RESUMEN
Drug resistance contributes to poor therapeutic response in urothelial carcinoma (UC). Metabolomic analysis suggested metabolic reprogramming in gemcitabine-resistant urothelial carcinoma cells, whereby increased aerobic glycolysis and metabolic stimulation of the pentose phosphate pathway (PPP) promoted pyrimidine biosynthesis to increase the production of the gemcitabine competitor deoxycytidine triphosphate (dCTP) that diminishes its therapeutic effect. Furthermore, we observed that gain-of-function of isocitrate dehydrogenase 2 (IDH2) induced reductive glutamine metabolism to stabilize Hif-1α expression and consequently stimulate aerobic glycolysis and PPP bypass in gemcitabine-resistant UC cells. Interestingly, IDH2-mediated metabolic reprogramming also caused cross resistance to CDDP, by elevating the antioxidant defense via increased NADPH and glutathione production. Downregulation or pharmacological suppression of IDH2 restored chemosensitivity. Since the expression of key metabolic enzymes, such as TIGAR, TKT, and CTPS1, were affected by IDH2-mediated metabolic reprogramming and related to poor prognosis in patients, IDH2 might become a new therapeutic target for restoring chemosensitivity in chemo-resistant urothelial carcinoma.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Gemcitabina , Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Vía de Pentosa Fosfato , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
In this study, a microfluidic-based system utilizing colorimetric loop-mediated isothermal amplification (LAMP) is introduced for the quantitative analysis of nucleic acid targets. This system offers a user-friendly and cost-effective platform for the multiplexed genetic diagnosis of various infectious diseases across multiple samples. It includes time-lapse imaging equipment for capturing images of the microfluidic device during the LAMP assay and a hue-based quantitative analysis software to analyze the LAMP reaction, streamlining diagnostic procedures. An electric pipette was used to simplify the loading of samples and LAMP reagents into the device, allowing easy operation even by untrained individuals. The hue-based analysis software employs efficient image processing and post-processing techniques to calculate DNA amplification curves based on color changes in multiple reaction chambers. This software automates several tasks, such as identifying reaction chamber areas from time-lapse images, quantifying color information within each chamber, correcting baselines of DNA amplification curves, fitting experimental data to theoretical curves, and determining the threshold time for each curve. To validate the developed system, conventional off-chip LAMP assays were conducted with a 25 µL reaction mixture in 0.2 mL polymerase chain reaction (PCR) tubes using a real-time turbidimeter. The results indicated that the threshold time obtained using the colorimetric LAMP assay in the developed system is comparable to that obtained with real-time turbidity measurements in PCR tubes, demonstrating the system's capability for quantitative analysis of target nucleic acids, including those from human herpesviruses.
Asunto(s)
Colorimetría , Dispositivos Laboratorio en un Chip , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Humanos , Colorimetría/métodos , Colorimetría/instrumentación , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/instrumentación , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , ADN Viral/análisis , ADN Viral/genética , Virosis/diagnóstico , Límite de DetecciónRESUMEN
BACKGROUND: Robot-assisted radical prostatectomy (RARP) is a standard treatment for localized prostate cancer. We previously reported that a large amount of pelvic visceral fat and a small working space, as measured by three-dimensional image analysis, were significantly associated with prolonged console time in RARP, and these factors could be alternatives to the more clinically practical body mass index (BMI) and pelvic width (PW), respectively. Herein, we further investigated whether surgical proficiency affected surgical difficulty as measured by console time. METHODS: Medical records of 413 patients who underwent RARP between 2014 and 2020 at our institution were reviewed. Surgeons who had experience with over and under 100 cases were defined as "experienced" and "non-experienced," respectively. Multivariate logistic regression analyses were performed to identify factors that prolonged console time. RESULTS: The median console times for RARP by experienced and non-experienced surgeons were 87.5 and 149.0 min, respectively; a difficult case was defined as one requiring time greater than the median. Among inexperienced surgeons, higher BMI (p < 0.001, odds ratio: 1.89) and smaller PW (p = 0.001, odds ratio: 1.86) were significant factors that increased console time; the complication rate was increased in patients with these factors. However, these factors did not significantly affect the console time or complication rate among experienced surgeons. CONCLUSION: This study demonstrates that experienced surgeons may be able to overcome obesity- and small workspace-related surgical difficulties. The current analysis may provide useful information regarding unpredictable surgical risks and identify suitable cases for novices.
Asunto(s)
Competencia Clínica , Prostatectomía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Prostatectomía/métodos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Anciano , Estudios Retrospectivos , Tempo Operativo , Índice de Masa Corporal , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
PURPOSE: This study aimed to evaluate the usefulness of the LDN-PSA (LacdiNAc-glycosylated-prostate specific antigen) in detecting clinically significant prostate cancer in patients suspected of having clinically significant prostate cancer on multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Patients with prostate specific antigen levels ranging between 3.0 ng/mL and 20 ng/mL and suspicious lesions with PI-RADS (Prostate Imaging-Reporting and Data System) category ≥3 were included prospectively. The LDN-PSA was measured using an automated 2-step Wisteria floribunda agglutinin lectin-anti-prostate specific antigen antibody sandwich immunoassay. RESULTS: Two hundred four patients were included. Clinically significant prostate cancer was detected in 105 patients. On multivariable logistic regression analysis, prostate specific antigen density (OR 1.61, P = .010), LDN-PSAD (OR 1.04, P = .012), highest PI-RADS category (3 vs 4, 5; OR 14.5, P < .0001), and location of the lesion with highest PI-RADS category (transition zone vs peripheral zone) (OR 0.34, P = .009) were significant risk factors for detecting clinically significant prostate cancer. Among the patients with the highest PI-RADS category 3 (n=113), clinically significant prostate cancer was detected in 28 patients. On multivariable logistic regression analysis to predict the detection of clinically significant prostate cancer in patients with the highest PI-RADS category 3, age (OR 1.10, P = .026) and LDN-PSAD (OR 1.07, P < .0001) were risk factors for detecting clinically significant prostate cancer. CONCLUSIONS: LDN-PSAD would be a biomarker for detecting clinically significant prostate cancer in patients with prostate specific antigen levels ≤20 ng/mL and suspicious lesions with PI-RADS category ≥3. The use of LDN-PSAD as an adjunct to the use of prostate specific antigen levels would avoid unnecessary biopsies in patients with the highest PI-RADS category 3. Multi-institutional studies with large population are recommended.
Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Imagen por Resonancia Magnética , Neoplasias de la Próstata/diagnóstico por imagenRESUMEN
BACKGROUND: Collecting system entry in robot-assisted partial nephrectomy may occur even in cases showing a low N factor in the R.E.N.A.L nephrometry score. Therefore, in this study, we focused on the tumor contact surface area with the adjacent renal parenchyma and attempted to construct a novel predictive model for collecting system entry. METHODS: Among 190 patients who underwent robot-assisted partial nephrectomy at our institution from 2015 to 2021, 94 patients with a low N factor (1-2) were analyzed. Contact surface was measured with three-dimensional imaging software and defined as the C factor, classified as C1, < 10 cm [2]; C2, ≥ 10 and < 15 cm [2]; and C3: ≥ 15 cm [2]. Additionally, a modified R factor (mR) was classified as mR1, < 20 mm; mR2, ≥ 20 and < 40 mm; and mR3, ≥ 40 mm. We discussed the factors influencing collecting system entry, including the C factor, and created a novel collecting system entry predictive model. RESULTS: Collecting system entry was observed in 32 patients with a low N factor (34%). The C factor was the only independent predictive factor for collecting system entry in multivariate regression analysis (odds ratio: 4.195, 95% CI: 2.160-8.146, p < 0.0001). Models including the C factor showed better discriminative power than the models without the C factor. CONCLUSIONS: The new predictive model, including the C factor in N1-2 cases, may be beneficial, considering its indication for preoperative ureteral catheter placement in patients undergoing robot-assisted partial nephrectomy.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Nefrectomía , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Estudios Retrospectivos , Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugíaRESUMEN
BACKGROUND: More patients with renal cell carcinoma are now diagnosed with the disease in its early stages. Although patients with pT1a renal cell carcinoma have a good prognosis and low recurrence rate, a few patients still experience recurrence. Herein, we evaluated the clinicopathological risk factors for postoperative recurrence of pT1aN0M0 renal cell carcinoma. METHODS: An renal cell carcinoma survey was conducted by the Japanese Urological Association to register newly diagnosed cases of renal cell carcinoma. A total of 1418 patients diagnosed with pT1aN0M0 renal cell carcinoma who underwent surgery as the primary surgical treatment were included. We analyzed the recurrence-free survival using the Kaplan-Meier method and clinicopathological factors for recurrence using Cox proportional hazards models. RESULTS: Among 1418 patients, 58 (4.1%) had recurrences after a median follow-up of 62.8 months. The median time to recurrence was 31.0 months. Metastases to the lungs and the bone were observed in 20 and 10 cases, respectively. Significant differences in sex, tumor size, Eastern Cooperative Oncology Group performance status, and dialysis history, preoperative hemoglobin levels, C-reactive protein levels and creatinine levels were observed between the recurrence and non-recurrence groups. Multivariate analysis identified male sex, high C-reactive protein level and tumor size ≥3 cm as independent risk factors. The 5-year recurrence-free survival of patients with 0, 1, 2 and 3 risk factors was 99.0, 97.2, 93.1 and 80.7%, respectively. CONCLUSIONS: Male sex, tumor diameter and a high C-reactive protein level were independent recurrence risk factors for pT1a renal cell carcinoma; special attention should be paid to patients with these risk factors during postoperative follow-up.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/patología , Humanos , Japón/epidemiología , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Masculino , Recurrencia Local de Neoplasia/patología , Nefrectomía/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVES: Laparoscopic radical nephrectomy is the standard surgery for localized renal cell carcinoma. Both tumor and patient factors affect the difficulty of laparoscopic radical nephrectomy. Obesity is a major factor influencing technical difficulty in surgical procedures. This study examined preoperative tumor and patient factors affecting the operating time. METHODS: The data of 123 patients who underwent laparoscopic radical nephrectomy at our institution between January 2014 and December 2018 were retrospectively analyzed. The operating time was determined based on the median pneumoperitoneum time. Surgical procedures with a pneumoperitoneum time of ≥130 min were defined as having prolonged pneumoperitoneum time. Multiple logistic regression analyses were performed to identify the preoperative factors affecting the prolonged pneumoperitoneum time, and risk stratification was performed based on these factors. RESULTS: Multiple logistic regression analyses revealed that a total number of renal pedicle blood vessels ≥3 and a visceral fat volume ≥3000 cm3 were associated with prolonged pneumoperitoneum time of laparoscopic radical nephrectomy. Based on the multivariate analysis results, these factors were considered individually, and the cohort was stratified into three risk groups: low (0 point), intermediate (1 point), and high (2 points) risk groups. The pneumoperitoneum time was significantly prolonged as the number of risk factors increased. CONCLUSIONS: We developed a risk stratification model using preoperative factors to predict the prolonged pneumoperitoneum time of laparoscopic radical nephrectomy, which can help select suitable cases that are appropriate for each surgeon's skill level.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Laparoscopía , Neumoperitoneo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Nefrectomía/efectos adversos , Nefrectomía/métodos , Tempo Operativo , Neumoperitoneo/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVES: There is no recommended observation time for patients who have undergone radical prostatectomy for prostate cancer. This study was undertaken to determine the postoperative observation time by investigating the hazard rate for prostate-specific antigen failure and other-cause death using Weibull analysis. METHODS: We included 612 patients who underwent laparoscopic radical prostatectomy for localized prostate cancer between June 2002 and December 2017. Risk classification was categorized by the D'Amico risk classification, and the patients were divided into three age groups: <60, 60-69 and ≥70 years. The hazard rates at each point were derived using Weibull analysis. The optimal observation time after laparoscopic radical prostatectomy was determined as the intersection point at which the hazard rate of other-cause death overtakes the hazard rate of prostate-specific antigen failure. RESULTS: In all groups classified by age, the hazard rate of other-cause deaths increased over time. In contrast, the hazard rate of prostate-specific antigen failure decreased gradually. The ≥70 years age group showed the highest hazard rate. The hazard rate of prostate-specific antigen failure was highest in the high-risk group. The patients aged ≥70 and 60-69 years in the low-risk group were recommended 6 years 6 months and 14 years 8 months, respectively, for observation. The remaining patients were recommended >25 years of postsurgical observation. CONCLUSIONS: The observation time after laparoscopic radical prostatectomy could be estimated by comparing the estimated hazard rates of prostate-specific antigen failure and other-cause death based on Weibull analysis. Urologists should pay attention to age and risk classifications for optimal postoperative observation.
Asunto(s)
Neoplasias de la Próstata , Urólogos , Anciano , Humanos , Masculino , Persona de Mediana Edad , Próstata , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: Using conditional survival (CS) analysis, we investigated whether the duration of survival without biochemical recurrence (BCR) of prostate cancer after laparoscopic radical prostatectomies (LRP) affected the BCR rate. We also investigated the impact of well-known risk factors for BCR. METHODS: Between 2002 and 2014, 627 consecutive patients underwent LRPs at our institution. Prostate-specific antigen (PSA) concentrations above 0.2 ng/mL were defined as BCR. Conditional BCR-free survival rates were determined through Kaplan-Meier analysis. Assessment of potential BCR risk factors was performed using a Cox proportional hazard analysis. RESULTS: The 10-year BCR-free rates after LRP increased to 82.4%, 84.5%, 86.6%, 90.1%, and 94.7% in patients surviving 1, 2, 3, 5, and 7.5 years without BCR, respectively. Multivariate analyses of age, PSA concentrations, neoadjuvant therapy, and pathological findings were performed for all patients. In all patients, positive surgical margins (PSM) and Gleason Grade Groups (GG) ≥ 4 were independent risk factors for BCR (p < 0.001, hazard ratio [HR] = 2.45; and p < 0.001, HR = 2.83, respectively,). Similarly, PSM and GG ≥ 4 were significant risk factors in patients surviving 1-5 years without BCR. No clear risk factors were observed in patients surviving > 5 years without BCR after LRPs. CONCLUSIONS: The BCR-free rate increased with time after LRP. It is recommended that patients with PSM, GG ≥ 4, or with both factors are strictly monitored for 5 years postoperatively. CS analysis is particularly useful for predicting the postoperative course of patients.
Asunto(s)
Laparoscopía , Neoplasias de la Próstata , Humanos , Japón/epidemiología , Masculino , Clasificación del Tumor , Recurrencia Local de Neoplasia , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: This study evaluated the impact of sarcopenia and psoas major muscle volume on the survival of patients with upper urinary tract urothelial carcinoma who had undergone radical nephroureterectomy. METHODS: We reviewed data from 110 patients treated with radical nephroureterectomy in our department between June 2007 and February 2017. Psoas major muscle volume was quantified based on computed tomography data using Synapse Vincent software. The psoas major muscle volume index was calculated as psoas major muscle volume/height squared (cm3/m2). We analysed relapse-free survival, cancer-specific survival and overall survival after radical nephroureterectomy to identify factors that predicted patient survival. RESULTS: The median psoas major muscle volume index was 121.5 cm3/m2, and the psoas major muscle volume index was <100 cm3/m2 in 34 of 110 patients (30.9%). Multivariate analysis indicated that ≥pT3-stage cancer, lymphovascular invasion and a psoas major muscle volume index of <100 cm3/m2 were independent predictors of shorter relapse-free survival, cancer-specific survival and overall survival. Using these factors, patients were stratified into three groups: low, intermediate and high risks for relapse-free survival, cancer-specific survival and overall survival. CONCLUSIONS: Low psoas major muscle volume resulting from sarcopenia, high T stage and the presence of lymphovascular invasion was associated with poor survival in patients with urinary tract urothelial carcinoma who had undergone radical nephroureterectomy, supporting the use of psoas major muscle volume as a new objective prognostic marker.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Carcinoma de Células Transicionales/cirugía , Humanos , Recurrencia Local de Neoplasia/cirugía , Nefroureterectomía , Pronóstico , Músculos Psoas/diagnóstico por imagen , Estudios Retrospectivos , Neoplasias Ureterales/diagnóstico por imagen , Neoplasias Ureterales/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias Urológicas/diagnóstico por imagen , Neoplasias Urológicas/cirugíaRESUMEN
BACKGROUND: Robot-assisted radical prostatectomy (RARP) has gained prominence since the da Vinci surgical system was introduced in 2000. RARP has now become a standard procedure for treating cases with localized prostate cancer. However, no study has examined its surgical time by accurately measuring the pelvic visceral fat (PVF) volume. This study aimed to investigate the factors associated with prolonged console time and surgical difficulty by RARP surgeons. METHODS: This study included 405 patients who underwent RARP between 2014 and 2019 at our institution. Given that the anatomical characteristics were considered to affect RARP, PVF and working space (WS) were estimated preoperatively by computed tomography using a 3D image analysis system. Univariate and multivariate logistic regression analyses were performed to identify the factors prolonging console time, such as body mass index (BMI), prostate volume, previous abdominal surgery, nerve-sparing procedure, PVF, and WS. We also investigated whether post-operative complications were associated with any of these factors. RESULTS: Larger PVF (p = 0.028, odds ratio (OR) 1.43), smaller WS (p < 0.001, OR 2.48), and the nerve-sparing procedure (p = 0.037, OR 1.61) were statistically significant factors associated with prolonged console time. Furthermore, higher BMI (p = 0.013, OR 1.49) and smaller pelvic width (p < 0.001, OR 2.63) were the alternative and more practical factors associated with prolonged console time. The post-operative anastomotic leakage occurrence rate increased with the number of risk factors, while post-operative complications did not change even in high-risk cases. CONCLUSION: PVF and WS are significant factors associated with prolonged console time in RARP cases. However, BMI can be as useful as PVF, since BMI significantly correlated with PVF. Additionally, pelvic width (PW) can be an alternative to WS, since PW correlated with WS. This study demonstrated that preoperative BMI and PW might predict the surgical risk and identify suitable RARP cases for novice surgeons.
Asunto(s)
Laparoscopía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Masculino , Tempo Operativo , Próstata/diagnóstico por imagen , Próstata/cirugía , Prostatectomía , Neoplasias de la Próstata/cirugíaRESUMEN
BACKGROUND: Sarcopenia, a syndrome characterized by the loss of skeletal muscle mass, has attracted attention in the field of oncology, as it reflects poor nutritional status. The present study aimed to determine the risk factors for postoperative inguinal hernia (PIH) development after robot-assisted laparoscopic radical prostatectomy (RARP) for prostate cancer, and discuss whether sarcopenia could be used as a sensitive predictor of PIH. METHODS: We reviewed the medical records of 147 patients who underwent RARP at our institution. The psoas muscle volume (PMV), as an indicator of sarcopenia, was quantified from computed tomography images using a 3-dimensional image analysis system. Multivariate cox regression analyses were performed to identify independent predictors of PIH, including pre- and peri-operative factors. RESULTS: The mean PMV was 393 cm3, and the correlation coefficient between PMV and body mass index was 0.37 (p < 0.01). The PIH-free rate at 2 years postoperatively was 78.2% among all patients. The multivariate analysis revealed that a PMV < 350 cm3 was a significant risk factor for PIH (p = 0.03; hazard ratio 2.19). Body mass index, age, prostate volume, lymph node dissection, nerve sparing, rectus muscle thickness, and console time were not related to PIH development. The PIH-free rate at 2 years postoperatively was 83.4% and 68.9% in patients with a PMV ≥ 350 cm3 and < 350 cm3, respectively (p < 0.05). CONCLUSIONS: PIH occurred significantly more frequently in patients with a PMV < 350 cm3 than in patients with a PMV ≥ 350 cm3, and a low PMV was an independent risk factor for PIH. Thus, urologists should pay attention to the cumulative incidence of IH after RARP, especially in patients with a PMV < 350 cm3.
Asunto(s)
Hernia Inguinal , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Robótica , Hernia Inguinal/cirugía , Humanos , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Próstata/diagnóstico por imagen , Próstata/cirugía , Prostatectomía/efectos adversos , Neoplasias de la Próstata/cirugía , Músculos Psoas/diagnóstico por imagen , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversosRESUMEN
PURPOSE: This study aimed to analyze technical and clinical factors related to oncological outcomes in patients with localized prostate cancer (PC) who were treated with whole-gland high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: From 2007-2014, patients diagnosed with localized PC who underwent whole-gland HIFU were consecutively included retrospectively. Biochemical failure was defined according to the Phoenix ASTRO guidelines. The relationship between oncological outcomes and technical and clinical factors was evaluated. RESULTS: The study cohort included 428 patients. The median age was 67 years, and the median prostate-specific antigen level was 7.61 ng/mL. Patient risk classifications were low (n = 102), intermediate (n = 240), and high (n = 86). Biochemical disease-free survival rates of patients with HIFU for localized PC in the total, low-, intermediate-, and high-risk groups according to D'Amico risk groups over a median follow-up period of 5 years (range 9-144) were 68.4%, 80.4%, 65.6%, and 61.6%, respectively. In multivariate logistic regression analyses to predict biochemical failure of the treatment, neoadjuvant hormonal therapy (NHT) in the high-risk group (OR 0.225, p = 0.015), and compression method in the low- (OR 0.178, p = 0.030), intermediate- (OR0.291, p < 0.0001), and high-risk (OR 0.316, p = 0.049) groups were significant factors that reduced the risk of biochemical failure after treatment. There were no significant differences in complications between patients treated with compression and those treated conventionally. CONCLUSIONS: NHT may potentially improve oncological outcomes for patients in the high-risk group, and compression methods can improve the oncological outcomes of whole-gland therapy with HIFU.
Asunto(s)
Neoplasias de la Próstata , Ultrasonido Enfocado Transrectal de Alta Intensidad , Anciano , Estudios de Seguimiento , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Mucin 1 C-terminal subunit (MUC1-C) has been introduced as a key regulator for acquiring drug resistance in various cancers, but the functional role of MUC1-C in urothelial carcinoma (UC) cells remains unknown. We aimed to elucidate the molecular mechanisms underlying the acquisition of cisplatin (CDDP) resistance through MUC1-C oncoprotein in UC cells. MUC1-C expression was examined immunohistochemically in tumor specimens of 159 UC patients who received CDDP-based perioperative chemotherapy. As a result, moderate to high MUC1-C expression was independently associated with poor survival in UC patients. Using human bladder cancer cell lines and CDDP-resistant (CR) cell lines, we compared the expression levels of MUC1-C, multiple drug resistance 1 (MDR1), the PI3K-AKT-mTOR pathway, and x-cystine/glutamate transporter (xCT) to elucidate the biological mechanisms contributing to the acquisition of chemoresistance. MUC1-C was strongly expressed in CR cell lines, followed with MDR1 expression via activation of the PI3K-AKT-mTOR pathway. MUC1-C also stabilized the expression of xCT, which enhanced antioxidant defenses by increasing intracellular glutathione (GSH) levels. MUC1 down-regulation showed MDR1 inhibition along with PI3K-AKT-mTOR pathway suppression. Moreover, it inhibited xCT stabilization and resulted in significant decreases in intracellular GSH levels and increased reactive oxygen species (ROS) generation. The MUC1-C inhibitor restored sensitivity to CDDP in CR cells and UC murine xenograft models. In conclusion, we found that MUC1-C plays a pivotal role in the acquisition of CDDP resistance in UC cells, and therefore the combined treatment of CDDP with a MUC1-C inhibitor may become a novel therapeutic option in CR UC patients.
Asunto(s)
Carcinoma/tratamiento farmacológico , Carcinoma/genética , Cisplatino/farmacología , Resistencia a Antineoplásicos/genética , Mucina-1/genética , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/genética , Animales , Carcinoma/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias Urológicas/metabolismoRESUMEN
OBJECTIVE: We evaluated the effect of neoadjuvant chemotherapy in patients undergoing radical cystectomy for urothelial bladder cancer. METHODS: We retrospectively examined 140 consecutive patients with muscle-invasive bladder cancer (clinical stage T2 to T4 and N0) who underwent radical cystectomy with or without neoadjuvant chemotherapy at four academic institutions between January 2006 and December 2016. Patients were categorized into the neoadjuvant chemotherapy group (those who underwent treatment with any neoadjuvant chemotherapy regimen; n = 69) and the non-neoadjuvant chemotherapy group (those who did not receive any neoadjuvant chemotherapy regimen; n = 71). The primary outcome measure was overall survival. RESULTS: The 5-year overall survival rates were 58.0% and 61.8% in the neoadjuvant chemotherapy and non-neoadjuvant chemotherapy groups, respectively (P = 0.320). The 5-year overall survival rates for the neoadjuvant chemotherapy and non-neoadjuvant chemotherapy groups were 64.8% and 68.4%, respectively, among cT2N0 patients (P = 0.688) and 38.6% and 21.6%, respectively, among cT3-4aN0 patients (P = 0.290). When patients with cT3-4aN0 disease in the neoadjuvant chemotherapy group were divided into responders (Asunto(s)
Carcinoma de Células Transicionales/terapia
, Cistectomía/métodos
, Terapia Neoadyuvante/métodos
, Neoplasias de la Vejiga Urinaria/terapia
, Anciano
, Anciano de 80 o más Años
, Carcinoma de Células Transicionales/patología
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Estudios Retrospectivos
, Tasa de Supervivencia
, Resultado del Tratamiento
, Neoplasias de la Vejiga Urinaria/patología
RESUMEN
PURPOSE: Laparoendoscopic single-site donor nephrectomy (LESSDN) is a feasible and effective procedure because of its non-invasiveness and better cosmetic outcomes. However, there have been few multi-institutional studies conducted by multiple surgeons on LESSDN. We retrospectively compared the clinical data and outcomes between LESSDN and conventional laparoscopic donor nephrectomy (LDN) at multiple institutes in Japan. MATERIALS AND METHODS: From 2009 to 2015, the clinical data of 223 donors who underwent LESSDN and 151 donors who underwent LDN were collected from 10 institutes. All LESSDNs were performed transperitoneally, whereas LDNs were performed transperitoneally (P-LDN) in 75 patients and retroperitoneally (R-LDN) in 76 patients. RESULTS: In the LESSDN group, the single-incision site was pararectal in 155 (69.5%) patients and umbilical in 65 (29.1%) patients. Multiple surgeons (one to eight per institute) performed the LESSDN. No significant differences were observed between the three groups regarding estimated blood loss and warm ischemic time. The operative time was significantly shorter in the LESSDN group than in the R-LDN group (p = 0.018). No significant differences were observed regarding the rates of blood transfusion, open conversion, visceral injuries, and postoperative complications. Furthermore, no significant differences were observed regarding the dose of analgesic and the rate of delayed graft function. One patient required open conversion due to injury to the renal artery. Selection of LESS procedure was not an independent risk factor for the median serum creatinine level of above 1.27 mg/dL in recipients at 1 year after kidney transplantation. CONCLUSION: The results showed the technical feasibility of LESSDN compared with the standard LDNs in a multi-institutional and multi-surgeon setting. A few observed non-negligible complications and the significantly higher levels of serum creatinine in patients who underwent LESSDN indicate that this procedure should be employed cautiously when performed by surgeons without ample experience in performing LESS procedures.
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Endoscopía/métodos , Laparoscopía/métodos , Nefrectomía/métodos , Recolección de Tejidos y Órganos/métodos , Anciano , Analgésicos/uso terapéutico , Pérdida de Sangre Quirúrgica , Creatinina/sangre , Endoscopía/efectos adversos , Femenino , Supervivencia de Injerto , Humanos , Japón , Trasplante de Riñón/métodos , Laparoscopía/efectos adversos , Donadores Vivos , Masculino , Persona de Mediana Edad , Nefrectomía/efectos adversos , Tempo Operativo , Complicaciones Posoperatorias , Espacio Retroperitoneal , Estudios Retrospectivos , Cirujanos , Recolección de Tejidos y Órganos/efectos adversos , Resultado del Tratamiento , Isquemia TibiaRESUMEN
Multiparametric magnetic resonance imaging (mpMRI) has been increasingly used to diagnose clinically significant prostate cancer (csPC) because of its usefulness in combination with anatomic and functional data. MRI-targeted biopsy, such as MRI-transrectal ultrasound (TRUS) fusion image-guided prostate biopsy, has high accuracy in the detection and localization of csPC. This novel diagnostic technique contributes to the development of tailor-made medicine as focal therapy, which cures the csPC while preserving the anatomical structures related to urinary and sexual function. In the early days of focal therapy, TRUS-guided systematic biopsy was used for patient selection, and treatment was performed for patients with low-risk PC. With the introduction of mpMRI and mapping biopsy, the treatment range is now determined based on individualized cancer localization. In recent prospective studies, 87.4% of treated patients had intermediate- and high-risk PC. However, focal therapy has two main limitations. First, a randomized controlled trial would be difficult to design because of the differences in pathological features between patients undergoing focal therapy and radical treatment. Therefore, pair-matched studies and/or historical controlled studies have been performed to compare focal therapy and radical treatment. Second, no long-term (≥ 10-year) follow-up study has been performed. However, recent prospective studies have encouraged the use of focal therapy as a treatment strategy for localized PC because it contributes to high preservation of continence and erectile function.
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Biopsia Guiada por Imagen/métodos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Estudios de Seguimiento , Humanos , Masculino , Selección de Paciente , Estudios Prospectivos , Neoplasias de la Próstata/terapia , Ultrasonografía/métodosRESUMEN
BACKGROUND: We evaluated clinical outcomes of region target focal therapy with high-intensity focused ultrasound (HIFU) for the localized prostate cancer (PCa) based on magnetic resonance imaging-based biopsy and systematic prostate biopsy for Asian. METHODS: We prospectively recruited patients with localized PCa, located their significant tumors using MRI-transrectal ultrasound (TRUS) elastic fusion image-guided transperineal prostate biopsy and 12-cores transperineal systematic biopsy, and focally treated these regions in which the tumors were located in the prostate using HIFU. Patients' functional and oncological outcomes were analyzed prospectively. RESULTS: We treated 90 men (median age 70 years; median PSA level 7.26 ng/ml). Catheterization was performed within 24 h after the treatment in all patients. Biochemical disease-free rate was 92.2% during 21 months follow-up when use of Phoenix ASTRO definition. In follow-up biopsy, significant cancer was detected in 8.9% of the patients in un-treated areas. Urinary functions, including international prostate symptom score (IPSS) (P < 0.0001), IPSS quality of life (QOL) (P = 0.001), overactive bladder symptom score (OABSS) (P < 0.0001), EPIC urinary domain (P < 0.0001), maximum urinary flow rate (P < 0.0001), and IIEF-5 (P = 0.001), had significantly deteriorated at 1 month after treatment, but improved to preoperative levels at 3 or 6 months. Rates of erectile dysfunction and ejaculation who had the functions were 86% and 70%, respectively, at 12 months after treatment. CONCLUSIONS: The present treatment for Asian would have similar oncological and functional outcomes to those in previous reports. Further large studies are required to verify oncological and functional outcomes from this treatment for patients with localized PCa.
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Biopsia Guiada por Imagen/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Ultrasonografía Intervencional/efectos adversos , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/etiologíaRESUMEN
OBJECTIVES: To evaluate postoperative pain and esthetic outcomes in patients undergoing transumbilical laparoscopic adrenalectomy with wound closure using 2-octyl cyanoacrylate. METHODS: A total of 26 patients who underwent laparoscopic adrenalectomy with the transumbilical approach and agreed to participate in this study were included. Patients were randomly divided into two groups: the 2-octyl cyanoacrylate group (Glue group) or the non-use group (non-Glue group). A single surgeon (AM) carried out all procedures between 2014 and 2017. RESULTS: There were no significant differences in the clinical background of the Glue and non-Glue groups. The number of patients with moderate or high levels of pain in the resting/moving period on postoperative days 1, 2 and 3 was 6/10 (46%/77%), 6/9 (46%/69%) and 3/5 (23%/38%) in the non-Glue group, and 5/7 (38%/54%), 2/7 (15%/54%) and 1/3 (8%/23%) in the Glue group. These differences were not significant. In the subgroup analysis of patients aged <50 years, the numbers were 4/6 (57%/86%), 5/7 (71%/100%) and 3/5 (43%/71%) in the non-Glue group, and 3/4 (33%/44%), 1/4 (11%/44%) and 0/1 (0%/11%) in the Glue group in the resting/moving period. On postoperative days 2 and 3, these differences were significant (P = 0.035 and 0.037 in the resting period, and P = 0.017 and 0.013 in the moving period). CONCLUSIONS: 2-octyl cyanoacrylate can be used safely for laparoscopic adrenalectomy with the transumbilical approach, and might be useful for reducing postoperative pain in patients aged <50 years.
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Laparoscopía , Adhesivos Tisulares , Adrenalectomía , Anciano , Cianoacrilatos , Humanos , Suturas , Adhesivos Tisulares/efectos adversosRESUMEN
OBJECTIVE: To evaluate functional outcomes over a year for benign prostatic hyperplasia treated with thulium laser enucleation of the prostate or bipolar transurethral resection of the prostate. METHODS: In this study, we prospectively included 140 patients who were treated for benign prostatic hyperplasia from April 2017 to February 2019. A randomization list was used for non-blind assignment to treatment groups (thulium laser enucleation of the prostate or bipolar transurethral resection of the prostate). The International Prostate Symptom Score, International Prostate Symptom Score quality of life, Overactive Bladder Symptom Score, uroflowmetry and International Index of Erectile Function-5 were used for the assessment of outcomes. Scores were taken before treatment, and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: Preoperatively, characteristics of patients in the thulium laser enucleation of the prostate group (n = 70) and the bipolar transurethral resection of the prostate group (n = 70) did not significantly differ. The thulium laser enucleation of the prostate group had a lower median decrease in hemoglobin (0.10 g/dL vs 0.69 g/dL, P < 0.0001) and shorter median catheterization (2 days vs 3 days, P < 0.0001) than the bipolar transurethral resection of the prostate group. Both groups had significantly improved International Prostate Symptom Score, International Prostate Symptom Score quality of life, Overactive Bladder Symptom Score, maximum flow rate and residual urine compared with preoperative values. In the thulium laser enucleation of the prostate group, erectile function was significantly impaired at 1 month post-treatment compared with pretreatment, but improved to baseline at 3 months; however, the transurethral resection of the prostate group did not recover. However, total energy (P = 0.001) and laser irradiation time (P = 0.025) were significantly different between the patients who had preserved erectile function and those who did not after the treatment in the thulium laser enucleation of the prostate group. CONCLUSIONS: Thulium laser enucleation of the prostate is superior to bipolar transurethral resection of the prostate in resection efficacy, hemostasis, catheterization time and preservation of erectile function. However, excessive laser irradiation time in thulium laser enucleation of the prostate has the possibility to delay improvement of overactive bladder symptoms and decrease sexual function.