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1.
Am J Kidney Dis ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38514012

RESUMO

RATIONALE & OBJECTIVE: Alport Syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect Type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS. STUDY DESIGN: Retrospective cohort study. SETTING: & Participants: One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA Nephropathy (IgAN). Clinical, genetic, and imaging data were collected from medical records. EXPOSURES: Cystic kidney phenotype evaluated by ultrasonography and defined as the presence of ≥3 cysts in each kidney. Demographic characteristics and eGFR at disease onset. OUTCOMES: Cystic kidney phenotype in the AS and IgAN cohorts. Time to CKD stage 3b and longitudinal changes in eGFR in the AS cohort. ANALYTICAL APPROACH: Logistic regression analysis to test independent strengths of associations of clinical/demographic features with the binary outcome of cystic phenotype. Survival analysis for the outcome of reaching CKD stage 3b and linear mixed models for changes in eGFR over time in the AS cohort. RESULTS: We studied 108 patients with AS; 76 (70%) had genetic diagnosis. Autosomal dominant AS was prevalent, accounting for 68% of patients with genetic diagnosis. Cystic kidney phenotype was observed in 38% of patients with AS and was associated with normal sized kidneys in all but 3 patients, who showed increased total kidney volume, mimicking autosomal dominant polycystic kidney disease (ADPKD). The prevalence of cystic kidney phenotype was significantly higher in patients with AS when compared to comparison group of patients with IgAN (42% vs 19%; p=0.002). Patients with cystic kidney phenotype were older and had more marked reductions in eGFR than patients without cystic changes. Among patients with AS, the cystic phenotype was associated with older age and a faster decline eGFR. LIMITATIONS: Retrospective, single-center study. CONCLUSIONS: Cystic kidney phenotype is a common finding in AS. The cystic kidney phenotype is a common finding in AS suggesting a possible role in cystogenesis for the genetic variants that cause this disease.

2.
Case Rep Oncol ; 17(1): 56-68, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188482

RESUMO

Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs.

3.
Front Oncol ; 12: 937713, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936689

RESUMO

The development of a neuroendocrine phenotype as a mechanism of resistance to hormonal treatment is observed in up to 20% of advanced prostate cancer patients. High grade neuroendocrine prostate cancer (NEPC) is associated to poor prognosis and the therapeutic armamentarium is restricted to platinum-based chemotherapy. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) imaging has recently emerged as a potential new standard for the staging of prostate cancer and PSMA-based radioligand therapy (RLT) as a therapeutic option in advanced metastatic castration resistant prostate cancer (mCRPC). PSMA-based theranostic is not currently applied in the staging and treatment of NEPC since PSMA expression on neuroendocrine differentiated cells was shown to be lost. In this case series, we present 3 consecutive mCRPC patients with histologically proven high grade neuroendocrine differentiation who underwent PSMA-PET/CT and surprisingly showed high tracer uptake. This observation stimulates further research on the use of PSMA-based theranostic in the management of NEPC.

4.
G Ital Nefrol ; 39(3)2022 Jun 20.
Artigo em Italiano | MEDLINE | ID: mdl-35819044

RESUMO

Staphylococcus-associated glomerulonephritis (SAGN) represents a possible version of parainfectious glomerulonephritis and is a pathological entity that's now constantly increasing in developed countries. It is known how bacterial infections can be a possible trigger for various type of glomerulonephritis with clinical onset and evolution comparable to the ones observed in parainfectious glomerulonephritis. Furthermore, in clinical practice the identification and isolation of the pathogenic microorganism responsible for the development of parainfectious glomerulonephritis is not always possible. Therefore, in those cases in which SAGN is suspected, it is often necessary to recur to kidney biopsy in order to come to as much as possible correct diagnosis. Historically, according to scientific literature, the most distinctive anatomopathological feature of SAGN is represented by predominant or codominant mesangial IgA deposits, sometimes associated with C3 deposits. These findings make the differential diagnosis between SAGN and IgA nephropathy often necessary. However, many reports describe how SAGN can also be characterized by a varying spectrum of immunological deposits. In some cases, for example, IgA deposits can be absent and in some other cases it is described a net dominance of C3 deposits. In this case, it becomes extremely important to exclude a possible occurrence of C3 glomerulopathy (C3GN), considering how different are the therapeutic approach and the prognostic implications associated to it. However, the differential diagnosis between SAGN and C3GN can be very hard. Here's a case report about a patient who has been hospitalized into our Unit after developing a form of Staphylococcus Aureus associated glomerulonephritis which presented atypical anatomopathological features.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite , Infecções Estafilocócicas , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico , Humanos , Imunoglobulina A , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Staphylococcus
5.
Monaldi Arch Chest Dis ; 92(1)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34523321

RESUMO

We report a COVID-19 case with acute heart and kidney failure in a healthy young male. Echocardiography showed severe systolic and diastolic left ventricle dysfunction, with diffuse myocardial thickening. Cardiac MRI showed aspects of focal myocarditis, and hypertensive cardiomyopathy. Renal biopsy demonstrated limited acute tubular injury, and hypertensive kidney disease. Coronary angiography excluded critical stenoses. Unlike what we initially suspected, myocardial inflammation had a limited extent in our patient; severe hypertension causing cardiomyopathy and multi-organ damage, not diagnosed before, was primarily responsible for severe illness. Correct diagnosis and guidelines-directed treatment allowed a favorable course.


Assuntos
COVID-19 , Cardiomiopatias , Insuficiência Cardíaca , Hipertensão , Miocardite , COVID-19/complicações , Cardiomiopatias/diagnóstico , Cardiomiopatias/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/complicações , Masculino , Miocardite/diagnóstico por imagem , Miocardite/etiologia
6.
Pathologica ; 113(4): 285-293, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34463673

RESUMO

Multiple myeloma accounts for 10-15% of all hematologic malignancies, and 20% of deaths related to cancers of the blood and bone marrow. Diagnosis is defined by the presence of a serum monoclonal spike (M-spike) of more than 3 g/dL or more than 10% clonal plasma cells in the bone marrow and at least one myeloma-defining event, such as hypercalcemia, anemia, bone lesions, or renal impairment. The kidney is a major target organ, and renal impairment is frequently the first manifestation of the disease. Renal damage occurs in up to 40% of patients and 10-20% will require dialysis. Monoclonal immunoglobulin light chains are the major causes of renal complications in multiple myeloma. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease, AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits, immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components, are constituted by light chain cast nephropathy, light chain proximal tubulopathy, and crystal-storing histiocytosis.We report the case of a 66-year-old woman who presented with albumin-predominant moderate proteinuria and renal failure. Serum and urine immunofixation electrophoresis showed monoclonal κ light chain in both. Renal biopsy confirmed κ-restricted crystal-storing renal disease involving proximal tubular epithelial cells and crystal storing histiocytosis. Multiple myeloma with crystal storing histiocytosis was discovered in bone marrow biopsy. Thus, we present an unusual case of a myeloma patient presenting light chain proximal tubulopathy and crystal-storing histiocytosis both in the kidney and in the bone marrow.


Assuntos
Histiocitose , Nefropatias , Mieloma Múltiplo , Paraproteinemias , Idoso , Feminino , Histiocitose/complicações , Humanos , Rim , Mieloma Múltiplo/complicações , Paraproteinemias/complicações
7.
G Ital Nefrol ; 38(1)2021 Feb 16.
Artigo em Italiano | MEDLINE | ID: mdl-33599424

RESUMO

Waldenström's disease is a rare haematological neoplasm involving B lymphocytes, characterized by medullary infiltrated lymphoplasmacytic lymphoma and by the presence of a monoclonal M paraprotein. Although rarely, this condition may lead to heterogeneous renal involvement and cause severe renal failure. We report the clinical case of a patient with overt nephrotic syndrome in Waldenström's disease treated with a combination chemotherapy (rituximab, cyclophosphamide, dexamethasone) until complete renal and haematological remission.


Assuntos
Síndrome Nefrótica , Macroglobulinemia de Waldenstrom , Ciclofosfamida , Humanos , Rim , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/etiologia , Rituximab , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/tratamento farmacológico
8.
Monaldi Arch Chest Dis ; 91(1)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33501818

RESUMO

Angiosarcoma is a rare malignancy of vascular origin, mostly originating from skin, soft tissues, and breast, but rarely also from the pleura. We present the case of a 55-year-old man who referred to our hospital for a spontaneous bilateral hemothorax. The CT angiography did not show any source of active bleeding; plus, no pleural or lung masses were observable. Cytological and microbiological analyses made on a sample of pleural fluid resulted negative. Despite numerous blood transfusions and thoracenteses, the patient deceased from hemorrhagic shock ten days later and the diagnosis of primary pleural epithelioid angiosarcoma was obtained only by autopsy. Additionally, we present a review of the literature about primary pleural angiosarcomas.


Assuntos
Hemangiossarcoma , Neoplasias Pleurais , Exsudatos e Transudatos , Hemangiossarcoma/complicações , Hemangiossarcoma/diagnóstico , Hemotórax/diagnóstico por imagem , Hemotórax/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pleura , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/diagnóstico por imagem
9.
J Clin Endocrinol Metab ; 105(12)2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32841328

RESUMO

CONTEXT: Apo A-I Leu75Pro is a rare hereditary form of amyloidosis that mainly involves the kidney, the liver, and the testis. OBJECTIVE: To define the characteristics of organ damage and testis impairment in the largest cohort collected to date of men with Apo A-I Leu75Pro amyloidosis. DESIGN, SETTING, AND PATIENTS: Retrospective study from a prospectively collected database of 129 male subjects >18 years with Apo A-I Leu75Pro amyloidosis from a reference center at the University Hospital of Brescia, Italy. MAIN OUTCOME MEASURES: We evaluated liver and renal function, scrotal ultrasound, reproductive hormone levels, testis biopsy, hypogonadal symptoms, and fertility. RESULTS: Progressive involvement of testis, kidney, and liver was observed in 96/129 (74.4%) cases. Testis impairment was found in 88/129 patients (68.2%), liver in 59 (45.7%) and renal in 50 (38.8%). Testis damage was often the first manifestation of the disease and the only dysfunction in 30% of younger patients (<38 years). Testicular involvement was characterized mainly by primary (73/88 patients, 83.0%) and subclinical (8/88, 9.1%) hypogonadism. Almost all (85/88, 96.6%) also had high follicle-stimulating hormone, suggesting a primary global damage of endocrine and spermatogenic functions, and 30% of them did not conceive. Macroorchidism was found in 53/88 (60.2%) patients, especially in men <54 years (30/33, 90.9%). Apo A-I amyloid deposits were found in Sertoli cells, germinal epithelium, and vessel walls. CONCLUSION: In men with Apo A-I Leu75Pro amyloidosis, testicular involvement is the hallmark of the disease, characterized by global primary testicular dysfunction and macroorchidism due to amyloid deposits.


Assuntos
Amiloidose/genética , Apolipoproteína A-I/genética , Mutação de Sentido Incorreto , Doenças Testiculares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Amiloidose/epidemiologia , Amiloidose/patologia , Estudos de Coortes , Bases de Dados Factuais , Predisposição Genética para Doença , Humanos , Itália/epidemiologia , Leucina/genética , Masculino , Pessoa de Meia-Idade , Prolina/genética , Estudos Retrospectivos , Doenças Testiculares/epidemiologia , Doenças Testiculares/patologia , Testículo/patologia , Adulto Jovem
10.
Case Rep Nephrol ; 2020: 8952670, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566333

RESUMO

The relationship between kidneys and anticoagulation is complex, especially after introduction of the direct oral anticoagulants (DOAC). It is recently growing evidence of an anticoagulant-related nephropathy (ARN), a form of acute kidney injury caused by excessive anticoagulation. The pathogenesis of kidney damage in this setting is multifactorial, and nowadays, there is no established treatment. We describe a case of ARN, admitted to our Nephrology Unit with a strong suspicion of ANCA-associated vasculitis due to gross haematuria and haemoptysis; the patient was being given dabigatran. Renal biopsy excluded ANCA-associated vasculitis and diagnosed a red blood cell cast nephropathy superimposed to an underlying IgA nephropathy. Several mechanisms are possibly responsible for kidney injury in ARN: tubular obstruction, cytotoxicity of heme-containing molecules and free iron, and activation of proinflammatory/profibrotic cytokines. Therefore, the patient was given a multilevel strategy of treatment. A combination of reversal of coagulopathy (i.e., withdrawal of dabigatran and infusion of its specific antidote) along with administration of fluids, sodium bicarbonate, steroids, and mannitol resulted in conservative management of AKI and fast recovery of renal function. This observation could suggest a prospective study aiming to find the best therapy of ARN.

11.
Pathology ; 52(3): 297-309, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32107074

RESUMO

Recently cabozantinib, a tyrosine kinase inhibitor with activity against VEGF, MET, AXL, and downregulating cathepsin K in vitro, has been proposed for the treatment of advanced clear and non-clear renal cell carcinomas. Since it is well known that cathepsin K is expressed in the majority of MiT family translocation renal cell carcinomas, we investigated cathepsin K, MET, AXL, and VEGF in a large series of those tumours, looking for possible predictive markers. We collected the clinicopathological features of 34 genetically confirmed MiT family translocation renal cell carcinomas [26 Xp11 and 8 t(6;11) renal cell carcinomas] and studied them using an immunohistochemical panel including PAX8, cathepsin K, HMB45, Melan-A, CD68 (PG-M1), CK7, CA9, MET, AXL and by FISH for VEGFA and MET. Cathepsin K was expressed in 14 of 26, HMB45 in 8 of 25, and Melan-A in 4 of 23 Xp11 renal cell carcinomas, whereas labelling for CK7 and CA9 was minimal. In t(6;11) renal cell carcinoma, cathepsin K and melanogenesis markers were constantly positive, whereas CK7 and CA9 were negative. None of the 34 carcinomas showed CD68 (PG-M1) and AXL expression. One aggressive Xp11 renal cell carcinoma showed increased VEGFA gene copy number (4-5 copies) with concurrent gains of TFE3 and TFEB. None of the 34 carcinomas showed MET gene amplification, whereas staining for MET was found in 7 of 8 t(6;11) and in 16 of 24 Xp11 renal cell carcinomas, and in the latter cases, when the expression was >50%, correlated with aggressiveness (p=0.0049). In Xp11 renal cell carcinomas, the aggressiveness was also correlated with larger tumour size (p=0.0008) and the presence of necrosis (p=0.027) but not nucleolar grading (p=1). Interestingly, in patients with tumours exhibiting two of three parameters (necrosis, larger tumour size and MET immunolabelling >50%) an aggressive clinical behaviour was observed in 88% of cases. In conclusion, cathepsin K, CD68 (PG-M1), CK7, CA9, and PAX8 is a useful panel for the diagnosis. Larger tumour size, the presence of necrosis and MET immunohistochemical expression correlate with aggressive behaviour in Xp11 renal cell carcinomas, especially in combination. VEGF, MET, cathepsin K but not AXL may be potential predictive markers for targeted therapy in MiT family translocation renal cell carcinomas.


Assuntos
Biomarcadores/análise , Carcinoma de Células Renais , Neoplasias Renais , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Catepsina K/metabolismo , Criança , Cromossomos Humanos X/genética , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Translocação Genética , Adulto Jovem , Receptor Tirosina Quinase Axl
12.
Haematologica ; 105(5): 1369-1378, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31399522

RESUMO

MYC translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of MYC have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of MYC increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for MYC, BCL2, and BCL6 rearrangements. We enumerated the number of MYC copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of MYC translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with MYC copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of MYC extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of MYC had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with MYC translocation. The survival of patients with >4 copies, translocation or amplification of MYC seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence in situ hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of MYC.


Assuntos
Linfoma Difuso de Grandes Células B , Proteínas Proto-Oncogênicas c-myc , Linfócitos B , Variações do Número de Cópias de DNA , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética
13.
Clin Genitourin Cancer ; 17(1): e26-e31, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30266249

RESUMO

BACKGROUND: The role of positive surgical margins (PSMs) on the recurrence of renal cell carcinoma (RCC) after partial nephrectomy (PN) is debated, and available evidence lacks long-term data. The aim of this study was to evaluate the predictive role of PSMs on progression-free survival (PFS) in a large cohort followed for at least 5 years. METHODS: This study was a retrospective analysis of a prospectively compiled single-institution database collecting complete information on more than 2700 patients who had undergone surgery for renal tumor. The data of all the patients submitted to PN for RCC and with least 5 years follow-up were extracted. Surgical specimens were examined at the time of surgery only by 2 expert uro-pathologists. A PSM was defined as the presence of cancer cells at the inked surface of the specimen. The role of PSMs on survival was estimated by Cox regression models adjusted for influent covariates. RESULTS: A total of 459 patients fulfilled the inclusion criteria and were evaluated. PSMs were observed in 27 (5.9%) cases. No differences in preoperative and pathologic data were found comparing patients with and without PSMs. At a median follow-up of 96 months (interquartile range, 74-131 months), a clinically evident relapse of RCC was diagnosed in 36 (7.8%) patients at a median interval of 36 months from PN. Among these, 6 had a PSM for an incidence of relapse of 22.2% in the PSM group, whereas 30 had negative margins, for an incidence of 6.9% (P = .013). The sites of relapse were distant organs in 18 cases, and the kidney underwent PN in 21. The patients with PSMs showed a borderline significantly higher incidence of distant metastasis (11.1% vs. 3.5%; P = .071) and a significantly higher incidence of renal relapses (14.8% vs. 3.9%; P = .029). Multivariable Cox models confirmed that the presence of PSMs was an independent predictor of PFS (odds ratio, 3.127; P = .013). CONCLUSIONS: PSMs are an independent predictor of PFS in patients who underwent PN for RCC, owing to a higher incidence of distant and local relapses. Surveillance in presence of PSMs should be intensified and extended for a long time.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Margens de Excisão , Recidiva Local de Neoplasia/mortalidade , Nefrectomia/mortalidade , Néfrons/cirurgia , Tratamentos com Preservação do Órgão/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Néfrons/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
14.
J Robot Surg ; 13(2): 253-260, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30006861

RESUMO

PURPOSE: Prospective randomized trial to compare standard vs delayed approach to dorsal vascular complex (s-DVC vs d-DVC) in robot-assisted radical prostatectomy (RARP). METHODS: Patients scheduled for RARP were randomized into a 1:1 ratio to receive either s-DVC or d-DVC by two experienced surgeons. In s-DVC arm an eight-shaped single stitch was given at the beginning of the procedure and the DVC was subsequently cut at time of apical dissection; in d-DVC arm the plexus was transected at the end of prostatectomy, prior to apex dissection and then sutured. Primary endpoint was difference in estimated blood loss (EBL) and a sample size of 226 cases was calculated; ad interim analysis was planned after 2/3 of recruitment. RESULTS: Endpoint was reached at ad interim analysis after 162 cases (81 s-DVC, 81 d-DVC) and recruitment was, therefore, interrupted. Baseline and tumor characteristics were overlapping. EBL was significantly higher in d-DVC arm (mean EBL 107 vs 65 ml, p = 0.003), but without differences in post-operative hemoglobin, transfusions and complications. Overall PSM rate was higher in d-DVC arm (21.0 vs 14.8%, p = 0.323), with statistical significance relatively to organ-confined disease (15.5 vs 3.6%, p = 0.031). Apical involvement was instead significantly higher in s-DVC arm (prevalence in PSM patients 66.7 vs 23.5%, p = 0.020). Post-operative PSA, continence and potency rates were similar between groups. CONCLUSIONS: Standard and delayed approaches to DVC are safe and lead to similar functional outcomes. A delayed approach exposes to a higher risk of PSM in organ-confined disease but with a lower risk of apical involvement.


Assuntos
Ligadura/métodos , Próstata/cirurgia , Prostatectomia/instrumentação , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Perda Sanguínea Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Fatores de Tempo , Resultado do Tratamento
15.
Endocrine ; 63(3): 592-601, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30367443

RESUMO

PURPOSE: The management of patients with adrenocortical carcinoma (ACC) is challenging. As mitotane and chemotherapy show limited efficacy, there is an urgent need to develop therapeutic approaches. The aim of this study was to investigate the antitumor activity of progesterone and explore the molecular mechanisms underlying its cytotoxic effects in the NCI-H295R cell line and primary cell cultures derived from ACC patients. METHODS: Cell viability, cell cycle, and apoptosis were analyzed in untreated and progesterone-treated ACC cells. The ability of progesterone to affect the Wnt/ß-catenin pathway in NCI-H295R cells was investigated by immunofluorescence. Progesterone and mitotane combination experiments were also performed to evaluate their interaction on NCI-H295R cell viability. RESULTS: We demonstrated that progesterone exerted a concentration-dependent inhibition of ACC cell viability. Apoptosis was the main mechanism, as demonstrated by a significant increase of apoptosis and cleaved-Caspase-3 levels. Reduction of ß-catenin nuclear translocation may contribute to the progesterone cytotoxic effect. The progesterone antineoplastic activity was synergically increased when mitotane was added to the cell culture medium. CONCLUSIONS: Our results show that progesterone has antineoplastic activity in ACC cells. The synergistic cytotoxic activity of progesterone with mitotane provides the rationale for testing this combination in a clinical study.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Humanos , Proteínas de Membrana/metabolismo , Mitotano/uso terapêutico , Cultura Primária de Células , Progesterona/farmacologia , Progestinas/farmacologia , Receptores de Progesterona/metabolismo , beta Catenina/metabolismo
16.
Clin Genitourin Cancer ; 15(5): 540-547, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28533051

RESUMO

BACKGROUND: Poor data are reported on the pathogenesis of ipsilateral relapse (IR) after partial nephrectomy (PN). The objective of this study was to investigate features of IR after PN with the intention to propose a pathogenetic classification. MATERIALS AND METHODS: Retrospective consultation of an institutional database that stores the data of 683 patients submitted to PN since 1993. The clinical, radiological, and follow-up data of the cases submitted to salvage nephrectomy due to an IR were analyzed. The slides of the sections from the tumor-parenchyma interface of PN and the bed of resection from the specimen of nephrectomy were reviewed. RESULTS: Eighteen patients were submitted to salvage nephrectomy for an IR. In 12 cases the IR harbored into the site of PN and a mixture of cancer cells and granulomatous reaction was found at the resection bed (IR type A). In the remaining 6, in microscopy of the resection bed was found only fibrosis: 3 of these cases had a clear-cell renal cell carcinoma (RCC) with diffuse microvascular embolization and the relapse in the same portion of the kidney of the primary tumor (IR type B); the other 3 had a non-clear-cell RCC and the primary and relapsing tumors were located in distinct portions of the kidney (IR type C). Six patients (4 IR type A, 2 type B) had a further progression and 5 of them died due to RCC. CONCLUSION: More frequently an IR is due to the incomplete resection of the primary tumor (IR type A), in a minority of the cases to the local spread of the tumor by microvascular embolization (IR type B), or true multifocality (IR type C). The prognosis of IR not due to multifocality (type A and B) is poor, despite salvage nephrectomy.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/patologia , Idoso , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Nefrectomia , Tratamentos com Preservação do Órgão , Prognóstico , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento
17.
Urol Oncol ; 35(5): 215-220, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28109581

RESUMO

PURPOSE: The surface, intermediate, and basis (SIB) is a system based on surgeon׳s visual assessment of the thickness of healthy parenchyma remaining on the intrarenal portion of the tumor. This system has been proposed to standardize the nomenclature of the resection technique (RT) during partial nephrectomy (PN). Our study aims at evaluating whether the SIB score visually assigned is related to the thickness of parenchyma measured by microscopy. MATERIALS AND METHODS: Data of 52 patients submitted to PN from April to October 2015 were perspectively collected. All the excisions were performed following a "nonanatomical" strategy according to our institutional intention to resect the tumor with a visible margin of parenchyma. After the removal of the specimen, 2 trained examiners applied the SIB system: the intrarenal portion of the nodule was ideally divided into 3 circumferential sectors (surface, intermediate, and basis); on each of these was identified the area covered by the lowest amount of parenchyma (score specific area [SSA]); and a score descriptive of the thickness of parenchyma was assigned to each area. The RT performed (enucleation, enucleoresection, or wedge resection) was defined by the sum of the scores. The same examiners inked every SSAs with a different color and then dedicated pathologists, blinded of the scores assigned, and microscopically measured the parenchyma covering each SSA. The relationship between these values and the SIB scores was assessed. RESULTS: According to the SIB nomenclature, the technique performed was enucleation for 31 patients (60%), enucleoresection for 16 (31%), and wedge resection for 5 (9%). For the surface SSA, the median/mean values of the thickness for S = 0 vs. S = 1 was 0.35/0.84 vs. 2.00/2.26mm and for the intermediate or base SSA, the median/mean value of the thickness for S = 0 vs. 1 vs. 2 was 0.35/0.47 vs. 1.00/1.50 vs. 2.00.5/2.33mm. All the comparison reached statistical significance. CONCLUSIONS: The visual description of the surgical plane followed during PN according to the SIB system is related to the microscopic thickness of healthy parenchyma covering the tumor. The SIB system can correctly discriminate among different R techniques, and therefore could be a crucial tool to standardize the nomenclature of PN.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Margens de Excisão , Nefrectomia/métodos , Tecido Parenquimatoso/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Idoso , Feminino , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Terminologia como Assunto
18.
Minerva Urol Nefrol ; 69(1): 63-68, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28009146

RESUMO

BACKGROUND: The aim of this study was to analyze the rates of positive surgical margins (PSM) after radical prostatectomy in patients undergoing robotic surgery (robot assisted laparoscopic prostatectomy [RALP]) compared with those undergoing open surgery (radical retropubic prostatectomy [RRP]), at an institution with medium case load. METHODS: Retrospective consultation of a perspectively-maintained database that stores the data of all the patients submitted to radical prostatectomy at our institution since 1/2008. The indication to RRP vs. RALP was based almost exclusively on the period of the study: RRP was the sole available option between 1/2008 and 3/2010 and afterwards RALP become the standard of treatment, once a learning curve of 50 cases was concluded. A PSM was defined as the presence of cancer at the inked surface of prostate. A univariate and multivariate binary logistic regression estimated which factors were related to PSMs. RESULTS: The data of 576 patients (285 RRP, 291 RALP) were evaluated. The overall PSM rate was 28.1% (162/414 patients; 20.6% for pT2 stage, 51.8% for pT>2); overall PSM rate for RRP vs. RALP was 31.9% vs. 24.4 % (P=0.044). At multivariable analysis the factors related to the risk of PSM were stage pT>2 (RR 2.979, P=0.001), Gleason Score >6 (RR 1.662, P=0.026), the volume of tumor (RR 1.019, P=0.008) and the surgical technique (RALP vs. RRP, RR 0.647, P=0.039). CONCLUSIONS: In a series from a medium case-load institution, once data are adjusted for local staging, tumor volume and Gleason score, the risk of PSM is lower for RALP than RRP. This evidence could be of support for health-care practitioners to introduce robotic systems.


Assuntos
Margens de Excisão , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
20.
Diagn Interv Radiol ; 22(6): 525-533, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27682741

RESUMO

PURPOSE: We aimed to evaluate the growth pattern and doubling time (DT) of pulmonary adenocarcinomas exhibiting ground-glass opacities (GGOs) on multidetector computed tomography (CT). METHODS: The growth pattern and DT of 22 pulmonary adenocarcinomas exhibiting GGOs were retrospectively analyzed using three-dimensional semiautomatic software. Analysis of each lesion was based on calculations of volume and mass changes and their respective DTs throughout CT follow-up. Three-dimensional segmentation was performed by a single radiologist on each CT scan. The same observer and another radiologist independently repeated the segmentation at the baseline and the last CT scan to determine the variability of the measurements. The relationships among DTs, histopathology, and initial CT features of the lesions were also analyzed. RESULTS: Pulmonary adenocarcinomas presenting as GGOs exhibited different growth patterns: some lesions grew rapidly and some grew slowly, whereas others alternated between periods of growth, stability, or shrinkage. A significant increase in volume and mass that exceeded the coefficient of repeatability of interobserver variability was observed in 72.7% and 84.2% of GGOs, respectively. The volume-DTs and mass-DTs were heterogeneous throughout the follow-up CT scan (range, -4293 to 21928 and -3113 to 17020 days, respectively), and their intra- and interobserver variabilities were moderately high. The volume-DTs and mass-DTs were not correlated with the initial CT features of GGOs; however, they were significantly shorter in invasive adenocarcinomas (P = 0.002 and P = 0.001, respectively). CONCLUSION: Pulmonary adenocarcinomas exhibiting GGOs show heterogeneous growth patterns with a trend toward a progressive increase in size. DTs may be useful for predicting tumor aggressiveness.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Imageamento Tridimensional/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada Multidetectores/métodos , Adenocarcinoma de Pulmão , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Sensibilidade e Especificidade
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