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1.
J Immunol ; 213(1): 23-28, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38758119

RESUMEN

Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p = 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p = 0.024) and improving cancer-specific survival compared with the low group (p = 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC.


Asunto(s)
Carcinoma de Células Renales , Genotipo , Antígenos HLA , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/inmunología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Antígenos HLA/genética , Antígenos HLA/inmunología , Nivolumab/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/genética , Adulto , Anciano de 80 o más Años
2.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-34949714

RESUMEN

The interaction of signal regulatory protein α (SIRPα) on macrophages with CD47 on cancer cells is thought to prevent antibody (Ab)-dependent cellular phagocytosis (ADCP) of the latter cells by the former. Blockade of the CD47-SIRPα interaction by Abs to CD47 or to SIRPα, in combination with tumor-targeting Abs such as rituximab, thus inhibits tumor formation by promoting macrophage-mediated ADCP of cancer cells. Here we show that monotherapy with a monoclonal Ab (mAb) to SIRPα that also recognizes SIRPß1 inhibited tumor formation by bladder and mammary cancer cells in mice, with this inhibitory effect being largely dependent on macrophages. The mAb to SIRPα promoted polarization of tumor-infiltrating macrophages toward an antitumorigenic phenotype, resulting in the killing and phagocytosis of cancer cells by the macrophages. Ablation of SIRPα in mice did not prevent the inhibitory effect of the anti-SIRPα mAb on tumor formation or its promotion of the cancer cell-killing activity of macrophages, however. Moreover, knockdown of SIRPß1 in macrophages attenuated the stimulatory effect of the anti-SIRPα mAb on the killing of cancer cells, whereas an mAb specific for SIRPß1 mimicked the effect of the anti-SIRPα mAb. Our results thus suggest that monotherapy with Abs to SIRPα/SIRPß1 induces antitumorigenic macrophages and thereby inhibits tumor growth and that SIRPß1 is a potential target for cancer immunotherapy.


Asunto(s)
Antineoplásicos Inmunológicos/farmacología , Antineoplásicos/farmacología , Inmunoterapia/métodos , Macrófagos/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/metabolismo , Animales , Anticuerpos Monoclonales/farmacología , Antígeno CD47/metabolismo , Línea Celular Tumoral , Ratones , Receptores de Superficie Celular/genética , Receptores Inmunológicos/genética , Rituximab , Resultado del Tratamiento , Vejiga Urinaria
3.
Int J Clin Oncol ; 29(6): 640-646, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38625439

RESUMEN

In the field of urology, robotic surgery has gained rapid and wide acceptance as a standard surgical approach in the majority of major surgeries over the last decade. To date, the da Vinci surgical system has been the dominant platform in robotic surgery; however, several newly developed robotic systems have recently been introduced in routine clinical practice. Of these, hinotori, the first made-in-Japan robotic system, is characterized by various unique and attractive features different from the existing system, and the use of this system has gradually increased mainly in urologic cancer surgeries, including radical prostatectomy, partial nephrectomy, radical nephrectomy, and radical nephroureterectomy. This review initially describes detailed characteristics of hinotori, then summarizes the early experience with urologic cancer surgeries using hinotori at our institution, and finally discusses the future prospects of robotic surgery using hinotori, considering problems associated with the use of this robotic system.


Asunto(s)
Prostatectomía , Procedimientos Quirúrgicos Robotizados , Neoplasias Urológicas , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/instrumentación , Neoplasias Urológicas/cirugía , Prostatectomía/métodos , Prostatectomía/instrumentación , Nefrectomía/métodos , Nefrectomía/instrumentación , Procedimientos Quirúrgicos Urológicos/instrumentación , Procedimientos Quirúrgicos Urológicos/métodos , Nefroureterectomía/métodos , Masculino
4.
Endocr J ; 71(1): 65-74, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-37952980

RESUMEN

Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that secrete catecholamines and arise from the adrenal medulla or extra-adrenal sympathetic ganglia. These tumors secrete adrenaline and noradrenaline, but paragangliomas usually produce only noradrenaline because of the lack of phenylethanolamine N-methyltransferase (PNMT) expression. Composite paragangliomas, which are complex tumors consisting of multiple types of neuroblastic cells, are extremely rare. We present the case of a 46-year-old woman with an atypical catecholamine profile who was preoperatively diagnosed with pheochromocytoma. However, postoperative pathology revealed that the patient had an extra-adrenal paraganglioma accompanied by a ganglioneuroma, which led to the diagnosis of a composite tumor. Interestingly, PNMT is expressed in both paragangliomas and ganglioneuromas. In addition, we reviewed reported composite paragangliomas and compared their clinical features with those of composite pheochromocytomas. We also discuss various aspects of the etiology of composite paragangliomas and the mechanism by which PNMT is expressed in tumors.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Ganglioneuroma , Paraganglioma , Feocromocitoma , Femenino , Humanos , Persona de Mediana Edad , Catecolaminas/metabolismo , Feocromocitoma/diagnóstico , Feocromocitoma/cirugía , Feocromocitoma/patología , Ganglioneuroma/diagnóstico , Ganglioneuroma/cirugía , Feniletanolamina N-Metiltransferasa , Paraganglioma/diagnóstico , Paraganglioma/cirugía , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias de las Glándulas Suprarrenales/patología , Norepinefrina
5.
Int J Urol ; 31(5): 459-463, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38239011

RESUMEN

Prostatitis is a major urological disease affecting 25%-50% of men over their lifetime. However, prostatitis is often overlooked in nonurologic departments due to its sometimes indeterminate symptoms. In this review, we describe how to recognize and treat acute bacterial prostatitis, which manifests as a clinical problem in other departments as well as urology, to help prevent this disease from being overlooked. There are several possible negative effects of not recognizing acute bacterial prostatitis (ABP). First, initial treatment can fail. In the hyperacute phase, common antibiotics are often effective, but in rare cases, such antibiotics may not be effective. In addition, once ABP progresses to form a prostate abscess, potentially avoidable surgical interventions are often needed. A second issue is the transition to chronic prostatitis. If chronic bacterial prostatitis progresses, treatment requires long-term antibiotic administration and the response rate is not high. Some patients may have to deal with urinary tract infections for the rest of their lives. Finally, there is the problem of overlooking the underlying disease. ABP is rare in healthy adult men without underlying disease, including sexually transmitted diseases as well as benign prostatic hyperplasia, urinary stones, and malignant tumors, and may not be obvious. When examining patients with fever of unknown origin, it is necessary to exclude not only infectious diseases but also collagen diseases and malignant tumors. If there are any doubts, we recommend a rectal exam and consultation with a urologist.


Asunto(s)
Antibacterianos , Prostatitis , Humanos , Masculino , Prostatitis/complicaciones , Prostatitis/microbiología , Prostatitis/diagnóstico , Enfermedad Aguda , Antibacterianos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/complicaciones , Enfermedad Crónica
6.
Int J Urol ; 31(1): 39-44, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37743534

RESUMEN

OBJECTIVES: We evaluate the effect of myosteatosis on new-onset diabetes mellitus after kidney transplantation. METHODS: Consecutive patients who had renal transplant between 2006 and 2021 were reviewed, and 219 patients were finally included. Psoas muscle index was used to evaluate sarcopenia and average total psoas density (calculated by computed tomography before surgery) for myosteatosis. We used Cox proportional regression analyses in investigation of whether skeletal muscle depletion before surgery inclusive of sarcopenia and myosteatosis is a new additional predictor of new-onset diabetes mellitus. RESULTS: Median recipient age and body mass index were 45 years and 21.1 kg/m2 , respectively, and 123 patients (56%) were male. Preoperative impaired glucose tolerance was present in 58 patients (27%) and new-onset diabetes mellitus in 30 patients (14%), with median psoas muscle index of 6 cm2 /m2 and average total psoas density of 41 Hounsfield Unit. In multivariate analysis, significant risk factors were body mass index ≥25 kg/m2 (p < 0.01), impaired glucose tolerance (p < 0.01), and average total psoas density < 41.9 Hounsfield Unit (p = 0.03). New-onset diabetes mellitus had incidence rates of 3.7% without risk factors, 10% with a single risk factor, 33% with two, and 60% with three. Patients with new-onset diabetes mellitus were effectively stratified by the number of risk factors (p < 0.01). CONCLUSIONS: Myosteatosis could be a new risk factor used to predict new-onset diabetes mellitus.


Asunto(s)
Diabetes Mellitus , Intolerancia a la Glucosa , Trasplante de Riñón , Sarcopenia , Humanos , Masculino , Femenino , Sarcopenia/diagnóstico por imagen , Sarcopenia/epidemiología , Sarcopenia/etiología , Intolerancia a la Glucosa/etiología , Intolerancia a la Glucosa/complicaciones , Trasplante de Riñón/efectos adversos , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Músculo Esquelético , Músculos Psoas/diagnóstico por imagen , Músculos Psoas/patología , Estudios Retrospectivos
7.
Int J Urol ; 31(7): 795-801, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38622823

RESUMEN

OBJECTIVES: This study aimed to investigate perioperative complications and the details of postoperative ureteral stricture after ureteroscopy with laser lithotripsy (URS-L) for upper urinary tract stones in Japan. METHODS: Patient data on intra- and postoperative complications after ureteroscopy using URS-L were retrospectively collected from multiple centers in Japan between April 2017 and March 2020 with the cooperation of the Japanese Society of Endourology and Robotics. Data included the number of patients undergoing URS-L, number and type of intra- and postoperative complications, and detailed characteristics of postoperative ureteral stricture. RESULTS: In total, 14 125 patients underwent URS-L over 3 years at 82 institutions. Annual URS-L numbers gradually increased from 4419 in 2017, to 4760 in 2018, and 4946 in 2019. The total complication rate was 10.5%, which was divided into intra-operative complications in 1.40% and postoperative complications in 9.18%. The annual incidences of intra- and postoperative complications were not significantly different from year to year (p = 0.314 and p = 0.112). Ureteral perforation, ureteral avulsion, and the intra-operative conversion rate were 1.35%, 0.03%, and 0.02%, respectively. Fever >38°C, septic shock, blood transfusion, and postoperative mortality were 7.44%, 0.81%, 0.07%, and 0.04%, respectively. Ureteral stricture occurred in 0.8% of cases. The median length of stricture site was 10.0 mm and the success rate of stricture treatment was 54.6%. CONCLUSION: Although URS-L utilization has increased in Japan, the annual complication rate has remained steady. Although URS-L is a useful and less invasive procedure, devastating complications can still occur.


Asunto(s)
Litotripsia por Láser , Complicaciones Posoperatorias , Ureteroscopía , Humanos , Ureteroscopía/efectos adversos , Japón/epidemiología , Masculino , Femenino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Persona de Mediana Edad , Litotripsia por Láser/efectos adversos , Litotripsia por Láser/métodos , Estudios Retrospectivos , Anciano , Adulto , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/etiología , Cálculos Ureterales/cirugía , Cálculos Ureterales/terapia , Obstrucción Ureteral/etiología , Obstrucción Ureteral/epidemiología , Constricción Patológica/etiología , Constricción Patológica/epidemiología , Incidencia , Cálculos Renales/cirugía , Pueblos del Este de Asia
8.
Prostate ; 83(13): 1270-1278, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37316357

RESUMEN

BACKGROUND: The objective of this study was to evaluate the background and treatment course of patients with metastatic prostate cancer (PC), with a particular focus on radiographic progression in the absence of prostate-specific antigen (PSA) progression. METHODS: The study population consisted of 229 patients with metastatic hormone-sensitive PC (HSPC), who received prostate biopsy and androgen deprivation therapy at Kobe University Hospital between January 2008 and June 2022. Clinical characteristics were retrospectively evaluated using medical records. PSA progression-free status was defined as ≤1.05 times greater than that from 3 months before. Multivariate analyses were performed using the Cox proportional hazards regression model to identify parameters associated with time to progression on imaging without PSA elevation. RESULTS: A total of 227 patients with metastatic HSPC without neuroendocrine PC were identified. The median follow-up period was 38.0 months, with a median overall survival of 94.9 months. Six patients exhibited disease progression on imaging without PSA elevation during HSPC treatment, three during first-line castration-resistant PC (CRPC) treatment, and two during late-line CRPC treatment. The rate of disease progression without PSA elevation at 3 years after treatment initiation was 7.4%. Multivariate analysis revealed that organ metastases and upfront treatment with docetaxel or androgen receptor axis-targeted therapy were independent prognostic factors for imaging progression without PSA elevation. CONCLUSIONS: Disease progression on imaging without PSA elevation occurred not only during HSPC treatment and first-line CRPC treatment, but also during late-line CRPC treatment. Patients with visceral metastases or those treated with upfront androgen receptor axis-targeted or docetaxel may be more prone to such progression.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Docetaxel/uso terapéutico , Antígeno Prostático Específico/uso terapéutico , Receptores Androgénicos , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Estudios Retrospectivos , Progresión de la Enfermedad , Resultado del Tratamiento
9.
Prostate ; 83(12): 1217-1226, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37221965

RESUMEN

BACKGROUND: Ultrasound (US) can induce cell injury, and we have previously reported that adjusting the pulse repetition frequency (PRF) of ultrasound output can induce prostate cancer cell destruction without causing a rise in the temperature of the irradiated area. In this study, we examined the mechanism of nonthermal ultrasound cell destruction, which was not fully clarified in our previous reports. METHODS: In vitro, we evaluated postirradiation cells immediately after treatment and examined membrane disruption by proliferation assay, LDH assay, and apoptosis assay. In vivo, we injected mice with human LNCaP and PC-3 prostate cancer cells and evaluated the therapeutic effects of US irradiation by H-E staining and immunostaining. RESULTS: Proliferation assays showed inhibition at 3 h postirradiation independently of PRF and cell line (p < 0.05). Quantitative assessment of apoptosis/necrosis by flow cytometry showed widely varying results depending on cell type. LNCaP showed an increase in late apoptosis at 0 h independent of PRF (p < 0.05), while PC-3 showed no significant difference at 0 h. The LDH assay showed an increase in LDH independent of PRF in LNCaP (p < 0.05 respectively), but no significant difference in PC-3. In vivo, tumor volume was compared and a significant reduction was observed at 10 Hz for LNCaP (p < 0.05) and 100 Hz for PC-3 (p < 0.001) at 3 weeks after the start of irradiation. The excised tumors were evaluated with Ki-67, Caspase-3, and CD-31 and showed a significant treatment effect independent of cell type and PRF (p < 0.001 respectively). CONCLUSION: Examining the mechanism behind the therapeutic effect of US irradiation revealed that the main effect was achieved by apoptosis induction rather than necrosis.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Animales , Ratones , Ratones Desnudos , Neoplasias de la Próstata/metabolismo , Próstata/patología , Apoptosis , Modelos Animales de Enfermedad , Necrosis , Línea Celular Tumoral
10.
Cancer Immunol Immunother ; 72(6): 1903-1915, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36729213

RESUMEN

BACKGROUND: Anti-PD-1 antibodies are widely used for cancer treatment including advanced renal cell carcinoma (RCC). However, their therapeutic and adverse effects vary among patients. This study aimed to identify genetic markers that predict outcome after nivolumab anti-PD-1 antibody treatment for advanced RCC. METHODS: This study was registered on the website of the University Hospital Medical Information Network (protocol ID, UMIN000037739). Patient enrollment was conducted at 23 institutions in Japan between August 19, 2019, and September 30, 2020. Patient follow-up ended on March 31, 2021. Patients were treated with nivolumab for advanced clear cell RCC. A genome-wide association study was performed in the development set, while genotyping of target regions in the validation set was undertaken. Single nucleotide polymorphisms (SNPs) in genes of interest CD274, PDCD1LG2 and PDCD1 were genotyped in the combined set. The primary endpoint was the association of SNPs with objective response following nivolumab treatment. As secondary endpoints, the associations of SNPs with radiographic progression-free survival (rPFS) and treatment-related grade ≥ 3 adverse events (AEs) were evaluated. RESULTS: A genome-wide association study followed by a validation study identified that SNPs in FARP1 (rs643896 and rs685736) were associated with objective response and rPFS but not AEs following nivolumab treatment. Furthermore, SNPs in PDCD1LG2 (rs822339 and rs1411262) were associated with objective response, rPFS, and AEs following nivolumab treatment. Genetic risk category determined according to the number of risk alleles in SNPs (rs643896 in FARP1 and rs4527932 in PDCD1LG2) excellently predicted objective response and rPFS in nivolumab treatment. CONCLUSION: This study revealed that SNPs in FARP1 and PDCD1LG2 were correlated with outcome in nivolumab treatment. The use of these SNPs may be beneficial in selecting appropriate treatment for individual patients and may contribute to personalized medicine.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Nivolumab/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Estudio de Asociación del Genoma Completo , Supervivencia sin Progresión , Polimorfismo de Nucleótido Simple , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética
11.
Genes Cells ; 27(10): 602-612, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36054428

RESUMEN

Bladder cancer (BlC) is the fourth most common cancer in males worldwide, but few systemic chemotherapy options for its effective treatment exist. The development of new molecularly-targeted agents against BlC is therefore an urgent issue. The Hippo signaling pathway, with its upstream LATS kinases and downstream transcriptional co-activators YAP1 and TAZ, plays a pivotal role in diverse cell functions, including cell proliferation. Recent studies have shown that overexpression of YAP1 occurs in advanced BlCs and is associated with poor patient prognosis. Accessing data from our previous screening of a chemical library of compounds targeting the Hippo pathway, we identified DMPCA (N-(3,4-dimethoxyphenethyl)-6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-amine) as an agent able to induce the phosphorylation of LATS1 and YAP1/TAZ in BlC cells, thereby suppressing their viability both in vitro and in mouse xenografts. Our data indicate that DMPCA has a potent anti-tumor effect, and raise the possibility that this agent may represent a new and effective therapeutic option for BlC.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Animales , Humanos , Masculino , Ratones , Aciltransferasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Aminas , Carbazoles , Proteínas Serina-Treonina Quinasas , Transducción de Señal/fisiología , Factores de Transcripción/metabolismo , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Proteínas Señalizadoras YAP
12.
Oncology ; 101(10): 645-654, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37364538

RESUMEN

INTRODUCTION: Prostate cancer (PCA) is one of the most common cancers in the world, and current therapies are debilitating to patients. To develop a novel modality for the treatment of PCA, we evaluated the efficacy of intralesional administration of the Sirt3 activator Honokiol (HK) and the NADPH oxidase inhibitor Dibenzolium (DIB). METHODS: We used a well-established transgenic adenocarcinoma mouse prostate (TRAMP-C2) model of hormone-independent PCA. MTS assay, apoptosis assay, wound healing assay, transwell invasion assay, RT-qPCR, and Western blotting were conducted in vitro, and HK and DIB were intratumorally administered to mice bearing TRAMP-C2 tumors. Tumor size and weight were observed over time. After removing tumors, H-E staining and immunohistochemistry (IHC) staining were conducted. RESULTS: Treatment by HK or DIB showed an inhibitory effect on cell proliferation and migration in PCA cells. Poor ability to induce apoptosis in vitro, insufficient expression of caspase-3 on IHC staining, and increased necrotic areas on H-E staining indicated that necrosis plays an important role in cell death in treating groups by HK or DIB. RT-PCR, Western blotting, and IHC staining for epithelial mesenchymal transition (EMT) markers suggested that EMT was suppressed by HK and DIB individually. In addition, HK induced activation of CD3. Mouse experiments showed safe antitumor effects in vivo. CONCLUSIONS: HK and DIB suppressed PCA proliferation and migration. Further research will explore the effects of HK and DIB at the molecular level to reveal new mechanisms that can be exploited as therapeutic modalities.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Ratones , Animales , Línea Celular Tumoral , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Inmunohistoquímica , Transición Epitelial-Mesenquimal , Proliferación Celular , Movimiento Celular
13.
World J Urol ; 41(4): 1181-1186, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36929408

RESUMEN

PURPOSE: Non-absorbable clips are widely used in urologic surgery and they may come in contact with an open urinary tract intraoperatively. As a result, stray clips in the urinary tract and associated intractable infections have been reported. We developed a bioabsorbable metal and evaluated whether it would dissolve if it strayed into the urinary tract. METHODS: We prepared four types of alloys mainly comprising zinc (Zn) with small amounts of magnesium (Mg) and strontium (Sr), and the biological effects, degradability, strength, and ductility were investigated. Each alloy was implanted in the bladder of five rats for 4, 8, and 12 weeks. The alloys were removed and evaluated for degradability, stone adhesion, and tissue changes. The Zn-Mg-Sr alloy had degradability and no stone adhesion in the rat experiments, and it was implanted in the bladders of five pigs for 24 weeks. The Mg and Zn levels in the blood were measured, and staple changes were confirmed by cystoscopy. RESULTS: Zn-Mg-Sr alloys showed the best degradability of 6.51% at 12 weeks. In pig experiments, the degradation rate was 3.72% at 24 weeks. None of the pigs had changes in the Zn or Mg concentrations in the blood. Overall, the bladder incision was healed and the gross pathology showed wound healing. CONCLUSIONS: The Zn-Mg-Sr alloys were safely used in animal experiments. Furthermore, the alloys are easy to process and can be formed into various shapes, such as staples, making them useful in robotic surgery.


Asunto(s)
Implantes Absorbibles , Aleaciones , Ratas , Animales , Porcinos , Zinc , Magnesio , Estroncio
14.
Jpn J Clin Oncol ; 53(6): 522-529, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36828781

RESUMEN

OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.


Asunto(s)
Neoplasias Pulmonares , Neoplasias de la Próstata , Carcinoma Pulmonar de Células Pequeñas , Masculino , Humanos , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Carboplatino , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/patología , Resultado del Tratamiento , Neoplasias de la Próstata/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
15.
J Infect Chemother ; 29(12): 1132-1136, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37611743

RESUMEN

INTRODUCTION: Retrograde pyelography (RP) is performed for examination of upper urinary tract cancers and hydronephrosis. Although urinary tract infections (UTI) are known to be complicated by the examination, there are few reports on the frequency of occurrence and prophylactic antibiotics. METHODS: The incidence of UTI and febrile UTI (f-UTI) and patient background information were compared in 388 patients who underwent RP at our hospital from January 2018 to December 2022. We also examined the administration of pre-RP antibiotics. RESULTS: Of the 388 patients who underwent RP, 27 (6.9%) had UTI and 17 (4.4%) had f-UTI. Of the 27 UTI cases, 25 (92.6%) were pyelonephritis; 20 (74.0%) were hospitalized and 2 (7.4%) presented with septic shock and were managed in the intensive care unit. When comparing the background of patients with UTI, no significant differences were found in the present study, but when limited to the 17 cases of f-UTI, the presence of hydronephrosis before RP and not prescribing antibiotics before RP were associated with significantly higher incidence of f-UTI (p = 0.019, p = 0.036, respectively). Especially for patients without pyuria and bacteriuria before RP, prescribing antibiotics before RP resulted in 0 cases of f-UTI (p = 0.020). CONCLUSION: This retrospective study showed that the presence of hydronephrosis before RP and not prescribing prophylactic antibiotics before RP are risk factors for f-UTI.

16.
Lett Appl Microbiol ; 76(2)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36763780

RESUMEN

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a life-threatening pathogen that has not been fully investigated on a molecular basis. Therefore, the molecular mechanisms of carbapenem resistance in CRKP collected from medical institutions in Hyogo Prefecture has been analyzed. Antimicrobial susceptibilities and the presence of carbapenemase along with epidemiological analyzes using multilocus sequence typing (MLST) have been investigated. The relative expression of efflux pump genes and mutations of ompK35 and ompK36, encoding the outer membrane porin, were also assessed for their relationship with carbapenem resistance. Most of the collected 22 CRKP isolates were non-susceptible to imipenem (68.2%), meropenem (90.9%), and ertapenem (81.8%), but all 22 strains were susceptible to colistin. Twelve strains (54.5%) were detected for carbapenemase genes such as blaIMP-6. Sequence type 37 was detected by MLST in 10 strains (45.5%). Non-carbapenemase-producing strains had high resistance rates for three carbapenems, and the main cause of resistance was ompK35 mutation. In conclusion, the main cause of resistance was imipenemase metallo-ß-lactamase (IMP-6) production in carbapenemase-producing strains, and ompK35 mutation in non-carbapenemase-producing strains. Susceptibility to carbapenem did not differ in CRKP regardless of carbapenemase production, except for imipenem susceptibility. This result contributes to a more insightful understanding of the mechanisms of CRKP in Japan.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Humanos , Klebsiella pneumoniae , Antibacterianos/farmacología , Tipificación de Secuencias Multilocus , Proteínas Bacterianas/metabolismo , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Carbapenémicos/farmacología , Imipenem/farmacología , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Porinas/genética , Pruebas de Sensibilidad Microbiana
17.
Urol Int ; 107(3): 321-326, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36731453

RESUMEN

Combination therapies of an immune checkpoint inhibitor and a molecular targeted agent are widely accepted as an appropriate initial systemic therapy for metastatic renal cell carcinoma (RCC), but there is little published evidence regarding the efficacy of this approach in patients with end-stage renal disease (ESRD). Here, we report three patients who were undergoing hemodialysis for ESRD whose metastatic RCC was successfully treated using avelumab plus axitinib. The patients were a 67-year-old man with swollen lymph nodes, a 65-year-old man with pleural dissemination, and a 71-year-old man with lung nodules and an infra-diaphragmatic nodule. They were administered a combination of avelumab plus axitinib as their initial systemic therapy following definitive surgical therapy. The best response of three patients was graded as partial response. No severe adverse events were identified. This is the first report of the use of combination therapy consisting of avelumab plus axitinib in patients with ESRD undergoing hemodialysis. We found that this combination was useful in such patients.


Asunto(s)
Carcinoma de Células Renales , Fallo Renal Crónico , Neoplasias Renales , Masculino , Humanos , Anciano , Axitinib/uso terapéutico , Axitinib/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Estudios Retrospectivos , Diálisis Renal , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia
18.
Int J Urol ; 30(5): 431-436, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36788717

RESUMEN

Prostatitis is classified into four categories according to the National Institutes of Health Consensus Classification. The largest category, Category III chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), has a wide range of symptoms and is difficult to diagnose because diagnosis is based on exclusion. Although many treatment modalities, including both pharmacological and non-pharmacological treatments, have been tried, definitive treatment methods have not yet been established, and many urologists struggle with the daily treatment of these conditions. The reasons for the failure of treatment are not only the wide variety of symptoms, but also the wide variety of causes. Therefore, the UPOINTS system is widely used, in which treatment methods are divided or combined according to symptoms and causes. This article summarizes the reports on treatment and reviews treatment findings for CP/CPPS in accordance with the UPOINTS system.


Asunto(s)
Dolor Crónico , Prostatitis , Masculino , Humanos , Prostatitis/diagnóstico , Prostatitis/terapia , Prostatitis/complicaciones , Enfermedad Crónica , Dolor Pélvico/diagnóstico , Dolor Pélvico/etiología , Dolor Pélvico/terapia , Dolor Crónico/diagnóstico , Dolor Crónico/terapia , Dolor Crónico/complicaciones
19.
Int J Urol ; 30(12): 1175-1179, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37654155

RESUMEN

OBJECTIVES: The aims of the present study were to describe the perioperative findings of the first series of patients undergoing robot-assisted radical nephrectomy (RARN) with a newly launched platform, the hinotori surgical robot system, and compare the findings with a similar set receiving RARN with the existing system, da Vinci. METHODS: This study included 34 patients, consisting of 13 and 21 undergoing RARN using the hinotori and da Vinci robotic systems, respectively. As a rule, RARN was performed via an intraperitoneal approach employing 3 robotic arms, irrespective of the robotic systems. RESULTS: In the hinotori group, the median age, body mass index and tumor diameter were 65 years, 23.3 kg/m2 and 50 mm, respectively. All surgical procedures with hinotori could be completed by a purely robotic approach. In the hinotori group, the median operative time, time using the robotic system, estimated blood loss and length of hospital stay were 157, 83 min, 11 mL and 6 days, respectively, and major perioperative complications did not occur. In this group, 3, 1 and 9 patients were pathologically diagnosed with pT1a, pT1b and pT3a tumors, respectively. No significant differences in baseline characteristics were noted between the hinotori and da Vinci groups, and there were also no significant differences in perioperative findings between them. CONCLUSIONS: Despite a case series with a small sample size, this is the first report evaluating RARN using the hinotori surgical robot system, which could be safely conducted and achieved perioperative outcomes similar to that using the da Vinci system.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Anciano , Masculino , Robótica/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Nefrectomía/efectos adversos , Nefrectomía/métodos , Tiempo de Internación , Prostatectomía/métodos , Resultado del Tratamiento , Estudios Retrospectivos
20.
Int J Urol ; 30(2): 220-225, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36305835

RESUMEN

OBJECTIVE: This study aimed to evaluate the pelvicalyceal anatomy on accessibility of reusable flexible ureteroscopy (fURS) to the lower pole calyx during retrograde intrarenal surgery (RIRS). METHODS: Here, 854 patients with ureteral or kidney stones with access to a renal collecting system using reusable fURS were classified into either the accessible group, in whom the deepest lower pole calyces could be touched; and the inaccessible group, in whom the deepest lower calyces could not be touched. We measured the infundibulopelvic angle (IPA), infundibular width (IW), infundibular length (IL), and calyceal pelvic height (CPH) using retrograde pyelograms and performed intergroup comparisons. RESULTS: The median IPA, IW, IL, and CPH in the accessible and inaccessible group were 60.5° and 45.6° (p < 0.001), 10.8 and 9.4 mm (p < 0.001), 33.2 and 36.4 mm (p < 0.001), and 25.9 and 30.9 mm (p < 0.001), respectively. IPA (OR 0.963, 95% CI 0.952-0.974, p < 0.001) and IW (OR 0.519, 95% CI 0.331-0.816, p = 0.004) were significant risk factors of renal pelvicalyceal anatomy related to the accessibility of the lower pole calyces. The cut-off value for IPA and IW was 45.8°(p < 0.001) and 7.8 mm (p < 0.001), respectively. CONCLUSIONS: IPA < 45.8° and IW <7.8 mm were negative predictors to access the lower pole calyces when using reusable fURS during RIRS.


Asunto(s)
Cálculos Renales , Uréter , Humanos , Ureteroscopía , Riñón/diagnóstico por imagen , Riñón/cirugía , Cálices Renales/cirugía , Cálices Renales/anatomía & histología , Cálculos Renales/cirugía , Uréter/cirugía , Resultado del Tratamiento
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