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Vascular endothelial growth factor receptor tyrosine kinase inhibitors are known to cause perforation as one of their severe side effects, and postoperative and postradiation therapy are known risk factors. However, there are few studies on perforation following tumor shrinkage. A 78-year-old woman with postoperative recurring left collecting duct carcinoma of the right hilar lymph nodes and mediastinum underwent eight courses of nivolumab plus cabozantinib, resulting in tumor shrinkage. Three days after the last administration, she developed fever and cough and was hospitalized for right lobar pneumonia. The patient received long-term antibiotics for bronchial fistula with the destruction of the bronchial wall and secondary lung abscess. When using nivolumab plus cabozantinib combination therapy for a tumor with bronchial invasion, physicians should be aware of bronchial perforation as the tumor shrinks.
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Anilidas , Carcinoma de Células Renais , Neoplasias Renais , Piridinas , Feminino , Humanos , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Nivolumabe/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
OBJECTIVES: Laparoscopic adrenalectomy has been the gold standard surgical procedure. However, the adaptation criteria for malignant tumors and predictors of perioperative outcomes are not well defined. Therefore, this study tried to identify valid predictors for perioperative outcomes of laparoscopic adrenalectomy and consider the adaptation criteria. METHODS: We retrospectively reviewed the preoperative and perioperative data of 216 patients who underwent transperitoneal laparoscopic adrenalectomy in our hospital. Preoperative factors associated with perioperative outcomes were analyzed using multiple regression analysis. RESULTS: Among 216 patients, 165 (76.4%), 26 (12.0%), and 25 (11.6%) were suspected of having benign tumors, pheochromocytoma, and malignant tumors, respectively. Median tumor size was 25.0 mm (interquartile range 18.0-35.0); median perirenal fat thickness was 9.2 mm (interquartile range 4.9-15.6) on preoperative computed tomography scans. The median operative time was 145.5 min (interquartile range 117.5-184.0) and the median estimated blood loss was 0.0 mL (interquartile range 0.0-27.3). Perirenal fat thickness (p < 0.001), tumor size (p < 0.001), and malignant tumors (p = 0.020) were associated with operative time, and perirenal fat thickness (p = 0.038) and malignant tumors (p = 0.002) were associated with estimated blood loss. CONCLUSIONS: Perirenal fat thickness, tumor size, and malignant tumors are valid predictors of the surgical outcomes of transperitoneal laparoscopic adrenalectomy. As only perirenal fat thickness is associated with both surgical outcomes except for malignant tumors, it is a powerful predictor. Transperitoneal laparoscopic adrenalectomy for large malignant adrenal tumors with thick perirenal fat should be performed with caution.
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Neoplasias das Glândulas Suprarrenais , Laparoscopia , Humanos , Laparoscopia/métodos , Adrenalectomia/métodos , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Prostate cancer is one of the most heritable human cancers. Lynch syndrome is an autosomal dominant inheritance caused by germline mutations in DNA mismatch repair (MMR) genes, which are also associated with an increased incidence of prostate cancer. However, prostate cancer has not been defined as a Lynch syndrome-associated cancer. The proportion of Lynch syndrome patients in primary prostate cancers is unclear. In this study, we investigated MMR protein loss using universal immunohistochemical screening to determine the prevalence of Lynch syndrome in patients with localized prostate cancer who underwent radical prostatectomy. METHODS: One hundred twenty-nine surgical specimens from radical prostatectomy performed at Toranomon Hospital between 2012 and 2015 were retrospectively tested using universal screening with immunohistochemistry staining for expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. For all suspected MMR-deficient patients, germline genetic tests focusing on MMR genes were performed. RESULTS: MMR protein loss was found in only one patient (0.8%) who showed dual MSH2/MSH6 loss. This patient showed a single nucleotide pathogenic germline mutation from c.1129 C to T (p.Gln377*) at exon 7 in the MSH2 gene. He was diagnosed with a primary prostate cancer at 66 years of age. He had a documented history of Lynch syndrome (Muir-Torre syndrome) with previous colon cancer, sebaceous tumor, and keratoacanthoma as well as subsequent bladder cancer, all of which also showed dual MSH2/MSH6 loss. He also had a strong family history of colorectal and other Lynch syndrome-associated cancers. The pathological stage was pT3aN0M0, and the pathological grade was Gleason 7(4 + 3) with tertiary pattern 5. CONCLUSIONS: In this study, immunohistochemical screening of MMR proteins for Lynch syndrome was performed in a series of prostate cancer cases. The prevalence of Lynch syndrome in localized prostate cancer was 0.8%, which is low compared with other Lynch syndrome-associated cancers.
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OBJECTIVES: To assess the detection rate of putative Lynch syndrome-associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics. METHODS: A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. For all suspected mismatch repair-deficient cases, MMR genetic testing was recommended and clinicopathological features were examined. RESULTS: Loss of mismatch repair proteins was found in seven patients (5%) who were thus categorized as putative Lynch syndrome-associated upper urinary tract urothelial cancer. Five of these patients showed dual loss of MSH2/MSH6. Two patients were confirmed to be MSH2 germline mutation carriers. Histologically, all seven tumors were low-grade atypical urothelial carcinoma and showed its unique histological features, such as an inverted papilloma-like growth pattern and a villous to papillary structure with mild stratification of tumor cells. Six tumors had no invasion of the muscularis propria. No recurrence or cancer-related deaths were reported in these seven patients. Just three patients met the revised Amsterdam criteria. CONCLUSIONS: This is the first report that universally examined mismatch repair immunohistochemical screening for upper urinary tract urothelial cancers. The prevalence (5%) of putative Lynch syndrome-associated upper urinary tract urothelial cancers is much higher than we had expected. We ascertained that putative Lynch syndrome-associated upper urinary tract urothelial cancers were clinically in the early stage and histologically classified into low-grade malignancy with its characteristic pathological features. The clinicopathological characteristics that we found in the present study could become additional possible markers in the diagnosis of Lynch syndrome-associated upper urinary tract urothelial cancers.
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Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Detecção Precoce de Câncer/métodos , Neoplasias Urológicas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/cirurgia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA/genética , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/genética , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Testes Genéticos , Humanos , Imuno-Histoquímica , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/análise , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/análise , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/análise , Proteína 2 Homóloga a MutS/genética , Mutação , Nefroureterectomia , Prevalência , Estudos Retrospectivos , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/genética , Neoplasias Urológicas/cirurgiaRESUMO
Background: The epidemiology of metastases from rare genitourinary cancer and metastases to genitourinary organs from other primary neoplasms remains poorly understood. Objective: To investigate the epidemiology of rare genitourinary metastases from rare genitourinary organ-type cancer and to genitourinary organs using data from a large national autopsy registry in Japan. Design setting and participants: A secondary analysis of the data reported in the Annual of the Pathological Autopsy Cases in Japan and the Japanese Mortality Database from 1993 to 2020 was performed. Outcome measurements and statistical analysis: Via a retrospective epidemiologic analysis, we evaluated the frequency (probability of occurrence [number per person]) and proportion (percentage) of metastases from upper urinary tract, adrenal, testicular, urethral, and penile cancers. Moreover, the sites of primary tumors metastasizing to genitourinary organs were examined. Results and limitations: In Japan, the mortality rate of upper urinary tract cancer is increasing rapidly. In the integrated database with 365 099 autopsies and 835 959 metastatic organs, the major metastatic sites (range of frequency ratios) of rare genitourinary organ-type cancers were the lungs (0.38-0.47), liver (0.21-0.56), bone (0.16-0.33), adrenal gland (0.10-0.20), peritoneum (0.0-0.16), and kidneys (0.07-0.22). The major primary sites (range of proportions) of genitourinary organ metastases were the respiratory tract (5.6-34.0%), stomach (4.7-27.0%), hematologic site (0.9-24.9%), lymphoid (2.4-22.2%), bladder (0.8-20.0%), prostate (0.7-14.1%), rectal (2.0-11.7%), and pancreas (2.6-11.0%). The cancers with a high likelihood of genitourinary metastasis were respiratory and stomach cancers. However, the study lacked individual-level information, and there might be a concomitant selection bias in this autopsy study. Conclusions: This large-scale autopsy database analysis identified the epidemiology of metastasis from rare genitourinary organ-type cancer and the origins of metastasis to genitourinary organs. Patient summary: This study provides valuable metastatic epidemiologic data and clinical information that are fundamental to the mechanisms of genitourinary metastasis.
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Introduction: Robot-assisted radical cystectomy for bladder cancer that develops after curative treatment for prostate cancer has not yet been reported. Case presentation: A 65-year-old man underwent radical prostatectomy and received salvage radiotherapy after his postoperative prostate-specific antigen level failed to decrease. Nine years after radiotherapy, local recurrence and lung/bone metastases were observed, and he was started on androgen deprivation therapy. In the following year, he was diagnosed with nonmuscle invasive bladder cancer. He underwent transurethral resection of the bladder tumor once but had multiple recurrences within 3 months. As hematuria could not be controlled by transurethral surgery, he underwent robot-assisted radical cystectomy without rectal injury. Since then, there has been no recurrence of either bladder or prostate cancer. Conclusion: This is the first report of a successful robot-assisted radical cystectomy for bladder cancer that developed after local salvage radiotherapy following radical prostatectomy for prostate cancer.
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BACKGROUND: The aim of this study is to evaluate the efficacy of radical nephrectomy with thrombectomy and to identify the prognostic factors for patients with renal cell carcinoma (RCC) and inferior vena cava tumor thrombus (IVCTT). The role of the neutrophil-to-lymphocyte ratio (NLR), which has been reported to be a useful prognostic predictor for various solid cancers, was also investigated. METHODS: Fifty-five patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy in our hospital were retrospectively analyzed. The relationship between clinical characteristics and surgical outcome was examined using the Kaplan-Meier method. Univariate and multivariate analyses were carried out to determine the prognostic factors. RESULTS: The median follow-up time after surgery was 44.2 months. Twenty-seven patients died of RCC, and 4 died of other disease at last follow-up. There were no patients with postoperative pulmonary embolism (PE) or deaths from PE. The median cancer-specific survival (CSS) and overall survival (OS) were 81.0 (95% confidence interval [CI]: 42.0-103.2) and 69.0 (95% CI: 34.3-81.5) months, respectively. Significant prognostic factors for CSS were distant metastasis (p = 0.045) and NLR ≥ 2.9 (p = 0.009). The only independent predictor for OS was the NLR ≥ 2.9 (p = 0.034). CONCLUSIONS: A high preoperative NLR level was an independent poor prognostic factor influencing CSS and OS of patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy. The NLR may be an available biomarker that helps with preoperative risk stratification.
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Carcinoma de Células Renais , Neoplasias Renais , Trombose Venosa , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Prognóstico , Estudos Retrospectivos , Neutrófilos , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Nefrectomia/métodos , Linfócitos , Complicações Pós-Operatórias/cirurgiaRESUMO
Introduction: The effectiveness of nivolumab plus cabozantinib for metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus remains unclear. Case presentation: A 77-year-old male was diagnosed with right papillary renal cell carcinoma with a metastatic lesion on Gerota's fascia, lymph node metastasis, and inferior vena cava tumor thrombus. He was treated with nivolumab plus cabozantinib. As all lesions regressed enough to permit complete resection, radical nephrectomy, thrombectomy, and retroperitoneal lymph node dissection were performed. No viable malignant cells were identified histopathologically. Despite the discontinuation of nivolumab plus cabozantinib, there has been no recurrence for 9 months. Conclusion: Nivolumab plus cabozantinib has effectiveness for metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus.
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BACKGROUND: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare RCC subtype, and FH-deficient RCC may be misdiagnosed as another type of RCC, such as type 2 papillary RCC or collecting duct carcinoma. FH and 2-succinocysteine (2SC) are useful diagnostic markers for FH-deficient RCC and can be measured using immunohistochemistry (IHC). CASE REPORT: A 30-year-old female with 3-month history of fatigue and left-flank mass was diagnosed with a 20×13×10 cm left-side renal mass with massive inferior vena cava (IVC) tumor thrombus that extended into the right atrium. She underwent nephrectomy and IVC thrombectomy, and a pathological diagnosis of type 2 papillary RCC was made. Four months after the surgery, computed tomography scan showed multiple liver metastases not observed immediately after surgery. Systemic treatment with sorafenib was initiated; however, she did not respond and died 3 months after treatment. Subsequent re-review of hematoxylin and eosin-stained sections indicated morphologic characteristics consistent with FH-deficient RCC, and IHC staining was negative for FH but positive for 2SC, indicating a diagnosis of FH-deficient RCC. Further immunological analyses revealed the loss of HLA-class I, b2 microglobulin, and HLA-DR antigens in cancer cells. In addition, a few CD8-positive cytotoxic T cells and CD163-positive tumor-associated macrophages were noted. CONCLUSION: An immunosuppressive tumor microenvironment that facilitates cancer immune evasion might be associated with the rapid progression and poor prognosis in our patient. Further investigation of the tumor immune microenvironment in patients with FH-deficient RCC is warranted.
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Introduction: The effectiveness of nivolumab plus ipilimumab for metastatic renal cell carcinoma with inferior vena cava tumor thrombus remains unclear. Case presentation: A 75-year-old male was diagnosed with metastatic renal cell carcinoma with inferior vena cava tumor thrombus and treated with nivolumab plus ipilimumab. The renal mass and thrombus regressed and all pulmonary nodules except for one lesion diminished. To avoid thrombotic complications, radical nephrectomy and thrombectomy were performed. No viable malignant cells were revealed histopathologically. Although nivolumab was continued after the surgical interventions, the remaining lesion did not change. Considering the discontinuation of nivolumab, metastasectomy was performed, and no viable malignant cells were revealed histopathologically. There has been no recurrence after the discontinuation. Conclusion: Nivolumab plus ipilimumab could have effectiveness for metastatic renal cell carcinoma with inferior vena cava tumor thrombus.
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Selective identification of men with clinically significant prostate cancer (sPC) is a pivotal issue. Development of a risk model for detecting sPC based on the prostate imaging reporting and data system (PI-RADS) for bi-parametric magnetic resonance imaging (bpMRI) and clinical parameters in a Japanese cohort is expected to prove beneficial. We retrospectively analyzed clinical parameters and bpMRI findings from 773 biopsy-naïve patients between January 2011 and December 2016. A risk model was established using multivariate logistic regression analysis and presented on a nomogram. Discrimination of the risk model was compared using the area under the receiver operating characteristic curve. Statistical differences between the predictive model and clinical parameters were analyzed using DeLong test. sPC was detected in 343 men (44.3%). Multivariate logistic regression analysis to predict sPC revealed age (P = 0.002), log prostate-specific antigen (P < 0.001), prostate volume (P < 0.001) and PI-RADS scores (P < 0.001) as significant contributors to the model. Area under the curve was higher for the risk model (0.862), than for age (0.646), log prostate-specific antigen (0.652), prostate volume (0.697) or imaging score (0.822). DeLong test results also showed that the novel risk model performed significantly better than those parameters (P < 0.05). This novel risk model performed significantly better compared with PI-RADS scores and other parameters alone, and is thus expected to prove beneficial in making decisions regarding biopsy on suspicion of sPC.
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Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Biópsia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Nomogramas , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Curva ROC , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND/AIM: Expression of human leukocyte antigen (HLA) class I and II and CD74, which functions as a chaperone of MHC class II, play essential roles in T-cell recognition. The aim of this study was to elucidate the association between the HLAs and CD74, and their correlation with the infiltrated immune cells in renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively investigated the expression of HLA-A/B/C, HLA-DR, and CD74 in 38 patients with advanced RCC (T3/T4), and evaluated their correlations with CD4 and CD8-positive T-cell infiltration using immunohistochemistry. RESULTS: The expression of HLA-A/B/C, HLA-DR, and CD74 on cancer cells was observed in 37, 20, and 31 patients, respectively. The density of CD8- and CD4-positive T cells showed a positive correlation with HLA-DR expression. The density of CD4-positive lymphocytes was significantly associated with CD74 expression. CONCLUSION: The expression of HLA-DR, rather than CD74, on cancer cells was potentially associated with the anti-cancer immune microenvironment.
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Antígenos de Diferenciação de Linfócitos B/imunologia , Carcinoma de Células Renais/imunologia , Antígenos HLA-DR/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Neoplasias Renais/imunologia , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We experienced a case of fumarate hydratase (FH) -deficient renal cell carcinoma (RCC) suspected of hereditary leiomyomatosis renal cell carcinoma (HLRCC) and herein report our findings. A 42-year-old man with an unremarkable medical history was referred to our hospital with an initial impression of renal cancer, cT3aN2M0. He underwent a right radical nephrectomy with lymph node dissection and showed a pathological diagnosis of FH-deficient RCC, pT3aN2. Clinicopathologic features indicated the possibility of HLRCC; however,-associated RCC. genetic testing showed negative for pathogenic FH mutation.HLRCC is an autosomal dominant condition caused by an FH gene mutation on chromosome 1q43. It is also a syndrome that develops in the smooth muscles of the skin and uterus, and has a renal cancer risk of 10-16%. HLRCC-associated RCC tends to metastasize early and shows poor prognosis. In FH-deficient RCC, the possibility of HLRCC-related RCC should be considered; thus, if patients fulfill the clinical diagnostic criteria, genetic counseling and screening of HLRCC are needed. Even if genetic testing does not confirm HLRCC, FH-deficient RCC still has a poor prognosis and careful follow-up is required.
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INTRODUCTION: Cystic partially differentiated nephroblastoma is a multilocular cystic variant of Wilms tumor that always presents in children. However, we encountered an elderly patient with cystic partially differentiated nephroblastoma. Therefore, we report it. CASE PRESENTATION: A 74-year-old male presented with a left renal tumor detected with ultrasonography. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a 4 cm multilocular cystic tumor with septa, which suggested multilocular cystic renal cell carcinoma. Therefore, we performed a radical nephrectomy. The definitive diagnosis of cystic partially differentiated nephroblastoma was made with histopathological findings. After the surgical resection, no recurrence has occurred in the past 13 years. CONCLUSION: Cystic partially differentiated nephroblastoma can develop in adults, regardless of age. Furthermore, surgical resection can be used as an established treatment option in adult cystic partially differentiated nephroblastoma cases.
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A 59-year-old female experienced gross hematuria and right back pain, and she visited our hospital in March 2015. Abdominal computed tomography (CT) showed bilateral renal pelvic calculi; the right stone was 15 mm and the left stone was 18 mm in diameter. She had ulcerative colitis and had been taking salazosulfapyridine (SASP) for about 30 years. Urinalysis showed aciduria and deposition of urate crystals. An abdominal X-ray picture did not show a calculus shadow. We suspected uric acid calculus and started treatment with urinary alkalizer and uric acid production inhibitor.Three months later, abdominal CT showed enlargement of the bilateral renal pelvic calculi; the right stone was 25 mm and the left stone was 24 mm in diameter. She also complained of worse right back pain and underwent transurethral ureterolithotripsy for the right renal pelvic stone. The stone was orange, comparatively soft, and chipped down until it was approximately half of its original size. The stone analysis suggested suspected drug-induced urolithiasis, but not uric acid calculus. Thus, we investigated the stone and SASP using infrared spectroscopy, and the infrared absorption pattern was similar in both. The stone analysis demonstrated drug-induced urolithiasis induced by SASP.The patient's ulcerative colitis therapy was switched to mesalazine, and the amount of urinary alkalizer was increased. Abdominal CT 3 months thereafter showed dissipation of bilateral renal pelvic calculi. The patient did not take any preventative medication, and there was no recurrence of urolithiasis.
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Colite Ulcerativa/tratamento farmacológico , Nefrolitíase/induzido quimicamente , Sulfassalazina/efeitos adversos , Feminino , Humanos , Litotripsia , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Nefrolitíase/terapia , Resultado do TratamentoRESUMO
INTRODUCTION: To clarify the mechanisms responsible for running-induced asymptomatic gross hematuria. CASE PRESENTATION: We identified 12 patients who visited our outpatient clinic with hematuria after running as a chief complaint. In 9 of 12 patients (75%), cystoscopic findings revealed mucosal contusions at the center of the posterior wall. Our examination including cystoscopy and magnetic resonance imaging revealed that this bladder contusion development was caused by the repeated contact of the bladder posterior wall against the fixed bladder neck by vertical motion in the empty bladder lumen during running. All patients with bladder contusion were male because the bladder neck is more firmly fixed to the pelvic floor by the protruding prostate in men than women. Gross hematuria in all patients quickly resolved without treatment after running cessation. CONCLUSION: This is the first report in which cystoscopic findings showed that running-induced macroscopic hematuria can be frequently caused by traumatic bladder contusion.
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OBJECTIVE: The aim of this study was to investigate the efficacy and safety of tadalafil add-on therapy with α1 -adrenoceptor antagonists. METHODS: Patients with persistent storage symptoms refractory to α1 -adrenoceptor antagonists for benign prostatic hyperplasia were enrolled in the study. Patients were randomly assigned to either a 5 mg tadalafil or 5 mg solifenacin treatment group for 12 weeks. International Prostate Symptom Score, Overactive Bladder Symptom Score, urinary flow rates, residual urine volume, and blood pressure were measured prospectively before treatment and after 4 and 12 weeks of treatment. Changes from baseline were compared between groups. The rate of treatment discontinuation due to adverse effects was evaluated. RESULTS: Of the 75 patients recruited to the study, 38 and 37 were assigned to the tadalafil and solifenacin groups, respectively. There were no significant difference in baseline characteristics between the two groups. The change in the amount of residual urine volume was significantly larger in the solifenacin- than tadalafil-treated group; other parameters, including lower urinary tract symptoms and uroflowmetry measures, did not differ significantly between the two groups. Seven (18%) and 12 (32%) patients in the tadalafil and solifenacin groups, respectively, discontinued treatment because of adverse events. The main reasons for discontinuation in the tadalafil group were stomach discomfort or nausea and dizziness or vertigo; voiding difficulty and constipation were the main reasons for discontinuation in the solifenacin group. There was no significant difference in blood pressure fluctuations from baseline between the two groups. CONCLUSIONS: Tadalafil add-on therapy was not inferior to solifenacin add-on therapy in terms of effect and safety. Therefore, tadalafil could be an alternative add-on drug for patients with persistent lower urinary tract symptoms refractory to α1 -adrenoceptor antagonists.
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Hiperplasia Prostática/complicações , Prostatismo/tratamento farmacológico , Succinato de Solifenacina/uso terapêutico , Tadalafila/uso terapêutico , Agentes Urológicos/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prostatismo/etiologia , Índice de Gravidade de Doença , Succinato de Solifenacina/efeitos adversos , Tadalafila/efeitos adversos , Agentes Urológicos/efeitos adversosRESUMO
OBJECTIVES: Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT). MATERIAL AND METHODS: Thirty-five patients with nonmetastatic ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical (IHC) analyses were performed for the expression of BAP1 protein, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate analyses of the associations between disease-free survival (DFS) and clinical variables including BAP1 protein expression, tumor size, Karnofsky performance status (KPS) score, and the extension level of the tumor thrombus were performed using a Cox proportional hazard model. RESULTS: The median follow-up time was 58.8 months (range: 2-130 months). The median age was 68 years (range: 37-80 years). The median size of the primary tumor was 9.6cm (range: 3.0-15.0cm). The IVCTT extended above and below the diaphragm in 10 (28.6%) and 25 (71.4%) patients, respectively. The KPS score was>80 in 23 patients (65.7%). BAP1 protein expression on IHC was positive in 24 cases (68.8%) and negative in 11 cases (31.2%). The median overall survival in cases with BAP1-negative and -positive tumor on IHC staining were 44.7 and 81.5 months, respectively (P = 0.052). BAP1-negative tumor on IHC staining was associated with a significantly shorter DFS than BAP1-positive tumor (median DFS = 10.0 vs. 26.0 months, respectively; P = 0.011). Multivariate analysis showed that only BAP1-negative tumor on IHC staining was significantly associated with shorter DFS (P = 0.004). CONCLUSIONS: Patients whose tumors had loss of BAP1 protein expression were significantly associated with poor prognosis in patients with ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy.
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Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , Veia Cava Inferior/anormalidades , Trombose Venosa/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Trombose Venosa/patologiaRESUMO
(Background) Multiple renal angiomyolipoma (AML) may develop concurrently with tuberous sclerosis complex (TSC) and lung lymphangioleiomyomatosis (LAM). In recent years, an increase in subjects undergoing chest computed tomography examinations, including medical examinations, has been accompanied by an increase in LAM cases that are diagnosed while still asymptomatic. Surgical treatment may also be performed for renal AML to prevent bleeding. We clarified the clinical features of AML that is complicated by LAM, and discussed the significance of screening for LAM. (Methods) Between January 1, 2006 and April 30, 2014 two groups, comprising 7 patients with LAM (LAM-AML group) and another 26 patients without LAM (sporadic AML group), were compared with regard to findings for renal AML such as imaging examinations, pathological features, and treatment course. Screening for LAM was chest CT scanning. (Results) In the LAM-AML group, there were younger and more female cases and tumors tended to be multiple, large and bilateral. 85.7% of cases underwent surgery. On the other hand, in the sporadic group 73.1% of cases were followed up without treatment. There was no preoperative lung screening except the one TSC case and all 5 LAM cases were diagnosed postoperatively. One LAM patient was symptomatic and eventually required lung transplantation, while all other LAM cases were handled by monitoring the course, without treatment. (Conclusion) Many cases of asymptomatic LAM are untreated. However, the poor prognosis, risk of a need for general anesthesia, and potential for renal sparing by selection of pharmacotherapy must be taken into account. In that light-especially in the case of young women-patients with multiple renal AML should undergo preoperative screening for LAM.
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OBJECTIVES: To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value. METHODS AND MATERIALS: We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins. We retrospectively analyzed the associations between the expression of BAP1 and PBRM1 and overall survival (OS). RESULTS: The most common first metastatic sites were lung (68.3%) and lymph node (12.2%). BAP1 protein expression was negative in 8 (19.5%) primary sites and in 11 (26.8%) metastatic sites. PBRM1 protein expression was negative in 9 (22.0%) primary sites and in 11 (26.8%) metastatic sites. The incidences of intratumoral heterogeneity for BAP1 and PBRM1 protein expression in primary/metastatic sites were 9.8%/2.4% and 24.4%/7.3%, respectively. The concordance rates between primary and metastatic sites for BAP1 and PBRM1 protein expression were 82.9% and 63.4%, respectively. Median OS from the first occurrence of metastasis in patients with BAP1-positive and BAP1-negative metastatic sites were 97 months (95% CI: 58-136) and 51 months (95% CI: 13-82), respectively (P = 0.0077). Median OS in patients with PBRM1-positive and PBRM1-negative metastatic sites were 82 (95% CI: 42-97) and 120 (95% CI: 52-120) months, respectively (P = 0.25). CONCLUSION: Intratumoral heterogeneity of BAP1 protein expression is more frequent in primary tumor than in metastatic sites. The loss of BAP1 protein expression in metastatic sites predicts poor prognosis in patients with ccRCC.