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1.
Adv Urol ; 2024: 9331738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389652

RESUMO

Objectives: In Japan, caudal block with 1% lidocaine is commonly used for transrectal prostate biopsy. Although 10 mL of 1% lidocaine is commonly used, the appropriate dosage of 1% lidocaine has not been studied. Our hospital routinely uses two different doses (5 or 10 mL) of 1% lidocaine for caudal block for transrectal prostate biopsy. Herein, we retrospectively evaluated the efficacy and safety of both doses of 1% lidocaine. Methods: This retrospective study included 869 patients who underwent transrectal prostate biopsy with caudal block at our hospital. The amount of 1% lidocaine was determined by the day of the week on which the biopsy was performed, and the patient voluntarily chose the day of the biopsy, unaware of the dose of 1% lidocaine used on that day. Pain, anal sphincter tonus, cancer diagnosis rate, and early complications were compared. Results: In total, 466 and 403 patients received 5 and 10 mL of 1% lidocaine for a caudal block, respectively. After propensity-score matching for patient characteristics, each group contained 395 patients. The pain score, anal sphincter tonus score, or prostate cancer diagnosis rate were not significantly different between the two groups. However, rectal bleeding was significantly more frequent and severe in the 10-mL than the 5-mL group (p=0.018 and p=0.0036, respectively). The incidence of other complications was not significantly different between the groups. Conclusions: Our results suggest that 5 mL of 1% lidocaine may be more suitable than 10 mL for caudal block during transrectal prostate biopsy.

2.
Jpn J Clin Oncol ; 54(5): 584-591, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38305451

RESUMO

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.


Assuntos
Antagonistas de Androgênios , Benzamidas , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Nitrilas/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/sangue , Idoso , Estudos Prospectivos , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Compostos de Tosil/administração & dosagem , Compostos de Tosil/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Flutamida/administração & dosagem , Resultado do Tratamento , Anilidas/administração & dosagem , Anilidas/efeitos adversos , Antígeno Prostático Específico/sangue
3.
IJU Case Rep ; 6(5): 293-297, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37667759

RESUMO

Introduction: Ectopic prostatic tissue is prostatic tissue located distant from the prostate gland. Although its existence is not uncommon, the occurrence of adenocarcinoma in ectopic prostatic tissue is rare. Case presentation: A 68-year-old man was suspected to have a nodular-type tumor in the bladder trigone and a tumor in the prostate based on magnetic resonance imaging and cystoscopy results. Transurethral tumor resection and transrectal prostate needle biopsy revealed the coexistence of ectopic prostatic adenocarcinoma in the bladder trigone and low-risk orthotopic prostate cancer. Four years later, the tumor evolved to intermediate-risk prostate cancer during active surveillance, and the patient underwent prostatectomy with resection of the bladder trigone. Pathology indicated no residual ectopic prostatic tissue or adenocarcinoma at the bladder trigone. Conclusion: Adenocarcinoma in ectopic prostatic tissue is very rare; however, when found, the possibility of concurrent cancer in the prostate gland should be considered.

4.
Res Rep Urol ; 15: 395-401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37638329

RESUMO

Radiation-induced hemorrhagic cystitis is a refractory disease that can cause severe hematuria and bladder tamponade. Bladder tamponade due to radiation-induced hemorrhagic cystitis can often recur repeatedly and markedly reduce the quality of life. However, no blood test parameter has been studied yet regarding the prevention of bladder tamponade recurrence. An 84-year-old patient with a history of radiation therapy for cervical cancer was repeatedly hospitalized for bladder tamponade due to radiation-induced hemorrhagic cystitis. At each hospitalization, blood transfusions were performed to treat severe anemia as the first treatment, resulting in hematuria improvement, and the patient was discharged without invasive treatments such as transurethral coagulation. However, anemia developed gradually after each discharge. The anemia progression was obviously unrelated to macrohematuria because macrohematuria did not appear during that period. When the serum hemoglobin level decreased below the physiological range, bladder tamponade recurred. Based on these findings, we posited that the monitoring of the serum hemoglobin level could be useful to predict the occurrence of bladder tamponade. We hypothesized that if the serum hemoglobin level did not fall below the physiological range, bladder tamponade would not occur. We treated chronic anemia after determining its cause and kept serum hemoglobin levels within the physiological range. Since the treatment was initiated, bladder tamponade has not recurred in over 27 months. In this case, the monitoring of the serum hemoglobin level was useful to predict the occurrence of bladder tamponade due to radiation-induced hemorrhagic cystitis. By maintaining serum hemoglobin levels within the physiological range, we successfully prevented the recurrence of bladder tamponade due to radiation-induced hemorrhagic cystitis.

6.
Hinyokika Kiyo ; 68(8): 271-275, 2022 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-36071019

RESUMO

A 74-year-old patient was undergoing treatment for ascending colon cancer (cT4aN2M1a) in the Department of Surgery at our hospital. During treatment for increased lymph node metastasis and spinal metastasis, she complained of numbness in her dorsal thigh. Magnetic resonance imaging showed spinal canal stenosis due to L4 bone metastasis. Immediately after starting radiation therapy for L4 bone metastasis, bladder rupture occurred and led to generalized peritonitis. We performed emergency laparotomy and drainage. Later, the patient's general condition improved, but irreversible neurological symptoms remained, and activities of daily living decreased markedly. This was thought to be caused by weakening of the bladder wall due to chronic cystitis, and hyperextension of the bladder due to neurogenic bladder. Bacteriuria leaked into the abdominal cavity, resulting in generalized peritonitis.


Assuntos
Neoplasias Colorretais , Cistite , Peritonite , Neoplasias da Coluna Vertebral , Atividades Cotidianas , Idoso , Neoplasias Colorretais/complicações , Cistite/complicações , Feminino , Humanos , Peritonite/diagnóstico , Peritonite/etiologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Bexiga Urinária
7.
J Bone Miner Metab ; 40(4): 648-656, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35546371

RESUMO

PURPOSE: To evaluate the utility of vertebral Hounsfield unit (HU) values from computed tomography (CT) in cancer staging as a supplementary screening tool for bone health among prostate cancer (PCa) patients. METHODS: T-scores of bone mineral density (BMD) in each lumbar vertebra (L1-L4) and hip for newly diagnosed PCa patients (N = 139) were measured using dual-energy X-ray absorptiometry (DXA). The degenerative changes in each lumbar vertebra were assessed, and the HU values of trabecular bone in axial CT images of each vertebral body (vertebral CT-HU value) were measured using staging CT. RESULTS: 556 vertebrae were analyzed. 326 of 556 (59%) lumbar vertebrae had degenerative changes. The vertebral CT-HU value was positively correlated with the lumbar BMD T-score, with higher correlation coefficients observed in vertebrae without degenerative changes (r = 0.655, N = 230) when compared to vertebrae with degenerative changes (r = 0.575, N = 326). The thresholds matching BMD T-scores of - 2.0 and - 1.5 set by cancer treatment-induced bone loss guidelines were 95 HU and 105 HU, respectively. Based on the intervention threshold (lumbar BMD T-score < - 1.5), 15.1% of PCa patients required osteoporosis treatment; and, this value increased to 30.9% when L1-L4 CT-HU thresholds that corresponded to BMD T-score < - 1.5 were used. CONCLUSION: Lumbar BMD values from DXA may not reflect true bone health in PCa patients who often have lumbar degenerative diseases. Thresholds based on the vertebral CT-HU value can be used as a supplementary method to identify PCa patients who need anti-osteoporosis drugs.


Assuntos
Densidade Óssea , Neoplasias da Próstata , Absorciometria de Fóton/métodos , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/fisiopatologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
8.
Sci Rep ; 11(1): 21199, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34707147

RESUMO

It is important to identify prognostic and predictive markers of metastatic urothelial carcinoma (mUC) treated with immunocheckpoint inhibitors. We sought to establish a prognostic marker for patients with mUC treated with pembrolizumab based on only blood test results. We included 165 patients with mUC in the discovery cohort and 103 with mUC who were treated with pembrolizumab in the validation cohort. Multivariate and Cox regression analyses were used to analyse the data. In the discovery cohort, the fibrosis-4 index (hazard ratio [HR]: 2.13, 95% confidence interval [CI] 1.20-3.76, p = 0.010), albumin-bilirubin score (HR 1.91, 95% CI 1.27-2.88, p = 0.002), and neutrophil-lymphocyte ratio (HR: 1.84, 95% CI 1.22-2.79, p = 0.004) were independent significant prognostic factors. We established a 'FAN score' that included these three aforementioned items, which were assigned one point each. We divided patients into the 0-1 point (n = 116) and 2-3 points (n = 49) groups. The FAN score was a significant prognostic marker for cancer-specific survival (CSS) (HR 1.48, 95% CI 1.19-1.83, p < 0.001) along with the Eastern Cooperative Oncology Group Performance Status. The FAN score was also a prognostic factor of progression-free survival (PFS) (HR: 1.25, 95% CI 1.01-1.54, p = 0.036) along with the presence of liver metastasis. In the validation cohort, the FAN score was a significant prognostic factor for CSS (HR: 1.48, 95% CI 1.19-1.85, p = 0.001) and PFS (HR: 1.29, 95% CI 1.02-1.62, p = 0.034). We established the FAN score as a prognostic marker for patients with mUC treated with pembrolizumab.


Assuntos
Bilirrubina/sangue , Biomarcadores Tumorais/sangue , Carcinoma/sangue , Neoplasias da Bexiga Urinária/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Fibrose , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Neutrófilos/citologia , Albumina Sérica Humana , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
9.
Hinyokika Kiyo ; 67(1): 7-10, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33535290

RESUMO

An 83-year-old man with left lower back pain was found to have a 5 cm mass in contact with the right adrenal gland and a 12 mm left ureteral stone by abdominal plain computed tomography. An abdominal plain magnetic resonance imaging T2-weighted image revealed a heterogeneous high signal mass in the right adrenal gland. Pheochromocytoma, adrenal carcinoma, and retroperitoneal neurogenic tumor were suspected. Tumor markers and endocrine examinations were within standard values. Laparoscopic right adrenalectomy was performed. A 4×3.6 cm, 62 g solid tumor was found in contact with right adrenal gland. Histopathologically, hobnail-like vascular endothelial cells were found in the tumor, but no malignant findings such as multi-layered vascular endothelial cells and nuclear atypia were observed. This tumorwas diagnosed to be an anastomosing hemangioma.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hemangioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Idoso de 80 Anos ou mais , Células Endoteliais , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Humanos , Masculino , Feocromocitoma/cirurgia
10.
Hinyokika Kiyo ; 61(10): 389-92, 2015 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-26563620

RESUMO

A 76-year-old woman was found to have bilateral suprarenal tumors, 6.5 cm in diameter on the right side, and 2.4 cm in diameter on the left side, by ultrasonography, computed tomography, and magnetic resonance imaging. Strong accumulation of fluorodeoxyglucose in these tumors was found on positron emission tomography. Since it mimicked an adrenal malignant tumor, we performed right adrenalectomy. The pathological diagnosis of the removed mass was benign schwannoma, consistent of the Antoni type A. The left suprarenal tumor was not removed and she has been followed up for 18 months without any recurrence or tumor increase.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neurilemoma/diagnóstico , Neoplasias Retroperitoneais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Imagem Multimodal , Neurilemoma/cirurgia , Tomografia por Emissão de Pósitrons , Neoplasias Retroperitoneais/cirurgia , Tomografia Computadorizada por Raios X
11.
Oncotarget ; 6(25): 21645-54, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26046464

RESUMO

MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and function in tumor development and progression. We previously identified up-regulated miRNAs in clear cell renal cell carcinoma (ccRCC) compared to matched-pair normal kidney by microarray. Here, we identify miRNAs that are up-regulated in ccRCC and are also correlated with survival and/or recurrence. Twenty-four samples from ccRCC patients who underwent nephrectomies between 2011 and 2012 were divided into two groups: one of eleven patients who experienced recurrence (Group 1), and one of thirteen patients with no evidence of disease (Group 2) 2 years after surgery. Analyzing 22 miRNAs that were up-regulated in ccRCC in our previous study, we identify five miRNAs that were statistically up-regulated in Group 1 versus Group 2 by quantitative real-time PCR. We then evaluated these miRNAs in an independent cohort of 159 frozen ccRCC samples. High levels of miR-27a-3p (p < 0.01) correlated with a worse progression-free survival rate. Multivariate analysis revealed that miR-27a-3p was an independent predictive factor for recurrence. For functional analysis, miR-27a-3p controlled cell proliferation, migration and invasion in RCC cell lines. MiR-27a-3p could act as oncogenic miRNA and may be a candidate for targeted molecular therapy in ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Rim/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real
12.
Prostate ; 75(8): 806-14, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25663042

RESUMO

BACKGROUND: Recent studies have reported that bone marrow-derived cells (BMDCs), which are recruited to sites of tissue injury and inflammation, can differentiate into epithelial cells, such as liver, lung, gastrointestinal tract, and skin cells. We investigated the role of BMDCs in contributing to regeneration of injured prostate epithelium. METHODS: Using chimera rats that received allogenic bone marrow grafts from green fluorescent protein (GFP) transgenic rats after lethal whole-body irradiation, we investigated the existence of epithelial marker-positive BMDCs in injured prostate tissue caused by transurethral injection of lipopolysaccharide. RESULTS: Prostate tissues were harvested 2 weeks after transurethral lipopolysaccharide injection. Immunofluorescence staining showed that some cells in the stroma co-expressed GFP and pan-cytokeratin, which suggested the existence of epithelial marker-positive BMDCs. To confirm the existence of such cells, we collected bone marrow-derived non-hematopoietic cells (GFP+/CD45- cells) from the prostate by fluorescence-activated cell sorter analysis and analyzed the characteristics of the GFP+/CD45- cells. The number of cells in this population significantly increased from 0.042% to 0.492% compared with normal prostate tissue. We found by immunofluorescent analysis and RT-PCR that GFP+/CD45- cells expressed cytokeratin, which suggested that these cells have some features of epithelial cells. In the prostate obtained from the chimera rats 34 weeks after lipopolysaccharide injection, GFP- and cytokeratin-positive cells were observed in the prostate gland, which suggested that some of the cells in the prostate gland regenerated after prostate inflammation derived from bone marrow. CONCLUSIONS: BMDCs might be able to differentiate into prostate epithelial cells after prostatic injury.


Assuntos
Transplante de Medula Óssea/métodos , Epitélio/fisiologia , Próstata/citologia , Próstata/fisiologia , Prostatite/patologia , Regeneração/fisiologia , Animais , Células da Medula Óssea/fisiologia , Proteínas de Fluorescência Verde/biossíntese , Masculino , Prostatite/terapia , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Células Estromais , Transplante Homólogo/métodos
13.
Int J Clin Oncol ; 20(1): 156-63, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24740557

RESUMO

BACKGROUND: This study aimed to identify preoperative parameters for predicting cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU). METHODS: The preoperative clinical and laboratory records of 357 UTUC patients who underwent RNU at three different institutions were retrospectively reviewed (256, training set; 101, test set). Univariate and multivariate analyses were performed on the training set data to identify preoperative prognostic factors, using which a risk stratification model was developed. The model was validated using test set data. RESULTS: In univariate analysis, clinical T stage classification and preoperative concentrations of hemoglobin, C-reactive protein, sodium, and albumin showed significant association with CSS. Multivariate analysis showed that low preoperative sodium and hemoglobin concentrations were significantly associated with a poor prognosis. A risk stratification model was developed using the preoperative sodium (<141 mEq/L) and hemoglobin concentrations (below normal). Three subgroups were formed depending on the presence of no (favorable group), one (intermediate), or two (poor) prognostic factors, and the 5-year CSS estimates were found to be 96.5, 75.5, and 47.0 %, respectively (P < 0.01). The risk model was significantly associated with the adverse pathological findings of stage pT3 or more and lymphovascular invasion (P = 0.005). CONCLUSION: We identified low preoperative sodium and hemoglobin concentrations as prognostic factors for patients with UTUC treated with RNU. Our risk stratification model may help physicians design a therapeutic strategy.


Assuntos
Neoplasias Urológicas/patologia , Neoplasias Urológicas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrectomia/métodos , Prognóstico , Estudos Retrospectivos , Risco , Sódio/metabolismo , Neoplasias Urológicas/metabolismo
14.
Prostate ; 74(10): 1052-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24802742

RESUMO

BACKGROUND: Fucosylation is an oligosaccharide modification associated with cancer and inflammation, which is catalyzed by fucosyltransferases. Fucosylated haptoglobin (Fuc-Hpt) has been identified as a novel biomarker for pancreatic cancer. In this study, we evaluated serum Fuc-Hpt as a biomarker for prostate cancer, and investigated the expression of fucosyltransferases and haptoglobin in prostate cancer cell lines. METHODS: We measured the preoperative serum Fuc-Hpt levels in 98 patients who underwent radical prostatectomy (RP) using an established lectin-antibody ELISA. Fucosyltransferase and haptoglobin mRNA and protein expressions in prostate cancer cell lines were determined using quantitative PCR and Western blotting. RESULTS: Serum Fuc-Hpt levels were significantly associated with Gleason score (GS), but not prostate-specific antigen (PSA) levels. The area under the receiver-operator characteristics curve (AUC) for the prediction of GS ≥7 in prostatectomy specimens by Fuc-Hpt was 0.753, in contrast to the PSA AUC of 0.561 and the PSAD AUC of 0.558. The Fuc-Hpt AUC for the prediction of GS upgrade from GS 6 at biopsy to GS ≥7 after RP was 0.689, in contrast to the PSA AUC of 0.588 and PSAD AUC of 0.557. Multivariable analysis revealed that Fuc-Hpt levels were significantly associated with biochemical recurrence after prostatectomy. A high expression of alpha-(1-6) fucosyltransferase (FUT8) and haptoglobin was observed in prostate cancer cell line, suggesting that certain kinds of prostate cancer cells produce Fuc-Hpt. CONCLUSION: Elevated serum Fuc-Hpt level could be a novel cancer biomarker for predicting the prognosis of patients with prostate cancer, particularly those with high GSs.


Assuntos
Biomarcadores Tumorais/sangue , Haptoglobinas/análise , Neoplasias da Próstata/patologia , Idoso , Área Sob a Curva , Linhagem Celular Tumoral , Fucosiltransferases/genética , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue
15.
Int J Urol ; 21(2): 130-4, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23944647

RESUMO

OBJECTIVES: To analyze the presence of immature vessels as a predictive factor of prognosis in patients with renal cell carcinoma. METHODS: Tissue samples were obtained from 50 renal cell carcinoma patients who underwent radical nephrectomy, and the blood vessels were stained using antibodies to cluster of differentiation 34 and α-smooth muscle actin. Immature vessels were defined as those positive for cluster of differentiation 34, and mature vessels as those positive for both cluster of differentiation 34 and α-smooth muscle actin. The extent of vascularization was quantified by calculating the microvessel area and microvessel density. RESULTS: The microvessel area of immature vessels was positively associated with tumor grade (P < 0.0001), T stage (P < 0.0001) and American Joint Committee on Cancer stage (P < 0.0001), and was significantly higher in tumors with metastasis than in those without metastasis (P < 0.0001). The microvessel density did not associate with tumor grade or T stage. The disease-free survival and overall survival were significantly shorter in patients with high microvessel area. CONCLUSIONS: The microvessel area of immature vessels seems to be associated with renal cell carcinoma aggressiveness, suggesting this might be considered as a novel prognostic factor in patients with these tumors.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Microvasos/patologia , Neovascularização Patológica/mortalidade , Neovascularização Patológica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
16.
PLoS One ; 8(9): e74313, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24073208

RESUMO

PURPOSE: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to play crucial roles, including in angiogenesis, in several carcinomas. However, the correlation between EMMPRIN levels and angiogenesis expression profile has not been reported, and the role of EMMPRIN in renal cell carcinoma (RCC) is unclear. In the present study, we evaluated the association of EMMPRIN with angiogenesis, its value in prognosis, and its roles in RCC. EXPERIMENTAL DESIGN: EMMPRIN expression was examined in 50 RCC patients treated with radical nephrectomy. Angiogenesis, proliferation, and invasion activity were evaluated using EMMPRIN knockdown RCC cell lines. The size of EMMPRIN-overexpressing xenografts was measured and the degree of angiogenesis was quantified. EMMPRIN expression was evaluated in RCC patients who received sunitinib therapy and in sunitinib-resistant cells. Further, the relation between EMMPRIN expression and sensitivity to sunitinib was examined. RESULTS: EMMPRIN score was significantly associated with clinicopathological parameters in RCC patients, as well as being significantly correlated with microvessel area (MVA) in immature vessels and with prognosis. Down-regulation of EMMPRIN by siRNA led to decreased VEGF and bFGF expression, cell proliferation, and invasive potential. EMMPRIN over-expressing xenografts showed accelerated growth and MVA of immature vessels. EMMPRIN expression was significantly increased in patients who received sunitinib therapy as well as in sunitinib-resistant 786-O cells (786-suni). EMMPRIN-overexpressing RCC cells were resistant to sunitinib. CONCLUSION: Our findings indicate that high expression of EMMPRIN in RCC plays important roles in tumor progression and sunitinib resistance. Therefore, EMMPRIN could be a novel target for the treatment of RCC.


Assuntos
Basigina/fisiologia , Carcinoma de Células Renais/patologia , Resistencia a Medicamentos Antineoplásicos , Indóis/farmacologia , Neoplasias Renais/patologia , Rim/patologia , Neovascularização Patológica/metabolismo , Pirróis/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Western Blotting , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/mortalidade , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Técnicas Imunoenzimáticas , Rim/efeitos dos fármacos , Rim/metabolismo , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sunitinibe , Células Tumorais Cultivadas
17.
Int J Clin Oncol ; 18(4): 704-10, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22688162

RESUMO

BACKGROUND: A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). METHODS: Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. RESULTS: The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. CONCLUSIONS: The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Docetaxel , Estramustina/administração & dosagem , Estramustina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/uso terapêutico , Resultado do Tratamento
18.
Oncol Lett ; 4(1): 15-21, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22807952

RESUMO

Neoadjuvant chemotherapy (NC) for bladder cancer has been reported to significantly improve the 5-year survival rate. The aim of the present study was to examine the roles of ERCC1 and Snail in determining the response to chemotherapy in bladder cancer treated with NC and radical cystectomy (RC). The expression of the Snail and ERCC1 proteins was determined by immunohistochemical staining of specimens obtained from 58 patients with bladder tumors treated with NC and RC. The correlation between clinical response and the expression of Snail and ERCC1 was investigated. Snail and ERCC1 were co-expressed in 24 (41.4%) of the 58 patients. A marked correlation was found between the expression of Snail and ERCC1 (P=0.001). The co-expression of Snail and ERCC1 was not able to predict pathological complete response (P=0.202). Results of the univariate analysis revealed that the co-expression of Snail and ERCC1 predicted shorter disease-free survival (DFS) and overall survival (OS) than the negative expression of Snail and/or ERCC1. Moreover, the co-expression of ERCC1 and Snail was the only predictive factor for both DFS (P=0.029) and OS (P=0.040). The expression of Snail was correlated with that of ERCC1 and the co-expression of Snail and ERCC1 was the only significant predictive factor of shorter DFS and OS in patients with bladder cancer treated with NC and RC.

19.
Int J Clin Oncol ; 16(6): 660-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21556800

RESUMO

BACKGROUND: Pulmonary metastasectomy in patients with renal cell carcinoma (RCC) remains controversial. The purpose of our analysis was to explore the outcome of patients with RCC who underwent pulmonary metastasectomy at our institution. METHODS: We reviewed data on 25 patients who underwent resection of lung metastasis from 1998 to 2008 at our institution. RESULTS: All patients were treated by radical nephrectomy for primary RCC. Progression-free survival (PFS) ranged from 0.3 to 198.8 months (median 7.4 months), and overall survival (OS) ranged from 2.4 to 198.8 months (median 33.9 months). The 5-year PFS rate was 24.9%, and the OS rate was 35.5%. Although differences in the resectability of the metastasectomy and OS were not significant in univariate or multivariate analyses, the relationship between PFS and the radicality of pulmonary metastasectomy was significant in both the univariate and multivariate analyses (P = 0.004, 0.012, respectively). CONCLUSIONS: The results of pulmonary metastasectomy for patients with RCC at our institution indicate that pulmonary metastasectomy should be performed only when the pulmonary metastasis can be completely resected. Additional studies are therefore necessary to evaluate the prognostic factors and to determine the selection criteria for pulmonary metastasectomy in the new era of molecular-targeted agents.


Assuntos
Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Metastasectomia , Adulto , Idoso , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia , Prognóstico , Resultado do Tratamento
20.
Nihon Hinyokika Gakkai Zasshi ; 102(1): 14-22, 2011 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-21520632

RESUMO

PURPOSE: We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. PATIENTS AND METHODS: We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guérin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. RESULTS: The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p = 0.038). CONCLUSIONS: Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a potential prognostic marker for chemoradiation therapy in invasive bladder cancer.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Proteína bcl-X/análise , Idoso , Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Cisplatino/uso terapêutico , Terapia Combinada , Cistectomia , Feminino , Humanos , Masculino , Invasividade Neoplásica , Prognóstico , Radioterapia Adjuvante , Terapia de Salvação , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia
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