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1.
Urol Oncol ; 41(11): 458.e9-458.e19, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37798145

RESUMEN

OBJECTIVES: Limited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. METHODS: Post-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. RESULTS: Patients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8-16), 14 (11-19), 14 (10-19), 12 (8-24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. CONCLUSIONS: Since renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.


Asunto(s)
Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Axitinib/uso terapéutico , Carcinoma de Células Renales/patología , Antineoplásicos/efectos adversos , Estudios de Cohortes , Neoplasias Renales/patología , Indazoles/efectos adversos , Resultado del Tratamiento
2.
J Med Case Rep ; 17(1): 106, 2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36945070

RESUMEN

BACKGROUND: Abdominal nonfunctional paraganglioma is rare. Malignant potential of paraganglioma is assessed by Grading of Adrenal Pheochromocytoma and Paraganglioma score and genetic testing, but genetic testing is not common. We present a case of abdominal nonfunctional paraganglioma whose malignant potential was assessed by grading of adrenal pheochromocytoma and paraganglioma score and succinate dehydrogenase subunit B staining alternative to genetic testing. CASE PRESENTATION: A 39-year-old Japanese man had a right retroperitoneal tumor without symptoms. Uptake in the tumor was shown by 123I-meta-iodobenzylguanidine scintigraphy. There were no metastases. The results of biochemical workups including blood hormones and urinary metanephrines were normal. We performed retroperitoneoscopic surgery. The tumor was positive for chromogranin A staining but negative for tyrosine hydroxylase. On the basis of the preoperative biochemical workups and pathology results, we diagnosed the tumor as nonfunctional paraganglioma. The Grading of Adrenal Pheochromocytoma and Paraganglioma score classified the tumor as moderately differentiated. Furthermore, negative succinate dehydrogenase subunit B staining suggested the patient has the SDHx (SDHA, SDHB, SDHC and SDHD) mutation. CONCLUSION: Abdominal nonfunctional PGLs are associated with SDHB mutation, and SDHB staining should be performed as a screening.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Masculino , Humanos , Adulto , Feocromocitoma/diagnóstico , Succinato Deshidrogenasa/genética , Succinato Deshidrogenasa/metabolismo , Paraganglioma/diagnóstico , Paraganglioma/genética , Paraganglioma/cirugía , Mutación , Neoplasias de las Glándulas Suprarrenales/patología
3.
Cancer Sci ; 113(8): 2738-2752, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35670054

RESUMEN

Renal cell carcinoma (RCC) features altered lipid metabolism and accumulated polyunsaturated fatty acids (PUFAs). Elongation of very long-chain fatty acid (ELOVL) family enzymes catalyze fatty acid elongation, and ELOVL5 is indispensable for PUFAs elongation, but its role in RCC progression remains unclear. Here, we show that higher levels of ELOVL5 correlate with poor RCC clinical prognosis. Liquid chromatography/electrospray ionization-tandem mass spectrometry analysis showed decreases in ELOVL5 end products (arachidonic acid and eicosapentaenoic acid) under CRISPR/Cas9-mediated knockout of ELOVL5 while supplementation with these fatty acids partially reversed the cellular proliferation and invasion effects of ELOVL5 knockout. Regarding cellular proliferation and invasion, CRISPR/Cas9-mediated knockout of ELOVL5 suppressed the formation of lipid droplets and induced apoptosis via endoplasmic reticulum stress while suppressing renal cancer cell proliferation and in vivo tumor growth. Furthermore, CRISPR/Cas9-mediated knockout of ELOVL5 inhibited AKT Ser473 phosphorylation and suppressed renal cancer cell invasion through chemokine (C-C motif) ligand-2 downregulation by AKT-mTOR-STAT3 signaling. Collectively, these results suggest that ELOVL5-mediated fatty acid elongation promotes not only cellular proliferation but also invasion in RCC.


Asunto(s)
Carcinoma de Células Renales , Elongasas de Ácidos Grasos , Neoplasias Renales , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Proliferación Celular/genética , Elongasas de Ácidos Grasos/genética , Ácidos Grasos , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Proteínas Proto-Oncogénicas c-akt
4.
J Geriatr Oncol ; 13(1): 88-93, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34238726

RESUMEN

BACKGROUND: We used real-world and large-scale data to assess the clinical efficacy and safety of pembrolizumab in older patients with advanced urothelial carcinoma (UC). METHODS: A total of 608 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. All patients were histologically diagnosed with pure UC. Using propensity score matching (PSM) (ECOG performance status, site of metastasis, hemoglobin level and neutrophil-to-lymphocyte ratio, 1:1 matching), the overall survival (OS) and adverse events (AEs) of patients <75 and ≥75 years old were compared. RESULTS: The median follow-up (IQR) period was 16.1 (9.9-20.5) months. After PSM, there were 215 patients each in the aged <75 years and aged ≥75-year-old groups. The median OS of all patients was estimated to be 10.4 months (95% confidence interval [CI] = 8.8-12.1). After PSM, the median OS was 7.8 months (95% CI = 5.2-10.4) in the <75-year-old group and 10.4 months (95% CI = 7.3-13.5) in the ≥75-year-old group (P = 0.186). Any-grade AEs were more frequently reported in the ≥75-year-old group in comparison to the age <75-year-old group (55.3% vs. 41.9%, P = 0.007), whereas there was no significant difference between the two groups in the incidence of grade ≥3 AEs (10.2% vs. 12.6%, P = 0.544). The objective response rate, defined as complete remission or a partial response, was 22.8% in the <75-year-old group and 25.1% in the ≥75-year-old group (P = 0.651). CONCLUSIONS: The present study demonstrates that age does not affect the efficacy and safety of pembrolizumab treatment for advanced chemoresistant UC. Pembrolizumab treatment should not be avoided based on chronological age; however, close monitoring for the development of treatment-related AE should be considered for older patients.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Anciano , Carcinoma de Células Transicionales/tratamiento farmacológico , Resistencia a Antineoplásicos , Humanos , Puntaje de Propensión , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
5.
Cancer Immunol Immunother ; 71(2): 461-471, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34235546

RESUMEN

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunoterapia/mortalidad , Linfocitos/patología , Neutrófilos/patología , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/inmunología
6.
Oncol Rep ; 47(2)2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34841437

RESUMEN

Renal cell carcinoma (RCC) is an aggressive genitourinary malignancy which has been associated with a poor prognosis, particularly in patients with metastasis, its major subtypes being clear cell RCC (ccRCC), papillary PCC (pRCC) and chromophobe RCC (chRCC). The presence of intracellular lipid droplets (LDs) is considered to be a hallmark of ccRCC. The importance of an altered lipid metabolism in ccRCC has been widely recognized. The elongation of very­long­chain fatty acid (ELOVL) catalyzes the elongation of fatty acids (FAs), modulating lipid composition, and is required for normal bodily functions. However, the involvement of elongases in RCC remains unclear. In the present study, the expression of ELOVL2 in ccRCC was examined; in particular, high levels of seven ELOVL isozymes were observed in primary tumors. Of note, elevated ELOVL2 expression levels were observed in ccRCC, as well as in pRCC and chRCC. Furthermore, a higher level of ELOVL2 was significantly associated with the increased incidence of a poor prognosis of patients with ccRCC and pRCC. The CRISPR/Cas9­mediated knockdown of ELOVL2 resulted in the suppression of the elongation of long­chain polyunsaturated FAs and increased LD production in renal cancer cells. Moreover, ELOVL2 ablation resulted in the suppression of cellular proliferation via the induction of apoptosis in vitro and the attenuation of tumor growth in vivo. On the whole, the present study provides new insight into the tumor proliferation mechanisms involving lipid metabolism, and suggests that ELOVL2 may be an attractive novel target for RCC therapy.


Asunto(s)
Apoptosis/genética , Carcinoma de Células Renales/genética , Elongasas de Ácidos Grasos/genética , Neoplasias Renales/genética , Metabolismo de los Lípidos/genética , Sistemas CRISPR-Cas , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Renales/patología
7.
Hinyokika Kiyo ; 67(6): 233-238, 2021 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-34265898

RESUMEN

Renal mucinous tubular and spindle cell carcinoma (MTSCC) is a rare kidney cancer subtype with limited cases reported in the literature. Renal MTSCC has many similarities with papillary renal cell carcinoma (pRCC), and it is therefore often difficult to make a differential diagnosis between them. Herein, we report a case of renal MTSCC. The patient was a 76-year-old woman. Computed tomography revealed a left renal tumor. Magnetic resonance imaging (MRI) demonstrated an iso-intensity or high signal intensity mass on T2-weighted images, high signal intensity on diffusion-weighted images, and weak and gradual enhancement. We diagnosed the patient with left renal cell carcinoma (cT1bN0M0) and performed laparoscopic left nephrectomy in May 2019. The histopathological diagnosis was renal MTSCC. Six months after surgery, the patient remains free of recurrence and of metastasis. MRI is effective for the preoperative differentiation of renal MTSCC from pRCC since renal MTSCC presents an iso-intensity or high signal intensity on MRI T2-weighted images reflecting the mucin component in the intervening stroma within the tumor.


Asunto(s)
Adenocarcinoma Mucinoso , Carcinoma de Células Renales , Neoplasias Renales , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/cirugía , Anciano , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Recurrencia Local de Neoplasia , Nefrectomía
8.
Cancer Sci ; 112(9): 3616-3626, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34145921

RESUMEN

The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Modelos Estadísticos , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/sangre , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Hemoglobinas/análisis , Humanos , Japón/epidemiología , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Supervivencia sin Progresión , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Medición de Riesgo
10.
Cancer Sci ; 112(4): 1524-1533, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33159829

RESUMEN

Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens.


Asunto(s)
Hormonas/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Anciano , Antagonistas de Andrógenos/uso terapéutico , Biopsia/métodos , Humanos , Japón , Masculino , Estadificación de Neoplasias/métodos , Pronóstico , Supervivencia sin Progresión , Neoplasias de la Próstata/tratamiento farmacológico , Estudios Retrospectivos
11.
Cancer Sci ; 111(7): 2460-2471, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32402135

RESUMEN

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.


Asunto(s)
Antineoplásicos/uso terapéutico , Axitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Axitinib/administración & dosificación , Axitinib/efectos adversos , Carcinoma de Células Renales/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Curva ROC , Retratamiento , Resultado del Tratamiento
12.
BJUI Compass ; 1(5): 165-173, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35475210

RESUMEN

Objectives: To evaluate the association between the use of local radiotherapy (RT) with the survival of patients with de novo metastatic prostate cancer and symptomatic local events (SLEs). Patients and methods: Patients were initially diagnosed with metastatic prostate cancer between 2008 and 2017 at 30 institutes in Japan. Prostate-specific antigen (PSA) progression-free survival (PSA-PFS) under initial androgen deprivation therapy and overall survival (OS) was compared between patients receiving local RT (RT group) and no RT (no-RT group) by multivariate Cox proportional hazard analyses. The occurrence rate of grade ≥2 SLEs was compared by multivariate logistic regression analyses. Propensity score matching (PSM) analyses were performed to compare PSA-PFS and OS of the groups in the high and low metastatic burden cohort. Results: Two hundred and five (7%) of 2829 patients received RT before PSA progression. Median PSA-PFS and OS were significantly longer in the RT group than in the no-RT group and the difference was significant in multivariate analyses (HR = 0.44, 95% CI = 0.33-0.57 and HR = 0.40, 95% CI = 0.27-0.60, respectively). The occurrence rate of grade ≥2 SLEs was significantly lower in the RT group (2%) than the no-RT group (9%) and the difference was significant in multivariate analyses (HR = 0.28, 95% CI = 0.10-0.76). Using PSM analyses, PSA-PFS and OS remained significantly different (HR = 0.64, 95% CI = 0.46-0.89 and HR = 0.47, 95% CI = 0.30-0.72, respectively), between the RT (n = 182) and the no-RT (n = 182) groups. The difference in OS was significant in the high metastatic burden cohort (HR = 0.55, 95% CI = 0.37-0.81). Conclusions: Addition of local RT to standard treatment for de novo metastatic prostate cancer patients tends to have the potential to extend survival, even in patients with high metastatic burden, and to reduce SLEs.

13.
Oncol Lett ; 17(1): 1203-1210, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30655885

RESUMEN

p16INK4a (p16) is a key molecule in bladder tumor (BT) development. We previously reported that a p16 antitumor peptide inhibited the growth of subcutaneous BT grafts in mice through restoration of p16 function using a Wr-T peptide transporter system. In the present study, the efficacy of mouse p16 peptide administration in a mouse lung metastasis model for BT and also the toxicity of peptides by cardiac peptide injection were evaluated. Mouse lung metastases were developed by tail vein injection of a p16-deficient MBT-2 cell line. Six-week-old C3H/He female mice were divided into three groups: A control group (n=12) receiving no treatment; a group treated once on the 3rd experimental day (n=12); and a group treated three times on the 3rd, 5th and 7th experimental days (n=10) with an injection of a mixture of 80 nmol mouse p16 peptide and 50 nmol Wr-T into the tail vein. At the 14th experimental day, the lung metastases were histologically evaluated. Lung metastases were observed in 100% (12/12), 41.7% (5/12) and 30% (3/10) of the aforementioned three groups, respectively. The number and area of metastatic lung tumors were significantly different between control and treatment groups (control vs. triple treatment group for the number and area, P=0.0029 and P=0.0296, respectively). Immunohistochemistry demonstrated that phosphorylated retinoblastoma (Rb) protein was decreased in lung tumors of the treatment groups, compared with the control group. The toxicity of p16 peptide transduction was evaluated by using low-dose treatment (three dosages) and high-dose treatment (two dosages) on three male and three female C3H/He mice in early and late experimental phases. In low and high dose groups, no notable change was determined in body weight or blood analyses in early or late phases following mouse p16 peptide administration. In addition, no notable change was observed histologically in bone marrow of treatment groups. To conclude, systemic p16 peptide administration decreased lung tumor development in a mouse metastatic BT model without severe adverse events, as assessed by blood analyses and histological evaluation.

14.
Int J Urol ; 26(3): 334-340, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30690817

RESUMEN

Radical cystectomy remains the gold standard for treatment of muscle-invasive bladder cancer. Robot-assisted radical cystectomy has technical advantages over laparoscopic radical cystectomy and has emerged as an alternative to open radical cystectomy. Despite the advancements in robotic surgery, experience with total intracorporeal reconstruction of urinary diversion remains limited. Most surgeons have carried out the hybrid approach of robot-assisted radical cystectomy and extracorporeal reconstruction of urinary diversion, as intracorporeal reconstruction of urinary diversion remains technically challenging. However, intracorporeal reconstruction of urinary diversion might potentially proffer additional benefits, such as decreased fluid loss, reduction in estimated blood loss and a quicker return of bowel function. The adoption of intracorporeal ileal neobladder reconstruction has hitherto been limited to high-volume academic institutions. In the present review, we compare the totally intracorporeal robot-assisted radical cystectomy approach with open radical cystectomy and robot-assisted radical cystectomy + extracorporeal reconstruction of urinary diversion in muscle-invasive bladder cancer patients.


Asunto(s)
Cistectomía/métodos , Recurrencia Local de Neoplasia/prevención & control , Complicaciones Posoperatorias/prevención & control , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Derivación Urinaria/métodos , Pérdida de Sangre Quirúrgica/prevención & control , Cistectomía/efectos adversos , Enfermedad , Mortalidad Hospitalaria , Humanos , Íleon/cirugía , Estimación de Kaplan-Meier , Márgenes de Escisión , Invasividad Neoplásica , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Procedimientos Quirúrgicos Robotizados/efectos adversos , Vejiga Urinaria/patología , Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Derivación Urinaria/efectos adversos
15.
Cancer Sci ; 109(6): 1865-1875, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29660846

RESUMEN

A hallmark of clear cell renal cell carcinoma (ccRCC) is the presence of intracellular lipid droplets (LD) and it is assumed that phosphatidic acid (PA) produced by phospholipase D (PLD) plays some role in the LD formation. However, little is known about the significance of PLD in ccRCC. In this study, we examined the expression levels of PLD in ccRCC. The classical mammalian isoforms of PLD are PLD1 and PLD2, and the levels of both mRNA were higher at the primary tumor sites than in normal kidney tissues. Similarly, both PLD were significantly abundant in tumor cells as determined by analysis using immunohistochemical staining. Importantly, a higher level of PLD was significantly associated with a higher tumor stage and grade. Because PLD2 knockdown effectively suppressed the cell proliferation and invasion of ccRCC as compared with PLD1 in vitro, we examined the effect of PLD2 in vivo. Notably, shRNA-mediated knockdown of PLD2 suppressed the growth and invasion of tumors in nude mouse xenograft models. Moreover, the higher expression of PLD2 was significantly associated with poorer prognosis in 67 patients. As for genes relating to the tumor invasion of PLD2, we found that angiogenin (ANG) was positively regulated by PLD2. In fact, the expression levels of ANG were elevated in tumor tissues as compared with normal kidney and the inhibition of ANG activity with a neutralizing antibody significantly suppressed tumor invasion. Overall, we revealed for the first time that PLD2-produced PA promoted cell invasion through the expression of ANG in ccRCC cells.


Asunto(s)
Carcinoma de Células Renales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , Fosfolipasa D/genética , Ribonucleasa Pancreática/genética , Anciano , Animales , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Células HEK293 , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Ratones Desnudos , Persona de Mediana Edad , Fosfolipasa D/metabolismo , Interferencia de ARN , Tratamiento con ARN de Interferencia/métodos , Ribonucleasa Pancreática/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Sci Rep ; 8(1): 5918, 2018 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-29651113

RESUMEN

Lymph node metastasis is one of the most important factors for tumor dissemination. Quantifying microRNA (miRNA) expression using real-time PCR in formalin-fixed, paraffin-embedded (FFPE) lymph node can provide valuable information regarding the biological research for cancer metastasis. However, a universal endogenous reference gene has not been identified in FFPE lymph node. This study aimed to identify suitable endogenous reference genes for miRNA expression analysis in FFPE lymph node. FFPE lymph nodes were obtained from 41 metastatic cancer and from 16 non-cancerous tissues. We selected 10 miRNAs as endogenous reference gene candidates using the global mean method. The stability of candidate genes was assessed by the following four statistical tools: BestKeeper, geNorm, NormFinder, and the comparative ΔCt method. miR-103a was the most stable gene among candidate genes. However, the use of a single miR-103a was not recommended because its stability value exceeded the reference value. Thus, we combined stable genes and investigated the stability and the effect of gene normalization. The combination of miR-24, miR-103a, and let-7a was identified as one of the most stable sets of endogenous reference genes for normalization in FFPE lymph node. This study may provide a basis for miRNA expression analysis in FFPE lymph node tissue.


Asunto(s)
Metástasis Linfática/genética , MicroARNs/genética , Neoplasias/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Formaldehído , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Masculino , MicroARNs/clasificación , Persona de Mediana Edad , Neoplasias/clasificación , Neoplasias/patología , Adhesión en Parafina , Fijación del Tejido
18.
Jpn J Clin Oncol ; 47(3): 252-256, 2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-27980085

RESUMEN

OBJECTIVES: The aim of this study was to compare 29 muscle-invasive bladder cancer patients who received neoadjuvant chemotherapy (NAC) followed by immediate robot-assisted radical cystectomy (RARC) with those who underwent minimum-incision endoscopic RC (MIE-RC). METHODS: We retrospectively reviewed the charts of 430 consecutive patients who underwent RC and bilateral pelvic node dissection (PLND) between May 1994 and July 2016. Our study focused on patients with MIBC who had histologically confirmed stage T2-T4aN0M0 urothelial carcinoma of the bladder and received NAC prior to surgery. Accordingly, 225 patients were included in this analysis, of whom, 29 underwent RARC (RARC group) and 196 underwent MIE-RC (MIE-RC group). The primary endpoints in this study were the positive surgical margin (PSM) rate and lymph node (LN) count. RESULTS: In the RARC group, 20 patients underwent RARC with intracorporeal urinary diversion and nine patients underwent RARC with extracorporeal urinary diversion. The median surgical duration for RC and bilateral PLND was 125 min in the RARC group and 98 min in the MIE-RC group (P < 0.001). The rate of PSM was 0% in the RARC group and 0.5% in the MIE-RC group. The median LN counts were 15 in the RARC group and 18 in the MIE-RC group. No intra-operative complication or mortality was associated with RARC or MIE-RP. All complications were grade 2 according to the Clavien-Dindo classification. CONCLUSIONS: Our initial experience with NAC followed by RARC appears to be favorable, with acceptable operative and perioperative clinical outcomes when compared with those of MIE-RC.


Asunto(s)
Cistectomía/métodos , Terapia Neoadyuvante/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Cistectomía/efectos adversos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Robótica , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/patología
19.
Prostate Int ; 4(4): 140-144, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27995113

RESUMEN

BACKGROUND: We retrospectively analyzed castration-resistant prostate cancer (CRPC) patients treated with secondary hormonal therapies (SHTs) prior to docetaxel therapy. METHODS: The cases of 73 CRPC patients who underwent docetaxel therapy in 2005-2011 at four hospitals in Ibaraki, Japan were analyzed. We determined the cause-specific survival (CSS) from the start of docetaxel therapy and the time point of CRPC diagnosis, and we compared the CSS achieved with/without prior classical SHTs, which were defined as low-dose steroid and estramustine phosphate. RESULTS: Of the 73 enrolled patients, 26 underwent docetaxel therapy (DOC group), and 47 underwent SHTs (SHTs-DOC group) as the initial treatment for CRPC. In the docetaxel therapy, the rate of prostate-specific antigen responses were higher in the DOC group compared with the SHTs-DOC group (76.9% vs. 44.7%, P = 0.0066). The median CSS from the docetaxel therapy initiation was not significant but longer in the DOC group than in the SHTs-DOC group (23.4 months vs. 16.6 months, P = 0.0969). However, the median CSS from the time of CRPC diagnosis did not significantly differ between the DOC and SHTs-DOC groups (23.4 months vs. 24.7 months, P = 0.9233). In a univariate analysis, pain and visceral metastasis appeared to be risk factors for the CSS in the SHTs-DOC group. The patients with pain and/or visceral metastasis had significantly poorer survival than those without these factors in the SHTs-DOC group (31.5 months vs. 16.8 months, P = 0.0053). CONCLUSION: The induction of SHTs prior to docetaxel therapy is an acceptable treatment option with some survival benefits for CRPC patients without pain and visceral metastases.

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