RESUMEN
The HECT-type ubiquitin E3 ligases including ITCH regulate many aspects of cellular function through ubiquitinating various substrates. These ligases are known to be allosterically autoinhibited and to require an activator protein to fully achieve the ubiquitination of their substrates. Here we demonstrate that FAM189A2, a downregulated gene in breast cancer, encodes a new type of ITCH activator. FAM189A2 is a transmembrane protein harboring PPxY motifs, and the motifs mediate its association with and ubiquitination by ITCH. FAM189A2 also associates with Epsin and accumulates in early and late endosomes along with ITCH. Intriguingly, FAM189A2 facilitates the association of a chemokine receptor CXCR4 with ITCH and enhances ITCH-mediated ubiquitination of CXCR4. FAM189A2-knockout prohibits CXCL12-induced endocytosis of CXCR4, thereby enhancing the effects of CXCL12 on the chemotaxis and mammosphere formation of breast cancer cells. In comparison to other activators or adaptors known in the previous studies, FAM189A2 is a unique activator for ITCH to desensitize CXCR4 activity, and we here propose that FAM189A2 be renamed as ENdosomal TRansmembrane binding with EPsin (ENTREP).
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Neoplasias de la Mama , Proteínas Represoras , Ubiquitina-Proteína Ligasas , Neoplasias de la Mama/genética , Quimiocina CXCL12 , Femenino , Técnicas de Inactivación de Genes , Humanos , Receptores CXCR4 , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
Background and Objective: The benefits of physical rehabilitation for very-low-birth-weight infants (VLBWI) have been reported in previous studies; however, the implementation rate of physical rehabilitation in this population remains to be clarified. This study aimed to examine the implementation rate of physical rehabilitation among VLBWI admitted to the neonatal intensive care unit (NICU) using real-world data. Material and Methods: This observational study obtained data from a nationwide administrative database associated with the diagnostic procedure combination (DPC) system in Japan (2014-2019). The participants were 30,464 infants admitted to the NICU between 2014 and 2019. The overall NICU physical rehabilitation rates and background factors of the participants were examined. Results: The overall physical rehabilitation rate in NICUs was 18%. Infants born at <28 weeks of age and extremely low birth weight infants (ELBWI) were more likely to receive physical rehabilitation interventions. The length of stay at the NICU and hospital, as well as the rate of discharge, were higher in patients who received physical rehabilitation than those in infants who did not. Conclusions: One-fifth of all patients admitted to the NICU received physical rehabilitation interventions. Extremely preterm infants and ELBWI were more likely to receive physical rehabilitation interventions. We need to consider ways to increase physical rehabilitation intervention rates in the NICU.
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Unidades de Cuidado Intensivo Neonatal , Humanos , Japón , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Recién Nacido , Estudios Retrospectivos , Femenino , Masculino , Recién Nacido de muy Bajo Peso , Tiempo de Internación/estadística & datos numéricosRESUMEN
Patients with advanced/recurrent mucoepidermoid carcinoma (MEC) have a poor prognosis. This study aimed to establish and characterize human mucoepidermoid carcinoma cell lines from the initial surgical specimen and biopsy specimen upon recurrence from the same patient to provide a resource for MEC research. MEC specimens from the initial surgical procedure and biopsy upon recurrence were used to establish cell lines. The established cell lines were cytogenetically characterized using multi-color fluorescence in situ hybridization and detection, and the sequence of the CRTC1-MAML2 chimeric gene was determined. Furthermore, the susceptibility of head and neck mucoepidermoid carcinoma to standard treatment drugs such as cisplatin, 5-fluorouracil, and cetuximab was investigated. We successfully established unique MEC cell lines, AMU-MEC1, from an initial surgical specimen and AMU-MEC1-R1 and AMU-MEC1-R2 from the recurrent biopsy specimen in the same patient. These cell lines exhibited epithelial morphology and developed in vitro-like cobblestones. They shared eight chromosomal abnormalities, including der(19)ins(19;11)(p13;?), which resulted in a chimeric CRTC1-MAML2 gene, indicating the same origin of the cell lines. The susceptibility of all cell lines to cisplatin and 5-fluorouracil was low. Interestingly, EGFR dependency for cell growth decreased in AMU-MEC-R1 and AMU-MEC-R2 but was retained in AMU-MEC1. These cytogenetic and biochemical findings suggest that the established cell lines can be used to investigate the disease progression mechanisms and develop novel therapeutics for MEC.
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Carcinoma Mucoepidermoide , Neoplasias de las Glándulas Salivales , Humanos , Proteínas de Unión al ADN/genética , Transactivadores/genética , Carcinoma Mucoepidermoide/patología , Hibridación Fluorescente in Situ , Cisplatino , Factores de Transcripción/genética , Biopsia , Línea Celular Tumoral , Fluorouracilo/farmacología , Neoplasias de las Glándulas Salivales/patología , Proteínas de Fusión Oncogénica/genéticaRESUMEN
BACKGROUND: Calcified amorphous tumor (CAT) of the heart is a rare non-neoplastic intracardiac mass, a calcium deposition surrounded by amorphous fibrous tissue, and possibly causes cerebral embolism. Even rarer is CAT associated with infection, and no CAT with antecedent infection has been reported to our knowledge. In addition, although some CAT in patients on hemodialysis has been reported to grow rapidly, no case has been reported on CAT that grew and diminished rapidly in a short period of time. Here, we report the case of an 82-year-old Japanese woman with normal renal function who developed multiple cerebral infarctions due to CAT that grew rapidly, associated with inflammation from an antecedent infection, and diminished rapidly by detachment of fibrin on the mass surface and antithrombotic drugs. CASE PRESENTATION: The patient developed fever after dental treatment and found musical hallucination on the left ear worsened in degree and frequency. In a nearby clinic, she was treated with antibiotics, and her body temperature turned to normal in approximately 1 month. She presented to our hospital for workup on the worsened musical hallucination. Magnetic resonance imaging (MRI) showed multiple cerebral infarctions, and transthoracic echocardiography (TTE) revealed an immobile hyperechoic mass with an acoustic shadow arising from a posterior cusp of the mitral valve. CAT was suspected and treated with apixaban and aspirin. Follow-up MRI and TTE showed newly developed multiple cerebral infarctions and rapidly diminished CAT. Cardiac surgery was performed to resect the CAT. The pathological findings showed calcifications surrounded by amorphous fibrous tissue including fibrin, indicating CAT. The patient's symptoms improved and no cerebral infarctions recurred in 4 months follow-up. CONCLUSION: Inflammation from an antecedent infection can cause CAT to grow rapidly. Fibrous tissue including fibrin may attach to the surface of CAT, resulting in multiple cerebral infarctions. Fibrous tissue may detach and disappear by antithrombotic drugs, leading to a rapid diminishment of CAT in size.
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Calcinosis , Neoplasias Cardíacas , Femenino , Humanos , Fibrinolíticos , Neoplasias Cardíacas/patología , Fibrina , Calcio , Recurrencia Local de Neoplasia , Calcinosis/complicaciones , Infarto Cerebral/complicaciones , Infarto Cerebral/diagnóstico por imagen , Aspirina , Inflamación/complicaciones , Alucinaciones/complicaciones , AntibacterianosRESUMEN
OBJECTIVE: Radical cystectomy remains the standard treatment for muscle-invasive bladder cancer; however, a substantial number of patients with muscle-invasive bladder cancer are not appropriate candidates to radical cystectomy due to co-morbidities or anxiety regarding bladder preservation. Trimodal bladder-sparing therapy is an intelligent and attractive treatment option for such patients. We established a novel treatment strategy using trimodal treatment with gemcitabine and cisplatin. METHODS: Patients diagnosed with muscle-invasive bladder cancer by transurethral resection of bladder tumor and who wished for bladder preservation were recruited. The regimens were gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 in day 1 and concomitant irradiation 1.8 Gy/Fr, five fractions per week. Irradiation was administered to the true pelvis up to 36 Gy and was then boosted to the entire bladder until a total of 54 Gy. Transurethral resection of bladder tumor was also performed after chemoradiotherapy to evaluate pathological response to treatment. We evaluated treatment efficacy and survival, safety of chemoradiotherapy with gemcitabine and cisplatin. RESULTS: Thirty-eight patients were enrolled, and three patients were excluded. Pathological complete response after chemoradiotherapy was observed in 31 patients, and the 5-year bladder-intact metastasis-free survival rate was 76%. The 5-year cancer-specific and overall survival rates for chemoradiotherapy were 85 and 75%, respectively, which were not significantly different from those for radical cystectomy (73 and 71%, respectively). Grade 3/4 adverse events included neutropenia (63%), anemia (18%) and thrombocytopenia (37%); however, treatment-related deaths were not observed. CONCLUSIONS: Chemoradiotherapy using gemcitabine and cisplatin for muscle-invasive bladder cancer is effective for local cancer control and shows no significant difference in oncological prognosis compared with radical cystectomy.
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Neoplasias de la Vejiga Urinaria , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia/efectos adversos , Cisplatino , Terapia Combinada , Cistectomía , Desoxicitidina/análogos & derivados , Humanos , Músculos/patología , Invasividad Neoplásica , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , GemcitabinaRESUMEN
The expression of programmed death ligand-1 (PD-L1) is controlled by complex mechanisms. The elucidation of the molecular mechanisms of PD-L1 expression is important for the exploration of new insights into PD-1 blockade therapy. Detailed mechanisms of the in situ expression of PD-L1 in tissues of oral squamous cell carcinomas (OSCCs) have not yet been clarified. We examined the mechanisms of PD-L1 expression focusing on the phosphorylation of downstream molecules of epidermal growth factor (EGF) and interferon gamma (IFN-γ) signaling in vitro and in vivo by immunoblotting and multi-fluorescence immunohistochemistry (MF-IHC), respectively. The in vitro experiments demonstrated that PD-L1 expression in OSCC cell lines is upregulated by EGF via the EGF receptor (EGFR)/PI3K/AKT pathway, the EGFR/STAT1 pathway, and the EGFR/MEK/ERK pathway, and by IFN-γ via the JAK2/STAT1 pathway. MF-IHC demonstrated that STAT1 and EGFR phosphorylation was frequently shown in PD-L1-positive cases and STAT1 phosphorylation was correlated with lymphocyte infiltration and EGFR phosphorylation. Moreover, the phosphorylation pattern of the related molecules in PD-L1-positive cells differed among the cases investigated. These findings indicate that PD-L1 expression mechanisms differ depending on the tissue environment and suggest that the examination of the tissue environment and molecular alterations of cancer cells affecting PD-L1 expression make it necessary for each patient to choose the appropriate combination drugs for PD-1 blockade cancer treatment.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Factor de Crecimiento Epidérmico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Interferón gamma/uso terapéutico , Neoplasias de la Boca/metabolismo , Fosfatidilinositol 3-Quinasas , Receptor de Muerte Celular Programada 1 , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
Immunotherapy with immune-checkpoint therapy has recently been used to treat oral squamous cell carcinomas (OSCCs). However, improvements in current immunotherapy are expected because response rates are limited. Transforming growth factor-ß (TGF-ß) creates an immunosuppressive tumor microenvironment (TME) by inducing the production of regulatory T-cells (Tregs) and cancer-associated fibroblasts and inhibiting the function of cytotoxic T-lymphocytes (CTLs) and natural killer cells. TGF-ß may be an important target in the development of novel cancer immunotherapies. In this study, we investigated the suppressive effect of TGF-ß on CTL function in vitro using OSCC cell lines and their specific CTLs. Moreover, TGFB1 mRNA expression and T-cell infiltration in 25 OSCC tissues were examined by in situ hybridization and multifluorescence immunohistochemistry. We found that TGF-ß suppressed the function of antigen-specific CTLs in the priming and effector phases in vitro. Additionally, TGF-ß inhibitor effectively restored the CTL function, and TGFB1 mRNA was primarily expressed in the tumor invasive front. Interestingly, we found a significant negative correlation between TGFB1 mRNA expression and the CD8+ T-cell/Treg ratio and between TGFB1 mRNA expression and the Ki-67 expression in CD8+ T-cells, indicating that TGF-ß also suppressed the function of CTLs in situ. Our findings suggest that the regulation of TGF-ß function restores the immunosuppressive TME to active status and is important for developing new immunotherapeutic strategies, such as a combination of immune-checkpoint inhibitors and TGF-ß inhibitors, for OSCCs.
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Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia Adoptiva/métodos , Neoplasias de la Boca/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Linfocitos T Citotóxicos/efectos de los fármacos , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Microambiente Tumoral/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Fibroblastos Asociados al Cáncer/citología , Fibroblastos Asociados al Cáncer/inmunología , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Interferón gamma/análisis , Interferón gamma/metabolismo , Antígeno Ki-67/metabolismo , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Linfocitos Infiltrantes de Tumor/citología , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , ARN Mensajero/metabolismo , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Sales de Tetrazolio/farmacología , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/inmunología , Factor de Crecimiento Transformador beta1/análisis , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismo , Adulto JovenRESUMEN
Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers worldwide, with high morbidity and mortality rates. Despite numerous attempts to identify prognostic markers for the CRC patients, the significance of the association of cellular proliferation markers with survival is controversial. Here we used immunohistochemistry to detect four markers of cellular proliferation expressed in primary CRC tissue specimens (n = 269) to assess their potential to serve as prognostic factors. CRC cells variably expressed phospho-histone H3 (PHH3) (range, 0-76 per high-powered field (HPF); median, 7 per HPF), cyclin A (CCNA) (range, 11.3-73.7%; median, 32%), geminin (GMNN) (range, 7.8-82.0%; median, 37.1%), and marker of proliferation Ki-67 (MKI67) (range, 4.9-96.6%; median, 49.6%). Among them, patients with PHH3-high (≥7 per HPF) tumors uniquely experienced significantly longer 5-year survival than those with PHH3-low (≤6 per HPF) (81.8% vs. 65.5%; P = 0.0047). Multivariable Cox hazards regression analysis identified PHH3-high (hazard ratio, 0.54; 95% confidence interval, 0.31-0.92; P = 0.025) as potential favorable factors. PHH3 levels inversely associated with pT stage (P < 0.0001) and were significantly and inversely associated with tumor diameter (ρ = -0.314, P < 0.0001). These findings support the use of PHH3 immunohistochemistry for predicting the prognoses of patients with CRC.
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Biomarcadores de Tumor/análisis , Neoplasias Colorrectales , Anciano , Anciano de 80 o más Años , Proliferación Celular , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Femenino , Histonas/análisis , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Despite the confirmed anti-cancer effects of T-cell immune checkpoint inhibitors, in colorectal cancer (CRC) they are only effective in a small subset of patients with microsatellite-unstable tumors. Thus, therapeutics targeting other types of CRCs or tumors refractory to T-cell checkpoint inhibitors are desired. The binding of aberrantly expressed CD47 on tumor cells to signal regulatory protein-alpha (SIRPA) on macrophages allows tumor cells to evade immune destruction. Based on these observations, drugs targeting the macrophage checkpoint have been developed with the expectation of anti-cancer effects against T-cell immune checkpoint inhibitor-refractory tumors. In the present study, 269 primary CRCs were evaluated immunohistochemically for CD47, SIRPA, CD68, and CD163 expression to assess their predictive utility and the applicability of CD47-SIRPA axis-modulating drugs. Thirty-five percent of the lesions (95/269) displayed CD47 expression on the cytomembrane of CRC cells. CRCs contained various numbers of tumor-associated immune cells (TAIs) with SIRPA, CD68, or CD163 expression. The log-rank test revealed that patients with CD47-positive CRCs had significantly worse survival than CD47-negative patients. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio (R) = 0.23), age < 70 years (HR = 0.48), and high SIRPA-positive TAI counts (HR = 0.55) as potential favorable factors. High tumor CD47 expression (HR = 1.75), lymph node metastasis (HR = 2.26), and peritoneal metastasis (HR = 5.80) were cited as potential independent risk factors. Based on our observations, CD47-SIRPA pathway-modulating therapies may be effective in patients with CRC.
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Antígenos de Diferenciación/metabolismo , Antígeno CD47/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Receptores Inmunológicos/metabolismo , Anciano , Anciano de 80 o más Años , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Persona de Mediana Edad , Pronóstico , Receptores de Superficie Celular/metabolismo , Análisis de SupervivenciaRESUMEN
OBJECTIVES: To evaluate the impact of smoking and the benefit of smoking cessation on lower urinary tract function and prostatic inflammation in patients with benign prostatic hyperplasia. METHODS: The medical records of 118 benign prostatic hyperplasia patients who underwent transurethral prostatic surgery between 2006 and 2016 were analyzed. Their smoking history was confirmed. The relationship between smoking and main clinical parameters, International Prostate Symptom Scores, uroflowmetry, pressure flow study, magnitude of prostatic inflammation and the level of serum C-reactive protein was investigated. Furthermore, the relationships between smoking cessation and these clinical parameters were assessed. RESULTS: The International Prostate Symptom Scores for straining among the non-smokers were significantly lower than those of the smokers (1.71 vs 2.60, P = 0.029). In the pressure flow study, there were negative correlations between the duration of smoking and strong desire to void (correlation coefficient -0.314, P = 0.013), urgency (correlation coefficient -0.349, P = 0.008) and bladder volume at initial detrusor overactivity (correlation coefficient -0.417, P = 0.021). The duration of smoking cessation was negatively correlated with the magnitude of chronic prostatic inflammation (correlation coefficient -0.253, P = 0.027). In the pressure flow study, the duration of smoking cessation was positively correlated with urgency (correlation coefficient 0.286, P = 0.030) and maximum cystometric capacity (correlation coefficient 0.241, P = 0.050). CONCLUSIONS: Smoking could be a risk factor for the exacerbation of storage dysfunction in benign prostatic hyperplasia patients. Smoking cessation is effective in improving chronic prostatic inflammation and storage dysfunction.
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Hiperplasia Prostática , Prostatitis , Cese del Hábito de Fumar , Humanos , Inflamación/etiología , Masculino , Hiperplasia Prostática/complicaciones , UrodinámicaRESUMEN
AIMS: We evaluated the relationship between body mass index (BMI), including low BMI, and nocturia in Japanese women. METHODS: We collected data on 18 952 women who participated in a multiphasic health screening in Fukui, Japan, in 2006. The participants were asked to report any current or previous disease. Self-reported current body weight and height were used to calculate the BMI. We analyzed the relationship between nocturia, as assessed by a questionnaire, and other variables including age, BMI, and comorbidities. RESULTS: The participants' mean age was 60.6 years. Overall, the prevalence of nocturia (two or more voids/night) was 4.3% and increased in an age-dependent manner. BMI did not affect nocturia in the young participants. The prevalence of nocturia was higher in the high-BMI women (>25.0 kg/m 2 ) in their fifth and sixth decades, but the prevalence was higher in the low-BMI (<18.5 kg/m 2 ) in the women more than 80-years old. A multivariate analysis revealed a significant association between nocturia and the following: age, BMI, sleep disturbance, arteriosclerosis, cerebrovascular disease, chronic pulmonary disease, diabetes mellitus, and hypertension. Not only high BMI (which is already reported as a risk of nocturia) but also low BMI was a factor related to nocturia. CONCLUSION: Our findings indicate that in addition to obesity, low BMI is a factor of nocturia in women.
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Índice de Masa Corporal , Nocturia/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Peso Corporal , Comorbilidad , Femenino , Humanos , Japón/epidemiología , Persona de Mediana Edad , Nocturia/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
AIM: Chronic prostatic inflammation is a critical factor that exacerbates lower urinary tract symptoms (LUTS). The serum C-reactive protein (CRP) level is one of the most common markers with which to assess the degree of inflammation, and it has been reported to be related to the severity of LUTS. However, it is not clear whether the CRP level is linked to the magnitude of prostatic inflammation. We evaluated the relationship between the serum CRP level and the magnitude of prostatic inflammation and assessed the influence of CRP on the severity of LUTS. METHODS: We evaluated the tissue specimens of 121 benign prostatic hyperplasia (BPH) patients who underwent surgery for BPH and preoperative measurement of the serum CRP level. We quantified the magnitude of prostatic inflammation histologically by determining the number of high endothelial venule (HEV)-like vessels and assessed the relationship between the serum CRP level and the HEV-like vessels. We divided the patients into two groups based on the median serum CRP level and compared the clinical parameters of the two groups. RESULTS: The serum CRP level was correlated with the overactive bladder symptom score, whereas it was not correlated with the number of HEV-like vessels. In filling cystometry and pressure-flow study, the proportion of patients with detrusor overactivity in the higher-CRP group was higher than that in the lower-CRP group. CONCLUSIONS: Our present study showed that the serum CRP level was significantly associated with storage dysfunction; in contrast, it was not a surrogate marker of prostatic inflammation.
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Proteína C-Reactiva/análisis , Hiperplasia Prostática/sangre , Prostatitis/sangre , Vejiga Urinaria Hiperactiva/clasificación , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Humanos , Síntomas del Sistema Urinario Inferior/sangre , Síntomas del Sistema Urinario Inferior/complicaciones , Masculino , Persona de Mediana Edad , Resultados Negativos , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/cirugía , Prostatitis/etiología , Estudios Retrospectivos , Vejiga Urinaria Hiperactiva/etiología , UrodinámicaRESUMEN
OBJECTIVES: To evaluate operative and oncological outcomes of laparoscopic adrenalectomy through a transperitoneal approach and retroperitoneal approach for large (>5 cm in diameter) pheochromocytomas. METHODS: We retrospectively compared the results of a transperitoneal approach with those of a retroperitoneal approach in 22 patients (mean age 57.5 years, range 38-76 years) with unilateral large pheochromocytomas (12 right, 10 left). The mean body mass index, operation time, pneumoperitoneum time, estimated blood loss, fluctuation in blood pressure and complication rate were compared between the two approaches. RESULTS: The mean tumor diameter (range) was 7.0 cm (range 5.2-15.5 cm), and no significant differences were observed between the transperitoneal approach and retroperitoneal approach in any baseline clinical parameter. For right-sided procedures, significant differences were found for operation time (113 vs 85 min), pneumoperitoneum time (93 vs 64 min) and estimated blood loss (96 vs 23 mL; P < 0.05, transperitoneal approach and retroperitoneal approach, respectively). No open conversion or recurrence was reported, but one right transperitoneal approach case required blood transfusion. No difference in these parameters was noted on the left side. CONCLUSIONS: For right side procedures, the retroperitoneal approach is feasible, safer and faster than the transperitoneal approach for large pheochromocytomas. Early transection of the feeding artery is beneficial for managing the tumor and reducing the risk of bleeding.
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Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Laparoscopía/métodos , Feocromocitoma/cirugía , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Anciano , Pérdida de Sangre Quirúrgica/prevención & control , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Feocromocitoma/patología , Espacio Retroperitoneal/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Carga TumoralRESUMEN
OBJECTIVES: To elucidate the mechanism of action of the α1 -blocker, naftopidil, in partial bladder outlet obstruction animals, by studying non-voiding contractions, and the levels of mediators were measured with resiniferatoxin treatment. METHODS: A total of 35 female Wistar rats were randomly divided into a sham or bladder outlet obstruction group, and rats in each group were given vehicle or resiniferatoxin. Incomplete urethral ligation was applied to the bladder outlet obstruction group. After cystometry, the intravesical level of prostaglandin E2 and adenosine 5'-triphosphate was measured in the instilled perfusate collected. Naftopidil was given at the time of cystometry. RESULTS: In bladder outlet obstruction rats, non-voiding contractions, bladder capacity, and the intravesical levels of prostaglandin E2 and adenosine 5'-triphosphate were markedly increased compared with sham rats. Naftopidil decreased non-voiding contractions, enlarged the bladder capacity, and decreased the intravesical levels of prostaglandin E2 and adenosine 5'-triphosphate. Resiniferatoxin enhanced non-voiding contractions. The effects of naftopidil on non-voiding contractions and the intravesical level of prostaglandin E2 , but not adenosine 5'-triphosphate, were tolerant to resiniferatoxin. CONCLUSIONS: In bladder outlet obstruction rats, one cause of generation of non-voiding contractions might be bladder wall distension, but not transient receptor potential cation channel V1. The increase in intravesical prostaglandin E2 might also be associated with the generation of non-voiding contractions. Naftopidil inhibits the increase in non-voiding contractions and decreases the intravesical level of prostaglandin E2 , which are independent of transient receptor potential cation channel V1.
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Antagonistas Adrenérgicos alfa/administración & dosificación , Dinoprostona/análisis , Naftalenos/administración & dosificación , Piperazinas/administración & dosificación , Obstrucción del Cuello de la Vejiga Urinaria/tratamiento farmacológico , Vejiga Urinaria/efectos de los fármacos , Animales , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Diterpenos/administración & dosificación , Femenino , Humanos , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Hiperplasia Prostática/complicaciones , Ratas , Ratas Wistar , Canales Catiónicos TRPV/agonistas , Canales Catiónicos TRPV/análisis , Canales Catiónicos TRPV/metabolismo , Vejiga Urinaria/metabolismo , Vejiga Urinaria/fisiopatología , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , Micción/efectos de los fármacos , Micción/fisiologíaRESUMEN
BACKGROUND: Benign prostatic hyperplasia (BPH) is a common urologic disease in older men. Prostatic inflammation research has focused on the magnitude of inflammation; its location has received little attention. We investigated whether the anatomic location of prostatic inflammation is related to the severity of lower urinary tract symptoms (LUTS), measured subjectively and objectively. METHODS: We retrospectively analyzed hematoxylin+eosin-stained tissue specimens from 179 BPH patients who underwent transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). Chronic prostatic inflammation was assessed by the grade (lymphocyte density), extent (lymphocyte distribution), and location of inflammation. Each inflammation-finding type was evaluated in relation to these clinical parameters: age, prostate volume, prostate-specific antigen (PSA) value, body mass index (BMI), the frequency of acute urinary retention (AUR) episodes, the international prostatic symptom score (IPSS), and urodynamic study results. RESULTS: The magnitude and extent of inflammation were not associated with any clinical parameters. We classified the BPH patients into stromal (n = 72) versus non-stromal (n = 105) groups based on their inflammation's dominant location. The stromal group's prostatic volume was significantly larger than the non-stromal group's (63.8 vs 53.8 mL; P = 0.032). AUR episodes were more significantly frequent in the stromal group (36.1% vs 11.4%; P = 0.006). Between-group differences in storage parameters (ie, maximum cystometric capacity) in the urodynamic study were not significantly different. Voiding parameters differed significantly between the stromal and non-stromal groups: maximum detrusor pressure (maxPdet) (116.8 vs 94.5 cmH2 O, P = 0.014), Pdet at the maximum flow rate (Qmax) (95.8 vs 75.4 cmH2 O, P = 0.014), and the bladder outlet obstruction index (BOOI) (78.5 vs 56.3, P = 0.014). The stromal group's Qmax was significantly lower than the non-stromal group's (7.3 vs 9.8 mL/s, P = 0.004). CONCLUSIONS: The location of inflammation in the prostate might be an important factor affecting the severity of LUTS, especially voiding dysfunction.
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Inflamación/patología , Síntomas del Sistema Urinario Inferior/patología , Próstata/patología , Hiperplasia Prostática/patología , Obstrucción del Cuello de la Vejiga Urinaria/patología , Anciano , Anciano de 80 o más Años , Humanos , Inflamación/etiología , Inflamación/fisiopatología , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Próstata/fisiopatología , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/fisiopatología , Estudios Retrospectivos , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , UrodinámicaRESUMEN
AIMS: There are some reports that bladder C-fibers are partially involved in detrusor overactivity in patients with brain lesions. We investigated the contribution of bladder C-fiber to decreased bladder capacity in rats with cerebral infarction. METHODS: Cerebral infarction was induced under halothane anesthesia by left middle cerebral artery occlusion with 4-0 nylon thread in female Sprague-Dawley rats. Intramural amounts of ATP and prostaglandin E2 , in vivo and in vitro ATP, NGF, and prostaglandin E2 release from the distended bladder urothelium, and changes in mRNA expressions of sensor molecules and receptors were monitored 6 h after the occlusion. Cystometry was performed in rats with or without resiniferatoxin pretreatment. RESULTS: Overexpression of sensor molecule, transient receptor potential vanilloid-type channel 1, acid-sensing ion channel 2, purinergic receptors P2X3 , and M2 /M3 muscarinic receptors was found in the bladder. These changes were accompanied by increases in ATP and NGF release from the urothelium. In contrast, when bladder C-fibers were desensitized by resiniferatoxin, no increase in NGF release from the urothelium was found either in vivo or in vitro. There was no difference in the percentage decrease in bladder capacity between cerebral infarction rats pretreated with resiniferatoxin and cerebral infarction rats without pretreatment. CONCLUSIONS: Results indicate that expression of sensor molecules in the bladder is altered by distant infarction in the brain. ATP and NGF release from the urothelium also increased. NGF release was related to activation of bladder C-fibers. Bladder C-fibers might not contribute much to decreased bladder capacity caused by cerebral infarction.
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Infarto Cerebral/metabolismo , Músculo Liso/metabolismo , Fibras Nerviosas Amielínicas/fisiología , Factor de Crecimiento Nervioso/metabolismo , Vejiga Urinaria/inervación , Urotelio/metabolismo , Canales Iónicos Sensibles al Ácido/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Infarto Cerebral/fisiopatología , Femenino , Músculo Liso/fisiopatología , Ratas , Ratas Sprague-Dawley , Receptor Muscarínico M2/metabolismo , Receptor Muscarínico M3/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Vejiga Urinaria/metabolismo , Vejiga Urinaria Hiperactiva/metabolismo , Vejiga Urinaria Hiperactiva/fisiopatología , Urotelio/fisiopatologíaRESUMEN
A 27-year-old Japanese man visited our urological department due to urinary frequency, and we detected a ureterocele by cystoscopy. The treatment consisted of an endoscopic-laser incision of the ureterocele. After the operation, the patient's symptoms subsided, and the vesicoureteral reflux and urinary infection disappeared. With the advances in image diagnostic technology, a ureterocele is easily diagnosed during childhood. In the present case, the ureterocele may have increased in volume over a period of decades, causing the urinary frequency. An endoscopic incision is the standard treatment for ureterocele, but there are concerns about vesicoureteric reflux after the endoscopic-laser incision, the patient is still doing well. The present case indicates that endoscopic-laser incision is an effective treatment for a ureterocele, at least in adult patients.
Asunto(s)
Poliuria/etiología , Ureterocele/cirugía , Adulto , Cistoscopía , Humanos , Masculino , Resultado del Tratamiento , Ureterocele/complicacionesRESUMEN
Ideal therapy for lower urinary tract dysfunction in patients with spinal cord injury (SCI) should decrease detrusor overactivity, thereby promoting urine storage at low intravesical pressure and promoting efficient voiding at low pressure by decreasing detrusor-sphincter dyssynergia. Here we investigated blockade of various α-adrenoceptors to determine the subtype that was principally responsible for improving the voiding dysfunction. The effects of the intravenous α-blocker naftopidil, the α-blocker BMY 7378, and the α-blocker silodosin were evaluated using cystometrography and external urethral sphincter-electromyography (EMG) in decerebrated, unanesthetized female Sprague-Dawley rats with chronic SCI following transection at Th8. Parameters measured included the voided volume, residual volume, voiding efficiency, and burst and silent periods on EMG. Compared with values in decerebrated non-SCI rats, EMG of decerebrated SCI rats revealed more prominent tonic activity, significantly shorter periods of bursting activity, and a reduced ratio of the silent to active period during bursting. Compared with the value before drug administration (control), the voiding efficiency was significantly increased by naftopidil (1 and 3 mg/kg) (<0.05 each), and the burst (<0.01 and <0.05, respectively) and silent periods (<0.01 each) on EMG were significantly lengthened. BMY 7378 (1 mg/kg) significantly increased voiding efficiency and lengthened the burst periods (<0.05 each). Silodosin did not affect any parameters. These results suggest that α-blockade reduces the urethral resistance associated with detrusor-sphincter dyssynergia, thus improving voiding efficiency in SCI rats.
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Piperazinas/administración & dosificación , Receptores Adrenérgicos alfa 1/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Uretra/fisiopatología , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Neurogénica/fisiopatología , Antagonistas Adrenérgicos alfa/administración & dosificación , Antagonistas Adrenérgicos alfa/farmacología , Animales , Femenino , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Traumatismos de la Médula Espinal/fisiopatología , Resultado del Tratamiento , Uretra/efectos de los fármacos , Uretra/inervación , Vejiga Urinaria Neurogénica/etiología , Micción/efectos de los fármacos , Trastornos Urinarios/tratamiento farmacológico , Trastornos Urinarios/etiología , Trastornos Urinarios/fisiopatologíaRESUMEN
A 22-year-old man was admitted to our hospital complaining of a left cervical mass. Computed tomography (CT) showed multiple enlarged lymph nodes at the left cervical vein and para-aortic areas. Histological examination of a biopsy indicated an embryonal carcinoma. The levels of human ß-chorionic gonadotropin (ß-HCG) and lactic dehydrogenase (LDH) were both elevated. Ultrasonography revealed testicular calcification, but there were no findings on magnetic resonance imaging (MRI). The patient was diagnosed as having an extragonadal germ cell tumor. After four courses of chemotherapy with BEP protocol (bleomycin, etoposide and cisplatin), retroperineal lymph node dissection (RPLND) was performed and there was no involvement of the viable cells in the resected lymph nodes. Eight years after chemotherapy, he noticed an enlargement of his left scrotum without pain. ß-HCG was again elevated. A unilateral high orchiectomy was performed, and histology revealed a seminoma. He was staged as pT1N0M0S0. Six months later he remains disease-free.