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Von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80-90% of patients clinically diagnosed with VHL disease. Here, we summarize the results of genetic tests for 206 Japanese VHL families, and elucidate the molecular mechanisms of VHL disease, especially in variant-negative unsolved cases. Of the 206 families, genetic diagnosis was positive in 175 families (85%), including 134 families (65%) diagnosed by exon sequencing (15 novel variants) and 41 (20%) diagnosed by multiplex ligation-dependent probe amplification (MLPA) (one novel variant). The deleterious variants were significantly enriched in VHL disease Type 1. Interestingly, five synonymous or non-synonymous variants within exon 2 caused exon 2 skipping, which is the first report of exon 2 skipping caused by several missense variants. Whole genome and target deep sequencing analysis were performed for 22 unsolved cases with no variant identified and found three cases with VHL mosaicism (variant allele frequency: 2.5-22%), one with mobile element insertion in the VHL promoter region, and two with a pathogenic variant of BAP1 or SDHB. The variants associated with VHL disease are heterogeneous, and for more accuracy of the genetic diagnosis of VHL disease, comprehensive genome and DNA/RNA analyses are required to detect VHL mosaicism, complicated structure variants and other related gene variants.
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Enfermedad de von Hippel-Lindau , Humanos , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/diagnóstico , Japón , Análisis Mutacional de ADN , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Genómica , LinajeRESUMEN
BACKGROUND: Lung cancer is the leading cause of cancer death worldwide, and EGFR mutation is the most common genetic alteration among Asian patients with lung adenocarcinoma. While osimertinib has been shown to be effective in lung cancer patients with EGFR mutation, the majority of patients eventually develop acquired resistance to treatment. We explored the significance of the cyclin D1 expression in patients with EGFR mutation and the potential efficacy of adding abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, simultaneously with osimertinib in vitro. MATERIALS AND METHODS: Immunohistochemical staining, using an anti-cyclin D1 antibody, of specimens from 83 patients with EGFR mutation (male, n = 27; pStage 0-I, n = 71) who were treated by surgical resection between 2017 and 2020, and the relationship between the cyclin D1 expression and clinicopathological factors was analyzed. Additionally, the combined effect of osimertinib and abemaciclib in lung cancer cell lines were analyzed using a growth inhibition test, and the signaling pathway underlying the combined effect was investigated. RESULTS: Cyclin D1 was negative in 18.1% of patients with EGFR mutation, and cyclin D1 negativity was associated with pStage ≥ II (p = 0.02), lymph node metastasis (p = 0.001), and lymphatic invasion (p = 0.01). The cyclin D1-negative group had significantly shorter recurrence-free survival (p = 0.02), although this difference disappeared when limited to pN0 patients. In EGFR mutated cell lines, the combination of osimertinib and abemaciclib demonstrated synergistic effects, which were thought to be mediated by the inhibition of AKT phosphorylation. CONCLUSION: Combination therapy with CDK4/6 inhibitors and EGFR-TKIs may be a promising approach.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Resistencia a Antineoplásicos , Compuestos de Anilina , Receptores ErbB , Quinasas Ciclina-Dependientes , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
The most important issues in the segmentectomy for lung cancer, are the accurate establishment of the suture line and to reduce local recurrence at the resection margin. There are two methods:bronchial dominance as an indicator and intravenous indocyanine green (ICG) as an indicator of blood flow dominance. We have been performing identification by ICG since 2020. After the pulmonary arteriovenous and bronchus are resected, ICG is injected intravenously, and the borders between fluorescent and non-fluorescent area is identified using a ICG thoracoscope, and are resected using an electro-surgical unit or stapler. After that, additional ICG is administered, pulmonary blood flow is checked, and if an uncontaminated area is identified, an additional resection is performed. We have retrospectively reviewed 16 cases of ICG method for lung cancer( all at clinical stageâ ) performed since January 2020, and no recurrence has been observed. We present the details of these cases and report the usefulness of the ICG fluorescence system.
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Verde de Indocianina , Neoplasias Pulmonares , Humanos , Neumonectomía/métodos , Estudios Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , PulmónRESUMEN
5-Aminolevulinic acid is a new-generation photosensitizer with high tumor specificity. It has been used successfully in the diagnosis, treatment, and screening of urological cancers including bladder cancer; specifically, it has been used in photodynamic diagnosis to detect tumors by illuminating the lesion with a specific wavelength of light to produce fluorescence in the lesion after administration of 5-aminolevulinic acid, in photodynamic therapy, which induces tumor cell death via production of cytotoxic reactive oxygen species, and in photodynamic screening, in which porphyrin excretion in the blood and urine is used as a tumor biomarker after administration of 5-aminolevulinic acid. In addition to these applications in urological cancers, 5-aminolevulinic acid-based photodynamic technology is expected to be used as a novel strategy for a large number of cancer types because it is based on a property of cancer cells known as the Warburg effect, which is a basic biological property that is common across all cancers.
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Fotoquimioterapia , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Ácido Aminolevulínico/metabolismo , Ácido Aminolevulínico/uso terapéutico , Biomarcadores de Tumor/metabolismo , Detección Precoz del Cáncer , Humanos , Fármacos Fotosensibilizantes/metabolismo , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Efecto Warburg en OncologíaRESUMEN
Corticotropin-releasing factor (CRF), a representative stress-related neuropeptide, in the central nervous system reportedly both facilitates and suppresses the micturition, therefore, roles of central CRF in regulation of the micturition are still controversial. In this study, we investigated (1) effects of intracerebroventricularly (icv)-administered CRF on the micturition, and (2) brain CRF receptor subtypes (CRFR1/CRFR2) and glutamatergic receptors (NMDA/AMPA subtypes) involved in the CRF-induced effects in male Wistar rats under urethane anesthesia. Intercontraction intervals (ICI), and maximal voiding pressure (MVP), were evaluated by continuous cystometry 45 min before CRF administration or intracerebroventricular pretreatment with other drugs as follows and 3 h after CRF administration. Single-voided volume (Vv), post-voiding residual volume (Rv), bladder capacity (BC), and voiding efficiency (VE) were evaluated by single cystometry 60 min before CRF administration and 60-120 min after the administration. Icv-administered CRF reduced ICI, Vv, and BC without changing MVP, Rv, or VE. The CRF-induced ICI reduction was attenuated by icv-pretreated CP154526 (CRFR1 antagonist), MK-801 (NMDA receptor antagonist), and DNQX (AMPA receptor antagonist), but not by K41498 (CRFR2 antagonist). These results indicate that stimulation of brain CRFR1 can be involved in facilitation of the rat micturition via brain NMDA/AMPA receptors.
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Receptores de Hormona Liberadora de Corticotropina , Micción , Animales , Encéfalo , Hormona Liberadora de Corticotropina/farmacología , Masculino , N-Metilaspartato/farmacología , Ratas , Ratas Wistar , Receptores de N-Metil-D-AspartatoRESUMEN
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.
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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/inmunologíaRESUMEN
Cyclophosphamide (CYP), a broad-spectrum anticancer drug, causes serious side effects, such as haemorrhagic cystitis (HC). Hydrogen sulfide (H2S), an endogenous gasotransmitter, has physiological properties, including anti-inflammation, anti-oxidation, and neuromodulation. In this study, we investigated the effects of NaHS (H2S donor) pretreatment on bladder dysfunction in CYP-treated rats. Male Wistar rats were intraperitoneally pretreated with NaHS (3 or 10 µmol/kg) or vehicle once daily for 7 days before cystometry, and CYP (150 mg/kg) or saline was intraperitoneally administered 2 days before cystometry. After cystometry, the bladder tissues were collected for haematoxylin and eosin staining. In some rats, capsaicin (CAP), which can desensitise CAP-sensitive afferent nerves, was subcutaneously injected at 125 mg/kg 4 days before cystometry. CYP reduced intercontraction intervals (ICI) and bladder compliance (Comp) and increased the number of non-voiding contractions (NVCs) compared with the saline-treated control group. NaHS pretreatment dose-dependently improved the CYP-induced these changes. In bladder tissues, CYP increased histological scores of neutrophil infiltration, haemorrhage, and oedema, while NaHS had no effect on these CYP-induced changes. CAP showed a tendency to suppress CYP-induced changes in ICI. NaHS-induced improvement in CYP-induced changes in urodynamic parameters were not detected in CAP-treated rats. These findings suggest that NaHS pretreatment prevented bladder dysfunction in CYP-treated rats by suppressing CAP-sensitive bladder afferent nerves, but not by suppressing bladder inflammation. Therefore, H2S represents a new candidate as a protective drug for bladder dysfunction induced by HC, a side effect of CYP chemotherapy.
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Cistitis , Sulfuro de Hidrógeno , Animales , Ciclofosfamida/efectos adversos , Cistitis/inducido químicamente , Cistitis/tratamiento farmacológico , Cistitis/prevención & control , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/uso terapéutico , Masculino , Ratas , Ratas Wistar , Vejiga UrinariaRESUMEN
The objective was to evaluate the usefulness of sarcopenia and the neutrophil/lymphocyte ratio (NLR) as therapeutic efficacy predictors in patients who received pembrolizumab after platinum-based chemotherapy for advanced urothelial carcinoma (aUC). Forty-four patients with aUC were enrolled. Patients' background characteristics and clinical factors, the skeletal muscle index, and the psoas muscle index were evaluated. The NLR before and during treatment was calculated, and the rate of change of NLR was calculated. The median age was 70 years; the follow-up period was 13.2 months. The response rate was 54%. The nonresponding group had significantly more sarcopenia cases (P = 0.007) and a high rate of change of NLR (P = 0.0076). Progression-free survival (PFS) was significantly shorter in the group with sarcopenia (P = 0.002). Both PFS and overall survival were significantly shorter with an NLR rate of change greater than or equal to 1 (P = 0.001 and P = 0.002). On multivariate analysis, the presence of immune-related adverse events [hazard ratio (HR), 0.3723; 95% confidence interval (CI), 0.14-0.97; P = 0.04] and the NLR rate of change (HR, 3.986; 95% CI, 1.01-15.70; P = 0.048) were independent predictors of PFS. Sarcopenia and the rate of change of NLR appear to be useful as predictors of pembrolizumab efficacy in aUC.
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Carcinoma de Células Transicionales , Sarcopenia , Neoplasias de la Vejiga Urinaria , Anciano , Anticuerpos Monoclonales Humanizados , Carcinoma de Células Transicionales/tratamiento farmacológico , Femenino , Humanos , Linfocitos/patología , Masculino , Neutrófilos/patología , Pronóstico , Estudios Retrospectivos , Sarcopenia/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
OBJECTIVE: No reports have evaluated the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. The present study aimed to evaluate the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. We therefore divided patients into 2 groups about the age of 70 years and investigated the treatment effects of tadalafil regarding voiding and storage functions by age group. METHODS: Changes from baseline in each parameter (International Prostate Symptom Score [IPSS], quality of life [QOL] score, Overactive Bladder Symptom Score [OABSS], and residual urine volume) at 4, 12, and 24 weeks after initiating tadalafil for benign prostatic hyperplasia (BPH) patients were compared between groups (50-69 years vs. ≥70 years). In addition, side effects of tadalafil were investigated by age group. RESULTS: In the 50-69 years group, significant improvements from baseline were seen in IPSS total and QOL score for all time points. In addition, significant improvements in IPSS storage subscore from baseline were observed at the 4- and 24-week time points. In the ≥70 years group, significant improvements from baseline were seen in IPSS total, IPSS voiding and storage subscores, and QOL score at each time point. CONCLUSIONS: Tadalafil 5 mg once daily appeared effective in clinical settings for elderly BPH patients even over 70 years old.
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Síntomas del Sistema Urinario Inferior , Nocturia , Hiperplasia Prostática , Anciano , Humanos , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Masculino , Nocturia/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/tratamiento farmacológico , Calidad de Vida , Tadalafilo/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the safety and efficacy of CT fluoroscopy-guided percutaneous cryoablation (PCA) after lipiodol marking and embolization (LME) in patients with renal cell carcinoma (RCC). MATERIAL AND METHODS: This study included 29 patients (18 men, 11 women; mean age 69 years, range 22-89 years) with 42 RCCs. They underwent CT fluoroscopy-guided PCA after LME between March 2016 and March 2020. The mean tumor diameter was 21 mm (range 7-50 mm). LME was performed with lipiodol and gelatin particles. PCA was considered successful when the ice ball encapsulated the entire tumor and the margin was sufficient on post-ablation CT scans. RESULTS: LME was successfully performed in 39 of 40 tumors (97.5%). PCA after LME was successful in all 39 of 39 tumors (100%). During the follow-up period (mean 13.9 ± 12.1 months), one of the 39 tumors (2.6%) developed local tumor progression. A significant complication (reversible hypertensive crisis) was encountered in only one of 37 (2.7%) procedures. The mean eGFR was 64.2 ± 26.8 before and 63.3 ± 26.4 after PCA (p = .44). CONCLUSION: LME using iodized oil and gelatin particles to improve visualization of the RCC facilitated tumor localization on unenhanced CT images. PCA after LME might be a safe and effective for treatment in patients with RCC.
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Carcinoma de Células Renales , Criocirugía , Neoplasias Renales , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/cirugía , Criocirugía/métodos , Aceite Etiodizado , Femenino , Gelatina , Humanos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Thermal ablative techniques are used increasingly to treat renal cell carcinoma (RCC). Percutaneous cryoablation of tumors at the upper pole of the kidney may result in pulmonary damage due to the intervening lung parenchyma. We treated two patients with RCC in the upper pole of the kidney by inducing pneumothorax with a pneumoperitoneum needle before proceeding to percutaneous cryoablation. The procedures, performed under computed tomography (CT) fluoroscopy guidance, resulted in complete tumor necrosis. There was no pulmonary damage.
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Carcinoma de Células Renales , Ablación por Catéter , Criocirugía , Neoplasias Renales , Neumotórax , Carcinoma de Células Renales/cirugía , Ablación por Catéter/métodos , Criocirugía/métodos , Humanos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Neumotórax/etiología , Neumotórax/cirugíaRESUMEN
Brain nicotinic acetylcholine receptors (nAChRs) reportedly suppress the micturition, but the mechanisms responsible for this suppression remain unclear. We previously reported that intracerebroventricularly administered (±)-epibatidine (non-selective nAChR agonist) activated the sympatho-adrenomedullary system, which can affect the micturition. Therefore, we investigated (1) whether intracerebroventricularly administered (±)-epibatidine-induced effects on the micturition were dependent on the sympatho-adrenomedullary system, and (2) brain nAChR subtypes involved in the (±)-epibatidine-induced effects in urethane-anesthetized male Wistar rats. Plasma noradrenaline and adrenaline (catecholamines) were measured just before and 5 min after (±)-epibatidine administration. Evaluation of urodynamic parameters, intercontraction intervals (ICI) and maximal voiding pressure (MVP) by cystometry was started 1 h before (±)-epibatidine administration or intracerebroventricular pretreatment with other drugs and continued 1 h after (±)-epibatidine administration. Intracerebroventricularly administered (±)-epibatidine elevated plasma catecholamines and prolonged ICI without affecting MVP, and these changes were suppressed by intracerebroventricularly pretreated mecamylamine (non-selective nAChR antagonist). Acute bilateral adrenalectomy abolished the (±)-epibatidine-induced elevation of plasma catecholamines, but had no effect on the (±)-epibatidine-induced ICI prolongation. The latter was suppressed by intracerebroventricularly pretreated methyllycaconitine (selective α7-nAChR antagonist), SR95531 (GABAA antagonist), and SCH50911 (GABAB antagonist), but not by dihydro-ß-erythroidine (selective α4ß2-nAChR antagonist). Intracerebroventricularly administered PHA568487 (selective α7-nAChR agonist) prolonged ICI without affecting MVP, similar to (±)-epibatidine. These results suggest that stimulation of brain α7-nAChRs suppresses the rat micturition through brain GABAA/GABAB receptors, independently of the sympatho-adrenomedullary outflow modulation.
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Encéfalo/metabolismo , Receptores de GABA/metabolismo , Micción , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Médula Suprarrenal/efectos de los fármacos , Médula Suprarrenal/metabolismo , Adrenalectomía , Animales , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Epinefrina/sangre , Masculino , Contracción Muscular/efectos de los fármacos , Norepinefrina/sangre , Piridinas/farmacología , Ratas Wistar , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismoRESUMEN
BACKGROUND: To enhance the convenience and reduce the cost of prostate cancer (PC) screening, a one-step prostate-specific antigen (PSA) test was evaluated in a large population. The PSA SPOT test kit enables rapid detection of human PSA in serum or plasma at or above a cutoff level of 4 ng/mL to aid in the diagnosis of PC. METHODS: PC screening using the PSA SPOT test was offered to male participants in educational public lectures that we conducted in various cities. Test results were reported to participants at the end of the lectures. Blood samples from 1429 men were evaluated. Two independent observers interpreted the tests at 15 and 30 min. The remaining serum samples were subsequently tested using a conventional quantitative assay. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the test were 79.9, 93.0, 65.4, 96.6, and 91.2%, respectively. The sensitivity and specificity of the test changed with variations in the reading time. Quantitative assessment of the intensity of the band was correlated with the PSA value. CONCLUSIONS: PSA testing using this kit can be easily performed. The low cost and speed of the test make it a useful and convenient tool for primary PC screening.
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Detección Precoz del Cáncer/métodos , Pruebas Hematológicas/métodos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de TiempoRESUMEN
Photodynamic technology using light-sensitive and fluorescent substances has an important role in an accurate diagnosis for a variety of malignancies, including bladder cancer and prostate cancer. Light-sensitive and fluorescent substances accumulate specifically in tumor cells compared to normal tissue, and by light irradiation and excitation at each specific wavelength, tumor lesion, blood flow, lymph node and so on show fluorescence. 5-Aminolevulinic acid (ALA) is converted to protoporphyrin IX (PpIX) into mitochondria. PpIX is excited by blue light, red fluorescence is emitted in the mitochondria. This phenomenon is the mechanism of ALA-mediated photodynamic diagnosis (ALA-PDD). ALA-PDD has made it possible to visualize smaller lesions and flat lesions that were previously difficult to visualize by endoscope using a white-light source. So accurate diagnosis and complete resection become possible during operation. The accumulation of PpIX in the mitochondria also induces direct mitochondrial damage and subsequent cell death by red and green light. This biological reaction is the ALA-mediate photodynamic therapy (ALA-PDT). ALA-PDT has been developed as a modality for minimum invasive cancer treatment that utilizes low-energy light and photosensitizer. Vascular-activated photosensitizer induces rapid tumor ablation by PDT involving direct tumor cell killing as well as damage to the exposed microvasculature. We summarize the clinical outcomes of PDD and PDT for urothelial carcinoma and prostate cancer.
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Carcinoma de Células Transicionales , Fotoquimioterapia , Neoplasias de la Próstata , Ácido Aminolevulínico , Carcinoma de Células Transicionales/tratamiento farmacológico , Humanos , Masculino , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
OBJECTIVES: To investigate whether a response to hydrogen sulfide donors (GYY4137 and sodium hydrosulfide) and the endogenous hydrogen sulfide system (hydrogen sulfide level and expression of cysteine aminotransferase, cystathionine ß-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase) in the spontaneously hypertensive rat bladder differ with age, we compared the responses of hydrogen sulfide donors to micturition and bladder relaxation, and the endogenous hydrogen sulfide system in the bladder of 18-week versus 12-week-old spontaneously hypertensive rats. METHODS: GYY4137 was intravesically administered and cystometry was performed in anesthetized rats. The responses of sodium hydrosulfide were evaluated in carbachol-mediated precontracted bladder strips. Bladder hydrogen sulfide levels and expression levels of each enzyme were investigated using the methylene blue method and Western blotting, respectively. RESULTS: GYY4137 treatment significantly prolonged intercontraction intervals only in 12-week-old rats. Sodium hydrosulfide-induced bladder relaxation was significantly attenuated in the strips of 18-week-old rats compared with that in 12-week-old rats. In the bladder dome, significant increases in hydrogen sulfide levels and in the expression of cystathionine ß-synthase, 3-mercaptopyruvate sulfurtransferase, and cysteine aminotransferase were observed in 18-week-old rats compared with 12-week-old rats. However, cystathionine γ-lyase bands were not detected in bladder tissues of either group. CONCLUSIONS: Bladder relaxation induced by hydrogen sulfide may be attenuated in spontaneously hypertensive rats in an age-dependent manner.
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Sulfuro de Hidrógeno , Animales , Ratas , Ratas Endogámicas SHR , Vejiga Urinaria , MicciónRESUMEN
PURPOSE: To evaluate the effectiveness of the transarterial infusion of iodized oil and gelatin particles for marking before CT-guided percutaneous cryoablation (PCA) in patients with renal cell carcinoma (RCC). MATERIAL AND METHODS: This study included ten patients (seven men, three women; mean age 53 years) with 13 RCCs between July 2016 and September 2017. The transarterial infusion of iodized oil and gelatin particles was considered successful when iodized oil accumulated in the target area on CT. CT value of the tumor before and after marking was measured and two diagnostic radiologists evaluated the visualization scores by using a five-point scale (5 = excellent to 1 = invisible). RESULTS: Preoperative marking was successful in all 13 tumors; the median visualization score was 5 post-lipiodol marking and 4 at the time of PCA. The mean CT density was 597 ± 371 Hounsfield units (HU) just after marking and 437 ± 234 HU at the time of PCA. All 13 CT-guided PCA procedures were successful. There were no significant complications. During follow-up (median 11.5 ± 7.0 months) there were no local recurrences. CONCLUSION: As the transarterial infusion of iodized oil and gelatin particles improved RCC visualization on CT, its delivery before CT-guided PCA may improve its safety and success rate in patients with RCC.
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Carcinoma Hepatocelular , Carcinoma de Células Renales , Criocirugía , Neoplasias Renales , Neoplasias Hepáticas , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Aceite Etiodizado , Femenino , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: We report the first three cases in which the feasibility and safety of the left snuff box radial access in transcatheter arterial embolization (TAE) for unruptured renal angiomyolipoma (AML) were evaluated. MATERIAL AND METHODS: Three patients with unruptured renal AMLs underwent TAE via the left snuff box radial artery. We retrospectively evaluated the characteristics of the AMLs, technical success rate, clinical success rate, and complications. Technical success and clinical success were defined as successful insertions of microballoon catheters selectively via the left distal radial artery into all intended arteries in a treatment session and shrinkage of tumor size as evaluated by CT or MRI after the procedure, respectively. RESULTS: The median size of the renal AMLs was 49 mm. TAE was successfully performed in all cases and all feeding arteries were successfully selected with a microballoon catheter through the left snuff box radial artery. The median amount of the mixture of ethanol and Lipiodol was 1.8 mL. Tumor shrinkage was confirmed in all with a median follow-up period of 6 months. The clinical success rate was 100%. No major complications occurred. CONCLUSION: The left snuff box access in TAE for an unruptured renal AML is safe and feasible.
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Angiomiolipoma , Embolización Terapéutica , Neoplasias Renales , Tabaco sin Humo , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/terapia , Embolización Terapéutica/efectos adversos , Humanos , Neoplasias Renales/terapia , Arteria Radial , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) has been incorporated into the recent international histological classification of renal tumors. However, to date, there are limited studies describing the clinicopathological features of fumarate hydratase (FH)-deficient RCC, including the hereditary (HLRCC) and sporadic forms. Herein, we present a clinicopathological study of seven cases with FH-deficient RCC. The age of patients ranged from 26 to 70 years with mean and median age of 51.7 and 57 years, respectively. The follow-up data of all patients were available. One patient was alive without the disease and five patients were alive with active disease. One patient died of the disease. Family history of RCC, or skin or uterine smooth muscle tumor within second degree of kinship was present in four of seven patients. Metastasis was observed in all tumors. Metastatic sites included bone, lungs, liver, peritoneum, ovaries, tonsils, or lymph nodes. Grossly, the cut surface of the tumor usually showed light brown, brown, or whitish color. Microscopically, the cytoplasm of the tumor cells was predominantly eosinophilic and all tumors displayed various architectural patterns such as papillary, tubular, solid, or microcystic patterns. Furthermore, two tumors demonstrated a tubulocystic pattern. Sarcomatoid change and rhabdoid features were seen in five tumors and two tumors, respectively. Large cytomegaloviral (CMV) inclusion-like eosinophilic nucleoli surrounded by a clear halo were identified in all tumors. All tumors showed negative immunohistochemical reaction for FH protein. False positive results of TFE3 protein were observed in three tumors. Furthermore, a germline mutation of FH gene was identified in one patient with family history of the disease. In conclusion, FH-deficient RCC includes hereditary and sporadic forms. Grossly, this tumor is solitary and occurs unilaterally. Histologically, the tumor is characterized by various patterns such as papillary, tubular, solid, tubulocystic, or microcystic, has eosinophilic cytoplasm and CMV-like high-grade nuclei. FH-deficient RCCs frequently metastasize to other anatomic sites. TFE immunoreactivity may occur in some FH-deficient RCCs, and immunohistochemistry can accurately diagnose these tumors and mutational analysis of FH gene.
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Carcinoma de Células Renales/patología , Fumarato Hidratasa/deficiencia , Neoplasias Renales/patología , Adulto , Anciano , Carcinoma de Células Renales/enzimología , Femenino , Humanos , Neoplasias Renales/enzimología , Leiomiomatosis/patología , Masculino , Persona de Mediana Edad , Síndromes Neoplásicos Hereditarios/patología , Neoplasias Cutáneas/patología , Neoplasias Uterinas/patologíaRESUMEN
PURPOSE: To evaluate the influence of percutaneous cryoablation for renal cell carcinoma on function of the affected kidney. MATERIALS AND METHODS: Between June 2016 and September 2017 at our institution, 12 inoperable patients underwent 15 cryoablation sessions for 17 small renal tumors. Of these, 9 patients who underwent 11 sessions of cryoablation were the focus of this study. For those patients, time-dependent changes in postoperative renal function were investigated by a retrospective review of clinical records. Evaluated were the estimated glomerular filtration rate (eGFR) and scintigraphy using 99m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before and 1 week, 1-2 months, and more than 6 months after cryoablation. RESULTS: Mean baseline eGFR was 76.88 ± 29.82 mL/min/1.73 m2 (mean ± standard deviation; range, 23.4-112.5). Mean eGFR 1 week, 1-2 months, and more than 6 months after cryoablation were 74.56 ± 26.68 mL/min/1.73 m2 (21.0-101.1), 69.5 ± 25.28 mL/min/1.73 m2 (24.1-105.6), and 75.08 ± 26.25 mL/min/1.73 m2 (29.0-107.3), respectively. Changes were statistically insignificant (P = .6044, P = .6699, and P = .9038, respectively). Regarding split renal function, the mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 47.27% ± 6.14 (38.8%-57.0%). Mean contributions of the affected kidney 1 week after, 1-2 months after, and more than 6 months after cryoablation were 44.40% ± 5.37 (38.3%-53.6%), 44.57% ± 6.52 (34.35%-55.0%), and 45.41% ± 7.77 (34.4%-56.5%), respectively. Differences from baseline were significant for the earliest 2 periods (P = .0473 and P = .0334, respectively) but not the later period (P = .2532). CONCLUSIONS: Results suggested that total renal function does not worsen after cryoablation; however, function of the affected kidney worsened after cryoablation but later partially recovered.
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Carcinoma de Células Renales/cirugía , Criocirugía , Tasa de Filtración Glomerular , Neoplasias Renales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/fisiopatología , Criocirugía/efectos adversos , Femenino , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Neoplasias Renales/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Radiofármacos/administración & dosificación , Recuperación de la Función , Estudios Retrospectivos , Tecnecio Tc 99m Mertiatida/administración & dosificación , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga TumoralRESUMEN
Renal cryoablation has become accepted as treatment for small renal tumors as an alternative to surgery. However, parallel with the increase in the use of this therapy, there also has been increases in the number of reports of complications related to renal cryoablation. One potential complication is injury to important non-renal structures adjacent to the ablated renal tumor, such as the colon, duodenum, ureter, psoas muscle and so on. To prevent injury of adjacent organs, separating organs from the tumor is desirable. Over the past 15 years, several techniques have been developed to protect against injury of organs adjacent to renal tumors that are targets of cryoablation. The most commonly used technique for this purpose has been hydrodissection. Others include dissection with gas, balloon dissection and probe traction. To avoid injury of a ureter running near the renal tumor, pyeloperfusion is known to be useful. The rate of cases necessitating avoidance of organ injury by using these techniques is relatively high. In some cases, more than two techniques are combined. In the present review, we provided an overview of techniques currently available to protect against organ injuries, and discussed the advantages and disadvantages of each technique.