RESUMO
Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer, which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming toward upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics that are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.
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Síndrome de Birt-Hogg-Dubé/patologia , Montagem e Desmontagem da Cromatina/genética , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Supressoras de Tumor/genética , Síndrome de Birt-Hogg-Dubé/genética , Variações do Número de Cópias de DNA , Mutação em Linhagem Germinativa , Humanos , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Sequenciamento do ExomaRESUMO
OBJECTIVES: To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. METHODS: A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. RESULTS: Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p < 0.001; intermediate-risk: p = 0.009; low-risk: p = 0.001), whereas significant differences were observed only in the intermediate-risk group (p = 0.003) within the RP vs BT group. CONCLUSION: The results of our propensity score analysis of mid-term localized prostate cancer treatment outcomes demonstrated no significant differences in the overall survival rate. Despite the difference in biochemical failure definition between surgery and radiotherapeutic approaches, the results of this study demonstrate improved biochemical control favoring IMRT and BT as compared to RP.
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Braquiterapia , Pontuação de Propensão , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia de Intensidade Modulada , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab. METHODS: Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter ≥ 30% or not). RESULTS: There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3 ± 6.4, 115.5 ± 14.9, respectively. Lesions whose diameter decreased ≥30% at second assessment were defined as responding, and lesions whose diameter did not decrease ≥30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P = 0.025, OR: 13.087, 95%CI: 1.373-124.716). CONCLUSION: Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results. TRIAL REGISTRATION: Registered in University Hospital Medical Information Network in JAPAN [ UMIN0000008141 ], registration date: 11 Jun 2012.
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Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/imunologia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/imunologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. METHODS: We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. RESULTS: There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001). CONCLUSIONS: PD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.
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Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/biossíntese , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Receptor de Morte Celular Programada 1/biossíntese , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/tendências , Receptor de Morte Celular Programada 1/genética , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/genéticaRESUMO
BACKGROUND: Laparoscopic surgical techniques are difficult to learn, and developing such skills involves a steep learning curve. To ensure surgeons achieve a high skill level, it is important to be able to measure and assess their skills. Therefore, it is necessary to understand the performance differences between experienced and novice surgeons, as such information could be used to help surgeons learn laparoscopic skills. We examined the differences in gripping and reaction force between experienced and novice surgeons during laparoscopic surgery. METHODS: We measured the gripping force generated during laparoscopic surgery performed on pigs using forceps with pressure sensors. Several sensors, including strain gauges, accelerometers, and a potentiometer, were attached to the forceps. This study included 4 experienced and 4 novice surgeons. Each subject was asked to elevate the kidney in order to approach the renal hilus using the forceps. Throughout the experiment, we measured the gripping force and reaction force generated during the movement of the forceps in real time. RESULTS: The experienced and novice surgeons exhibited similar reaction force levels. Conversely, gripping force differed significantly between the groups. The experienced and novice surgeons exhibited mean gripping force levels of 3.06 and 7.15 N, respectively. The gripping force standard deviation values for the experienced and novice surgeons were 1.43 and 3.54 N, respectively. The mean and standard deviation gripping force values of the experienced surgeons were significantly lower than those of the novice surgeons (P = 0.015 and P = 0.011, respectively). CONCLUSIONS: This study indicated that experienced surgeons generate weaker but more stable gripping force than novice surgeons during laparoscopic procedures.
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Competência Clínica , Força da Mão , Laparoscopia/normas , Instrumentos Cirúrgicos , Urologistas , Animais , Fenômenos Biomecânicos , Internato e Residência , Fenômenos Mecânicos , Sus scrofa , Suínos , Urologia/educaçãoRESUMO
BACKGROUND: Recently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy. METHODS: A total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm2) by the square of the body height (m2). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery. RESULTS: The median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm2/m2 in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p < 0.001). Based on the differences in gender, we analyzed 63 male patients for a further analysis. In male patients, those hospitalized longer showed a significantly smaller PMI than those normally discharged (377 ± 93.1 vs. 425 ± 83.4; p = 0.04). Similarly, male patients with a small PMI (<400) had a significantly worse overall survival (p = 0.02) than those with a large PMI (≥400). CONCLUSIONS: The presence of sarcopenia was found to be associated with significantly longer hospitalization after radical cystectomy in male patients. Furthermore, in men, a PMI <400 may suggest a significantly worse prognosis.
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Cistectomia , Tempo de Internação/estatística & dados numéricos , Músculos Psoas/anatomia & histologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Cistectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Músculos Psoas/patologia , Estudos Retrospectivos , Sarcopenia/complicações , Sarcopenia/patologia , Neoplasias da Bexiga Urinária/complicaçõesRESUMO
BACKGROUND: To investigate the impact of biological gender on operative parameters, especially operative time, in laparoscopic partial nephrectomy (LPN) for T1 renal tumor. METHODS: One hundred and eleven (28 female and 83 male) patients and 64 (20 female and 44 male) patients with renal tumors suspected to be RCC cT1aN0M0 who underwent retroperitoneal and transperitoneal LPN, respectively, were analyzed. The influence of sex on operative factors including retroperitoneal fat tissue thickness, determined on CT, was analyzed. The correlation between operative time and gender was evaluated by unpaired t-test and linear logistic regression model. RESULTS: In both retroperitoneal and transperitoneal LPN, the retroperitoneal fat tissue thickness was greater in men than in women. In retroperitoneal LPN, the operative time was significantly longer in men than in women. In contrast, in transperitoneal LPN, no gender difference was observed in regard to the operative time. In retroperitoneal LPN, linear logistic regression assessment showed that gender, retroperitoneal fat tissue thickness, and tumor size were significantly associated with operative time. Coefficient of determination of the prediction model was 0.317. CONCLUSIONS: The operative time of retroperitoneal LPN is significantly correlated with gender, maximum tumor diameter, and retroperitoneal fat tissue thickness. We have developed a prediction model for the operative time of retroperitoneal LPN based on preoperative parameters. Interestingly, in transperitoneal LPN, a gender difference in operative time was not apparent, and also predicting operative time might be difficult.
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Gordura Abdominal/metabolismo , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Adulto , Idoso , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Espaço Retroperitoneal , Estudos Retrospectivos , Caracteres Sexuais , Resultado do TratamentoRESUMO
BACKGROUND: There is no reliable biomarker for predicting the prognosis of patients who undergo radical cystectomy for bladder cancer. Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) could function as a useful prognostic factor in several types of malignancies. This study aimed to assess the usefulness of NLR in bladder cancer. METHODS: A total of 74 patients who underwent radical cystectomy in our institutions from 1999 to 2014 were analyzed. The NLR was calculated using the patients' neutrophil and lymphocyte counts before radical cystectomy. An immunohistochemical analysis was also performed to detect tumor infiltrating neutrophils (CD66b) and lymphocytes (CD8) in bladder cancer specimens. RESULTS: A univariate analysis showed that the patients with a high NLR (≥2.38; HR = 4.84; p = 0.007), high C-reactive protein level (>0.08; HR = 10.06; p = 0.030), or pathological lymph node metastasis (HR = 4.73; p = 0.030) had a significantly higher risk of cancer-specific mortality. Kaplan-Meier and log-rank tests further revealed that NLR was strongly correlated with overall survival (p = 0.018), but not progression-free survival (p = 0.137). In a multivariate analysis, all of these were found to be independent risk factors (HR = 4.62, 10.8, and 12.35, respectively). The number of CD8-positive lymphocytes was significantly increased in high-grade (p = 0.001) and muscle-invasive (p = 0.012) tumors, in comparison to low-grade and non-muscle-invasive tumors, respectively. CONCLUSIONS: The NLR predicted the prognosis of patients who underwent radical cystectomy and might therefore function as a reliable biomarker in cases of invasive bladder cancer.
Assuntos
Contagem de Leucócitos , Linfócitos , Neutrófilos , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Biomarcadores , Linfócitos T CD8-Positivos/patologia , Quimioterapia Adjuvante , Cistectomia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapiaRESUMO
OBJECTIVES: To assess trifecta outcomes for laparoscopic partial nephrectomy for clinical T1a renal masses. METHODS: A total of 63 patients who underwent laparoscopic partial nephrectomy for clinical T1a renal masses by a single surgeon between January 2007 and December 2012 were evaluated. Demographic and perioperative data were collected and statistically analyzed. We retrospectively evaluated trifecta outcomes. Multivariable logistic regression models were used to analyze predictors of trifecta outcomes. Trifecta outcomes were defined as the combination of total ischemia time <25 min, negative surgical margins and no surgical complications. RESULTS: Of the 63 patients, 39 (62%) achieved trifecta. A total of 21 patients had total ischemia time ≥25 min, four patients had positive surgical margins and two patients had surgical complications. Tumor size (P < 0.001), distance from the urine collecting system or sinus (P < 0.001) and surgeon's learning curve (P < 0.01) were significantly different between the trifecta and no-trifecta group. Multivariate analysis showed tumor size and surgeon's learning curve to be independent predictors of trifecta outcomes. CONCLUSIONS: Tumor size and surgeon's learning curve seems to be strong predictors of trifecta outcomes after laparoscopic partial nephrectomy in T1a renal masses.
Assuntos
Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Laparoscopia , Nefrectomia , Idoso , Feminino , Humanos , Curva de Aprendizado , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Introduction: Low-grade fibromyxoid sarcoma is an uncommon deep-seated soft-tissue sarcoma that occurs rarely in young adults and children. Although surgical resection provides a long-term prognosis, late local recurrence and metastasis may occur. Case presentation: A 44-year-old woman with no prior medical history presented with breathing and abdominal discomfort. Contrast-enhanced computed tomography scan revealed a retroperitoneal tumor protruding into the thoracic cavity and pleural effusion on the left side. Tumor biopsy revealed sarcoma. We performed complete resection of the tumor along with part of the diaphragm and replaced the diaphragm with a prosthetic patch. Histopathologic findings indicated low-grade fibromyxoid sarcoma. The patient experienced no postoperative complications and received no adjuvant therapy. Furthermore, she survived 4 years after surgery without recurrence. Conclusion: Complete surgical resection is effective for low-grade fibromyxoid sarcoma; therefore, it is important to plan appropriately for complete resection when biopsy reveals malignant findings.
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Introduction: Inflammatory myofibroblastic tumors are difficult to diagnose because of the lack of specific indicators. We describe a diagnostically challenging case of an inflammatory myofibroblastic tumor primary to the peritoneum. Case presentation: The patient was a 25-year-old male who presented at our hospital with lower abdominal pain. Computed tomography revealed a mass lesion 80 mm in diameter just above the bladder. This was suspected to be a bleeding tumor of the urachus. Since malignancy could not be ruled out, surgery was planned. This revealed a fragile tumor arising from the peritoneum. Following its removal, the tumor was diagnosed by histopathological analysis as an inflammatory myofibroblastic tumor. Conclusion: We describe a case of inflammatory myofibroblastic tumor primary to the peritoneum diagnosed by histopathology. Inflammatory myofibroblastic tumor should be considered in the differential diagnosis of abdominal wall and anterior bladder tumors.
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INTRODUCTION: The number of facilities adopting intracorporeal urinary diversion (ICUD) using robots instead of extracorporeal urinary diversion (ECUD) is increasing. However, guidance on how to introduce robot-assisted radical cystectomy (RARC) + ICUD in each urological institute remains unclear. This study aimed to verify the feasibility of the transition from laparoscopic radical cystectomy (LRC) + ECUD to RARC + ICUD. METHODS: We retrospectively analyzed 26 consecutive patients who underwent ICUD with an ileal conduit after RARC between 2018 and 2020 (RARC + ICUD early group). We then compared these patients with 26 consecutive patients who underwent ECUD with an ileal conduit after LRC between 2012 and 2019 (LRC + ECUD late group) at Yokohama City University Hospital. RESULTS: In the RARC + ICUD early group compared with the LRC + ECUD late group, the median total operation time was 516 versus 532.5 min (P = .217); time to cystectomy, 191 versus 206.5 min (P = .234); time of urinary diversion with an ileal conduit, 198 versus 220 min (P = .016); postoperative maximum C-reactive protein levels, 6.98 versus 12.46 mg/L (P = .001); number of days to oral intake, 3 versus 5 days (P = .003); length of hospital stay, 17 versus 32 days (P < .001). The postoperative complication rates (within 90 days) were 23.1% and 42.3% in the RARC + ICUD early and LRC + ECUD late groups, respectively (P = .237). Clavien-Dindo classification ≥3 was noted in 1 and 4 patients in the RARC + ICUD early and LRC + ECUD late groups, respectively (P = .350). CONCLUSION: Regarding perioperative outcomes, the RARC + ICUD early group was not inferior to the LRC + ECUD late group. This study suggests the feasibility of a transition from LRC + ECUD to RARC + ICUD.
Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Cistectomia/efeitos adversos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Derivação Urinária/efeitos adversos , Complicações Pós-Operatórias/etiologia , Laparoscopia/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Prostate ductal adenocarcinoma, a rare histology observed in 0.4-0.8% of all prostate cancers, is treated similarly to acinar adenocarcinoma but tends to have a higher likelihood of metastasis, recurrence, and poorer prognosis. CASE PRESENTATION: A 73-year-old Asian-Japanese male presented with gross hematuria, with investigations revealing a prostate ductal adenocarcinoma. Subsequent radical prostatectomy indicated a Gleason score of 8 with no lymph node metastasis. Despite initial prostate-specific antigen level reductions post-prostatectomy and salvage radiation therapy due to recurring elevated prostate-specific antigen levels, no recurrence was evident until 13 years later. A tumor in the anterior urethra was identified as metastasis of his prostate ductal adenocarcinoma. CONCLUSION: This report presents an uncommon case of prostate ductal adenocarcinoma exhibiting a late recurrence in the anterior urethra 13 years post-radical prostatectomy.
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Recidiva Local de Neoplasia , Prostatectomia , Neoplasias da Próstata , Neoplasias Uretrais , Humanos , Masculino , Idoso , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Neoplasias Uretrais/patologia , Neoplasias Uretrais/cirurgia , Antígeno Prostático Específico/sangue , Carcinoma Ductal/cirurgia , Carcinoma Ductal/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologiaRESUMO
Introduction: This study aimed to identify immune mediators, including cytokines, chemokines, and growth factors, in the plasma for predicting treatment efficacy and immune-related adverse events (irAEs) in advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs). Methods: We enrolled 57 patients with aUC who were treated with the anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab after the failure of platinum-based chemotherapy between February 2018 and December 2020. Plasma levels of 73 soluble immune mediators were measured before and 6 weeks after initiating pembrolizumab therapy. The association of estimated soluble immune mediators with clinical outcomes, including overall survival (OS), progression-free survival (PFS), anti-tumor responses, and irAEs, were statistically evaluated. Results: In the multivariate analysis, levels of 18 factors at baseline and 12 factors during treatment were significantly associated with OS. Regarding PFS, baseline levels of 17 factors were significantly associated with PFS. Higher levels of interleukin (IL)-6, IL-8, soluble tumor necrosis factor receptor 1 (sTNF-R1), and IL-12 (p40), both at baseline and post-treatment, were significantly associated with worse OS. Conversely, low IL-6 and high TWEAK levels at baseline were associated with irAEs. Among identified factors, interferon (IFN) γ and IL-12 (p40) were repeatedly identified; high baseline levels of these factors were risk factors for worse OS and PFS, as well as progressive disease. Notably, using correlation and principal component analysis, factors significantly associated with clinical outcomes were broadly classified into three groups exhibiting similar expression patterns. Discussion: Measuring plasma levels of soluble immune mediators, such as IL-6, IL-8, sTNF-R1, IFNγ, and IL-12 (p40), could be recommended for predicting prognosis and irAEs in ICI-treated patients with aUC.
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BACKGROUND: To evaluate whether urine laminin-γ2 monomer (Ln-γ2m) offers a useful biomarker for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Participants comprised 297 patients, including 111 patients with NMIBC, 136 patients with benign genitourinary disease (BD) and 50 healthy donors (HD). Urine Ln-γ2m was prospectively measured and accuracy was analyzed. Receiver operating characteristic (ROC) curves were determined and area under the ROC curve (AUC) was calculated for urine Ln-γ2m, and compared to those of traditional urine tumor markers such as nuclear matrix protein 22 (NMP22), bladder tumor antigen (BTA) and cytology. The net benefits of combining urine markers were analyzed by decision curve analysis. RESULTS: Mean urine Ln-γ2m was significantly higher in NMIBC than in BD or HD. The AUC for urine Ln-γ2m was significantly higher than those for urine NMP22, BTA or cytology when comparing NMIBC with HD. In patients with low-grade NMIBC, the AUC for urine Ln-γ2m was higher than the AUCs for NMP22, BTA or cytology. A net benefit of combined examination using urine Ln-γ2m/uCRN with NMP22 was demonstrated. CONCLUSION: These results suggest urine Ln-γ2m as a potentially useful biomarker for NMIBC, particularly in cases of low-grade cancer.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Laminina , Neoplasias da Bexiga Urinária/patologia , Curva ROC , Biomarcadores Tumorais , Sensibilidade e EspecificidadeRESUMO
We report a case of metastatic micropapillary variant of the bladder that progressed from low grade non-muscle invasive bladder carcinoma. Lung, para-aortic and pelvic lymph nodes metastatic lesions were found in a 62-year-old woman, who had been followed due to non-muscle invasive bladder carcinoma. The bladder wall was found to be thick by computerized tomography (CT). She had had transurethral resection of bladder tumor (TURBT) at 60 and 61 years old, followed by intravesical therarubicin and bacille Calmette-Guérin therapy, respectively. Both TURBT specimens showed low grade, non-muscle invasive urothelial carcinoma. The thickened bladder wall was resected transurethrally and the pathological examination revealed that the recurrent tumor was entirely composed of micropapillary variant component. There must have been tiny lesions of a micro papillary variant component after the second TURBT. Several reports suggest that intravesical BCG therapy was ineffective for micropapillary variant. So the UC component was substituted for micropapillary component.
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Carcinoma Papilar/patologia , Neoplasias da Bexiga Urinária/patologia , Carcinoma Papilar/cirurgia , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia Computadorizada por Raios X , Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
Spontaneous massive retroperitoneal hemorrhage from an adrenal tumor is rare and is usually fatal if unrecognized. We report a case of spontaneous rupture of a primary adrenocortical carcinoma that occurred in a 79-year-old man. He visited our hospital with left abdominal pain. Computed tomography (CT) showed a left retroperitoneal hemorrhage. We could not find the origin of this hemorrhage. Two months later, CT showed the left adrenal tumor, and left adrenalectomy and nephrectomy were performed successfully. The histological diagnosis was adrenocortical carcinoma. He rejected adjuvant therapy. Local recurrence of the tumor was found, and right adrenal gland, brain, and mediastinal lymph node metastases were recognized 6 months after the operation. He died 11 months after the operation.
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Neoplasias do Córtex Suprarrenal/diagnóstico , Carcinoma Adrenocortical/diagnóstico , Hemorragia/etiologia , Neoplasias do Córtex Suprarrenal/complicações , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Carcinoma Adrenocortical/complicações , Carcinoma Adrenocortical/diagnóstico por imagem , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Idoso , Hemorragia/diagnóstico por imagem , Humanos , Masculino , Metástase Neoplásica , Nefrectomia , Espaço Retroperitoneal , Ruptura Espontânea , Tomografia Computadorizada por Raios XRESUMO
A right renal tumor was incidentally found in a 38-year-old woman by annual medical check up. She visited our hospital for further examination and treatment. She did not show typical symptoms of carcinoid. A computed tomography (CT) revealed a calcified solid tumor in the upper portion of the right kidney. The tumor was 6.0 cm in diameter and was not enhanced in either early or late phase. There was no evidence of extrarenal invasion or distant metastasis. Based on a clinical diagnosis of stage 1 renal cell carcinoma, laparoscopic nephrectomy was performed. The pathological diagnosis was renal carcinoid tumor. The tumor had trabecular and ribbon-like structures with a thin fibrovascular stroma. Immunohistochemicaliy, the tumor cells stained positive for chromogranin A, synaptophisin and CD56. The cell proliferation rate was estimated to be under 1% with Ki67 staining. To find the primary lesion, we performed upper and lower gastric endoscopy and chest computed tomography, but could not find any/other carcinoid tumors. At 1-year follow up, she had no evidence of local recurrence or metastasis.
Assuntos
Tumor Carcinoide/patologia , Neoplasias Renais/patologia , Adulto , Tumor Carcinoide/diagnóstico por imagem , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Adenocarcinoma of the rete testis is a rare malignant tumor with poor prognosis. We report a case of adenocarcinoma of the rete testis. A 55-year-old man became aware of discomfort in the right scrotum. Negative results were obtained for the serum markers AFP, ß-human chorionic gonadotropin (ß-HCG), and LDH. Computed tomography (CT) showed enhancement of the right testis. Radical orchiectomy was performed. Immunohistochemical examination of the resected specimen showed positive results for CEA, and adenocarcinoma of the rete testis was diagnosed. Serum CEA level was elevated. CT showed swelling of the para-aortic lymph nodes. Retroperitoneal lymph node dissection (RPLND) was performed, and serum CEA then normalized. The patient developed penile metastases 4 months after RPLND, and serum CEA level again increased. Total penile resection was performed. TIP (Paclitaxel, Ifosfamide, Cisplatin) therapy was started after lung metastasis and increased serum CEA were identified. CT after 2 cycles of TIP therapy revealed disappearance of lung metastasis and normalization of serum CEA. Five months later, CT showed recurrence of lung metastases.
Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Neoplasias Testiculares , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Testiculares/diagnóstico , Rede do Testículo/patologia , Metástase Linfática/patologia , Excisão de Linfonodo , Neoplasias Pulmonares/secundário , Adenocarcinoma/cirurgia , Orquiectomia , Pulmão/patologiaRESUMO
In prostate cancer, accurate diagnosis and grade group (GG) decision based on biopsy findings are essential for determining treatment strategies. Diagnosis by experienced urological pathologists is recommended; however, their contribution to patient benefits remains unknown. Therefore, we analyzed clinicopathological information to determine the significance of reassessment by experienced urological pathologists at a high-volume institution to identify factors involved in the agreement or disagreement of biopsy and surgical GGs. In total, 1325 prostate adenocarcinomas were analyzed, and the GG was changed in 452/1325 (34.1%) cases (359 cases were upgraded, and 93 cases were downgraded). We compared the highest GG based on biopsy specimens, with the final GG based on surgical specimens of 210 cases. The agreement rate between the surgical GG performed and assessed in our institute and the highest biopsy GG assessed by an outside pathologist was 34.8% (73/210); the agreement rate increased significantly to 50% (105/210) when biopsy specimens were reevaluated in our institute (chi-square test, P < 0.01). Multivariate logistic regression analysis showed that only the length of the lesion in the positive core with the highest GG in the biopsy was a significant factor for determining the agreement between biopsy GG and surgical GG, with an odds ratio of 1.136 (95% confidence interval: 1.057-1.221; P < 0.01). Thus, reassessment by experienced urological pathologists at high-volume institutions improved the agreement rate. However, it should be noted there is a high probability of discordance between a small number of lesions or short lesions and surgical GG.