintervention. Neoblasdder capacity increased from a mean volume of 240 to 593 mL, maximum endoluminal pressure decreased from a mean value of 86 to 29 mm water, and night-time incontinence uniformly disappeared. Loop detubularization and reconfiguration, therefore, results in marked improvement of the clinical and urodynamic characteristics of Camey I ileal neobladder.
Assuntos
Incontinência Urinária/cirurgia , Coletores de Urina/métodos , Urodinâmica/fisiologia , Idoso , Humanos , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Reoperação , Neoplasias da Bexiga Urinária/cirurgia , Incontinência Urinária/etiologiaRESUMO
Fifty-six patients with bladder carcinoma were studied with MR imaging for the assessment of the local stage, using the inversion recovery pulse sequence with fat suppression (STIR) with air in the bladder. With this technique images of the inner and the outer parts of the bladder wall were obtained, showing high contrast between the latter and the tumor (tumor/muscle contrast 89.9%). Four tumor stages were recognized: superficial neoplasms (Tis, Ta, and T1), partial wall infiltrating neoplasms (T2); total wall infiltrating neoplasms (T3a, T3b), and neoplasms involving other pelvic organs (T4). MR imaging was compared with histopathologic diagnosis obtained at transurethral resection or cystectomy. True-positive diagnosis was obtained in 80.4%; false-positive in 14.3% of cases; false-negative in 5.3%. Despite the relatively high incidence of overstaged neoplasms, STIR technique combined with air in the bladder allowed a good accuracy in local staging.
Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
Since January 1985, orthotopic ileal bladder substitution after radical cystectomy was performed in 64 male patients. The Camey I procedure was performed in 35 patients (group 1) and the Studer procedure in 29 (group 2). Clinical, metabolic and urodynamic evaluation was performed at regular intervals with a mean follow-up of 27 months for group 1 and 13.6 months for group 2. Patients with a Camey I bladder reconstruction presented smaller capacity and higher intraluminal pressure resulting in shorter voiding intervals and a practically uniform presence of enuresis, as opposed to those reconstructed with the Studer procedure. The incidence of ureteral reflux was also higher in group 1. Metabolic studies in both groups revealed a slight metabolic acidosis which was treated with oral alkalinization. It is concluded that detubularization of the terminal ileum creates a more favorable low-pressure reservoir.
Assuntos
Neoplasias da Bexiga Urinária/cirurgia , Coletores de Urina , Adulto , Idoso , Cistectomia , Seguimentos , Humanos , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/fisiopatologia , UrodinâmicaRESUMO
A case with benign renal leiomyoma examined by all the imaging techniques currently available is described. The aspects were conflicting, particularly with regard to sonography and magnetic resonance imaging, and the sole technique which provided more reliable information was the CT scan.