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1.
Br J Cancer ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611307

RESUMO

BACKGROUND: Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis. METHODS: To clarify the effects of the AXL/GAS6 axis on RCC, we herein performed a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of RCC. We further applied genome-wide mutation analyses and methylation arrays. RESULTS: Varying patterns of AXL and GAS6 expression were observed throughout primary RCC tumours and metastases. Scoring individual AXL/GAS6 levels in the tumour centre and invasive margin, namely, the AXL/GAS6 score, showed a good ability to predict the prognosis of clear cell RCC. Metastasis- and histological subtype-specific differences in the AXL/GAS6 score existed since lung metastasis and the papillary subtype were weakly related to the AXL/GAS6 axis. Cell-by-cell immunohistological assessments clarified an immunosuppressive environment in tumours with high AXL/GAS6 scores. Genomic alterations in the PI3K-mTOR pathway and DNA methylation profiling revealed distinct differences with the AXL/GAS6 score in ccRCC. CONCLUSION: The AXL/GAS6 scoring system could predict the outcome of prognosis and work as a robust biomarker for the immunogenomic state in RCC.

2.
BMC Med Genomics ; 14(1): 245, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627261

RESUMO

BACKGROUND: Ductal adenocarcinoma and neuroendocrine cancer are rare subtypes of prostate cancer with poor prognosis and limited therapeutic options. We present the first case of ductal adenocarcinoma having a neuroendocrine phenotype. CASE PRESENTATION: A 63-year-old man presented with gross hematuria and urinary retention, and his serum prostate-specific antigen level was 4.58 ng/mL. We performed transurethral resection of the prostate, and the diagnosis was ductal adenocarcinoma with a Gleason score of 5 + 4 for acinar adenocarcinoma. Magnetic resonance imaging showed local invasion of left lobe of the prostate and bone metastasis of the left trochanteric section of the femur. Multidisciplinary treatments such as androgen deprivation therapy, chemoradiation therapy, and surgery for metastatic lesions have led to long-term survival. Since next-generation sequencing revealed PTEN and RB1 co-loss and TP53 mutations, we re-evaluated the immunohistochemistry and he was found to be positive for synaptophysin. CONCLUSIONS: This is the first Japanese case of ductal adenocarcinoma with a neuroendocrine phenotype. Genetic analysis may help not only guide the therapeutic strategies, but also sometimes with the diagnosis.

3.
Eur Urol ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34627641

RESUMO

Immune checkpoint inhibitors (ICIs) have become key agents in the management of clear cell renal cell carcinoma (ccRCC), but their benefits are limited and responders remain unidentified. We investigated the significance of PARP1 in ccRCC using RNA sequencing data for 311 tumors from patients enrolled in prospective clinical trials of PD-1 blockade. Among patients treated with nivolumab (n = 181), overall survival (OS) was significantly higher in the PARP1-low group than in the PARP1-high group (p = 0.006), and PARP1 status was significantly associated with OS (hazard ratio [HR] 1.7; p = 0.007). By contrast, for patients treated with everolimus (n = 130) there was no significant difference by PARP1 status for progression-free survival (PFS; p = 0.9) or OS (p = 0.38). In subgroup analysis for PBRM1-mutated ccRCC, PFS (p = 0.016) and OS (p = 0.004) were significantly longer in the group with PARP1-low status and PBRM1 mutation in comparison to the other groups. In addition, PARP1 status was significantly associated with PFS (HR 2.6; p = 0.007) and OS (HR 3.5; p = 0.016) among patients with PBRM1-mutated ccRCC treated with nivolumab. Our study suggests that PARP1 can be used as a biomarker for predicting response to ICI treatment for patients with PBRM1-mutated ccRCC. PATIENT SUMMARY: Immune checkpoint inhibitors (ICIs) are key agents in the treatment of multiple cancers. We found that expression of the PARP1 protein was associated with survival after ICI treatment and with the response to ICI treatment in patients with clear cell kidney cancer who have a mutation of the PBRM1 gene.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34593983

RESUMO

BACKGROUND: The taxane cabazitaxel (CBZ) is a promising treatment for docetaxel-resistant castration-resistant prostate cancer (CRPC). However, the survival benefit with CBZ for patients with CRPC is limited. This study used screening tests for candidate drugs targeting CBZ-resistant-related gene expression and identified pimozide as a potential candidate for overcoming CBZ resistance in CRPC. METHODS: We established CBZ-resistant cell lines, DU145CR and PC3CR by incubating DU145 cells and PC3 cells with gradually increasing concentrations of CBZ. We performed in silico drug screening for candidate drugs that could reprogram the gene expression signature of a CBZ-resistant prostate cancer cells using a Connectivity Map. The in vivo effect of the drug combination was tested in xenograft mice models. RESULTS: We identified pimozide as a promising candidate drug for CBZ-resistant CRPC. Pimozide had a significant antitumor effect on DU145CR cells. Moreover, combination treatment with pimozide and CBZ had a synergic effect for DU145CR cells in vitro and in vivo. Microarray analysis identified AURKB and KIF20A as potential targets of pimozide in CBZ-resistant CRPC. DU145CR had significantly higher AURKB and KIF20A expression compared with a non-CBZ-resistant cell line. Inhibition of AURKB and KIF20A had an antitumor effect in DU145CR xenograft tumors. Higher expression of AURKB and KIF20A was a poor prognostic factor of TGCA prostate cancer cohort. CBZ-resistant prostate cancer tissues in our institution had higher AURKB and KIF20A expression. CONCLUSIONS: Pimozide appears to be a promising drug to overcome CBZ resistance in CRPC by targeting AURKB and KIF20A.

5.
Nat Commun ; 12(1): 5547, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545095

RESUMO

A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs.


Assuntos
Antígenos CD/metabolismo , Carcinoma de Células Renais/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Neoplasias Renais/metabolismo , Receptores Imunológicos/metabolismo , Idoso , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Fenótipo , Reprodutibilidade dos Testes
7.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360727

RESUMO

Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient's family was advised to undergo genetic counseling to consider additional RCC screening.


Assuntos
Fumarato Hidratase/deficiência , Deleção de Genes , Mutação em Linhagem Germinativa , Leiomiomatose/genética , Erros Inatos do Metabolismo/genética , Hipotonia Muscular/genética , Síndromes Neoplásicas Hereditárias/genética , Transtornos Psicomotores/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Adulto , Feminino , Fumarato Hidratase/genética , Testes Genéticos , Humanos
9.
Urol Oncol ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34454822

RESUMO

OBJECTIVE: The indications of neoadjuvant chemotherapy (NAC) for lymph node-positive upper tract urothelial carcinoma (UTUC) have not been investigated regarding improved survival outcomes. Our specific aim was to compare the clinical outcomes of clinically node-positive UTUC patients who were treated by NAC followed by radical nephroureterectomy (RNU) or upfront RNU followed by adjuvant chemotherapy (AC). MATERIALS AND METHODS: Among 966 UTUC patients, we identified 89 with clinical nodal involvement who received either NAC before RNU nor AC after upfront RNU. Cox proportional hazard models were employed to evaluate the impact of chemotherapy modality on the oncological outcomes. RESULTS: Of the patient cohort, 36 (40.4%) received NAC followed by RNU, whereas 53 (59.6%) underwent RNU followed by AC. Multivariate analysis revealed that tumor size ≥3 cm, clinical T4, and gemcitabine and cisplatin regimen were independent risk factors for disease recurrence, whereas NAC followed by RNU was an independent factor for favorable RFS. Furthermore, regarding cancer-specific survival (CSS), NAC followed by RNU remained an independent factor for favorable CSS. According to Kaplan-Meier analysis, the 1-year and 2-year RFS were 67.9% and 47.0%, respectively, in the NAC+RNU group, which were significantly higher than those in the RNU+AC group (43.9% and 24.6%, respectively, P = 0.006). Moreover, the 1-year and 2-year CSS were 80.5% and 64.2%, respectively, in the NAC+RNU group, which were higher than those in the RNU+AC group (68.6% and 48.2%, respectively, P = 0.016). CONCLUSION: For node-positive UTUC patients, NAC followed by RNU was more clinically beneficial than RNU followed by AC.

10.
Jpn J Clin Oncol ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34350454

RESUMO

BACKGROUND: We performed subgroup analyses of the AFTER I-O study to clarify the association of time-to-treatment failure (TTF) and discontinuation reason of prior immune-oncology (I-O) therapy, and molecular targeted therapy (TT) regimen with the outcomes of TT after I-O. METHODS: The data of Japanese metastatic renal cell carcinoma patients treated with TT after nivolumab (NIVO) (CheckMate 025) or NIVO + ipilimumab (IPI) (CheckMate 214) were retrospectively analyzed. The objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS) of TT after I-O were analyzed by subgroups: TTF (<6 or ≥6 months) and discontinuation reason of prior I-O (progression or adverse events), and TT regimen (sunitinib or axitinib). We also analyzed PFS2 of prior I-O and OS from first-line therapy. RESULTS: The ORR and median PFS of TT after NIVO and NIVO+IPI among the subgroups was 17-36% and 20-44%, and 7.1-11.6 months and 16.3-not reached (NR), respectively. The median OS of TT after NIVO was longer in patients with longer TTF of NIVO and treated with axitinib. Conversely, median OS of TT after NIVO+IPI was similar among subgroups. The median PFS2 of NIVO and NIVO+IPI was 36.7 and 32.0 months, respectively. The median OS from first-line therapy was 70.5 months for patients treated with NIVO and NR with NIVO+IPI. The safety profile of each TT after each I-O was similar to previous reports. CONCLUSIONS: The efficacy of TT after NIVO or NIVO+IPI was favorable regardless of the TTF and discontinuation reason of prior I-O, and TT regimen.

11.
Eur J Radiol ; 143: 109895, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34388418

RESUMO

PURPOSE: To investigate the feasibility of texture analysis of apparent diffusion coefficient (ADC) maps for differentiating fat-poor angiomyolipomas (fpAMLs) from non-clear-cell renal cell carcinomas (non-ccRCCs). METHODS: In this bi-institutional study, we included two consecutive cohorts from different institutions with pathologically confirmed solid renal masses: 67 patients (fpAML = 46; non-ccRCC = 21) for model development and 39 (fpAML = 24; non-ccRCC = 15) for validation. Patients underwent preoperative magnetic resonance imaging (MRI), including diffusion-weighted imaging. We extracted 45 texture features using a software with volumes of interest on ADC maps. Receiver operating characteristic curve analysis was performed to compare the diagnostic performance between the random forest (RF) model (derived from extracted texture features) and conventional subjective evaluation using computed tomography and MRI by radiologists. RESULTS: RF analysis revealed that grey-level zone length matrix long-zone high grey-level emphasis was the dominant texture feature for diagnosing fpAML. The area under the curve (AUC) of the RF model to distinguish fpAMLs from non-ccRCCs was not significantly different between the validation and development cohorts (p = .19). In the validation cohort, the AUC of the RF model was similar to that of board-certified radiologists (p = .46) and significantly higher than that of radiology residents (p = .03). CONCLUSIONS: Texture analysis of ADC maps demonstrated similar diagnostic performance to that of board-certified radiologists for discriminating between fpAMLs and non-ccRCCs. Diagnostic performances in the development and validation cohorts were comparable despite using data from different imaging device manufacturers and institutions.


Assuntos
Angiomiolipoma , Carcinoma de Células Renais , Neoplasias Renais , Angiomiolipoma/diagnóstico por imagem , Carcinoma de Células Renais/diagnóstico por imagem , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Humanos , Neoplasias Renais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estudos Retrospectivos
12.
Int J Clin Oncol ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34357470

RESUMO

BACKGROUND: The effects of the type of anesthesia (spinal (SA) vs. general (GA)) used for transurethral resection of bladder tumor (TURBT) on non-muscle invasive bladder cancer (NMIBC) recurrence and progression are controversial and our aim is to investigate their associations. METHODS: We identified 300 NMIBC patients who underwent initial TURBT with SA or GA. Cox's regression analysis was performed to examine the effects of anesthesia on tumor recurrence. RESULTS: Among 300 patients, 153 (51.0%) received GA and 147 (49.0%) SA. The 5-year recurrence-free survival (RFS) rate was 59.9% in the GA group, which was significantly lower than that in the SA group (74.4%, p = 0.029). GA (HR 1.57, p = 0.048), male sex (HR 2.72, p = 0.012), and tumor multiplicity (HR 1.96, p = 0.006) were independently associated with tumor recurrence. In a subgroup of 137 patients with high-risk NMIBC, the 5-year RFS rate was 50.3% in the GA group, which was significantly lower than that in the SA group (77.6%, p = 0.020), and GA remained an independent indicator of tumor recurrence (HR 2.35, p = 0.016). However, no significant differences were observed in the RFS rates of low- to intermediate-risk NMIBC patients between the GA and SA groups. CONCLUSIONS: The RFS rate was lower in NMIBC patients who received GA during TURBT than in those who received SA. Volatile anesthesia may increase tumor recurrence, particularly in high-risk NMIBC patients, which may be due to the inhibition of the immune response system during surgery.

13.
Urol Oncol ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34332846

RESUMO

PURPOSE: We herein compared the diagnostic performance of Vesical Imaging-Reporting and Data System (VI-RADS) scoring with diagnostic cystoscopy and evaluated diagnostic accuracies based on tumor locations. MATERIALS AND METHODS: Among 112 bladder cancer patients who underwent multiparametric magnetic resonance imaging and diagnostic cystoscopy preoperatively to detect bladder cancer, 61 were analyzed. VI-RADS was categorized into 5 stages by 2 radiologists (R1 and R2). Cut-off values ≥3 indicated muscle-invasive bladder cancer (MIBC). Muscle invasion (MI) was visually evaluated using diagnostic cystoscopy by 2 urologists (U1 and U2). The sensitivity and specificity of VI-RADS scores and diagnostic cystoscopy for diagnosing MI were compared. RESULTS: 16 patients (26.2%) were pathologically diagnosed with MIBC. Regarding MI diagnostic accuracy, the sensitivity/specificity of VI-RADS scores were 93.8/88.9% by R1 and 87.5/86.7% by R2, while those of diagnostic cystoscopy were 56.3/68.9% by U1 and 68.8/84.4% by U2. Therefore, the diagnostic accuracy of VI-RADS was significantly higher than that of cystoscopy, particularly for tumors located on the bladder neck, trigone, dome, and posterior and anterior walls. Over- and under-diagnosis rates were higher with VI-RADS than with diagnostic cystoscopy (25.9% vs. 14.8%) for tumors located on the lateral wall or ureteral orifice. CONCLUSION: VI-RADS had superior diagnostic performance for detecting MI, especially in tumors located at the bladder neck/trigone/dome/posterior and anterior wall. However, VI-RADS was inferior to cystoscopy in terms of MI detection for tumors located on the lateral wall or ureteral orifice. Therefore, a combination of diagnostic tools is recommended for the accurate staging of these tumors.

14.
Int J Clin Oncol ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34291367

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010-2015. METHODS: This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan-Meier methodology. RESULTS: PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1-positive patients was 30.9 months (95% CI 25.5-35.7) versus 37.5 months (95% CI 34.0-42.6) for PD-L1-negative patients (HR 1.04 [90% CI 0.89-1.22, p = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1-positive and -negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986). CONCLUSIONS: This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.

15.
Cancer Immunol Immunother ; 70(10): 3001-3013, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34259900

RESUMO

Despite the high sensitivity of renal cell carcinoma (RCC) to immunotherapy, RCC has been recognized as an unusual disease in which CD8+ T-cell infiltration into the tumor beds is related to a poor prognosis. To approach the inner landscape of immunobiology of RCC, we performed multiplexed seven-color immunohistochemistry (CD8, CD39, PD-1, Foxp3, PD-L1, and pan-cytokeratin AE1/AE3 with DAPI), which revealed the automated single-cell counts and calculations of individual cell-to-cell distances. In total, 186 subjects were included, in which CD39 was used as a marker for distinguishing tumor-specific (CD39+) and bystander (CD39-) T-cells. Our clear cell RCC cohort also revealed a poor prognosis if the tumor showed increased CD8+ T-cell infiltration. Intratumoral CD8+CD39+ T-cells as well as their exhausted CD8+CD39+PD-1+ T-cells in the central tumor areas enabled the subgrouping of patients according to malignancy. Analysis using specimens post-antiangiogenic treatment revealed a dramatic increase in proliferative Treg fraction Foxp3+PD-1+ cells, suggesting a potential mechanism of hyperprogressive disease after uses of anti-PD-1 antibody. Our cell-by-cell study platform provided spatial information on tumors, where bystander CD8+CD39- T-cells were dominant in the invasive margin areas. We uncovered a potential interaction between CD8+CD39+PD-1+ T-cells and Foxp3+PD-1+ Treg cells due to cell-to-cell proximity, forming a spatial niche more specialized in immunosuppression under PD-1 blockade. A paradigm shift to the immunosuppressive environment was more obvious in metastatic lesions; rather the infiltration of Foxp3+ and Foxp3+PD-1+ Treg cells was more pronounced. With this multiplexed single-cell pathology technique, we revealed further insight into the immunobiological standing of RCC.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Renais/genética , Imunoterapia/métodos , Neoplasias Renais/genética , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Prognóstico , Resultado do Tratamento
16.
Clin Endocrinol (Oxf) ; 95(5): 716-726, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34288003

RESUMO

OBJECTIVE: Pheochromocytoma is a rare neuroendocrine tumour that secretes catecholamines and originates in the adrenal gland. Although surgical resection is the only curative therapy for pheochromocytoma, it is associated with a risk of haemodynamic instability (HDI), such as extremely high blood pressure and/or post tumour removal hypotension and shock. We investigated the risk factors for HDI during pheochromocytoma surgery. DESIGN AND PATIENTS: Eighty-two patients who underwent laparoscopic adrenalectomy for pheochromocytoma between July 2002 and February 2020 were examined. We excluded 3 patients with bilateral disease and 11 without detailed 24 h urinary data. We defined HDI as systolic blood pressure ≥ 200 or <80 mmHg. We investigated the risk factors for HDI during laparoscopic adrenalectomy for pheochromocytoma. RESULTS: There were 29 males and 39 females with a median age of 50.5 years. Tumours were localised on the right adrenal gland in 28 patients and on the left in 40. The median tumour diameter was 37.5 mm and the median pneumoperitoneum time was 93.5 min. Twenty-five out of sixty-eight patients (37%) developed HDI. A multivariate analysis identified diabetes mellitus (DM; odds ratio: 3.834; 95% confidence interval: 1.062-13.83; p = .04) as an independent predictor of HDI. In terms of hormonal data, median 24 h urinary epinephrine levels (p = .04) and metanephrine levels (p = .01) were significantly higher in the HDI group. DM was also considered as a risk factor for prolonged HDI (p = .02). CONCLUSION: Surgeons and anaesthesiologists need to be aware of the risk of HDI and its prolongation during laparoscopic adrenalectomy for pheochromocytoma for DM patients.

17.
Int Urol Nephrol ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264473

RESUMO

PURPOSE: Iron-based phosphate binders, including ferric citrate hydrate (FCH) and sucroferric oxyhydroxide (SFOH), have been used for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. However, the long-term efficacy and safety of these agents have not yet been clearly elucidated. METHODS: Laboratory data of 56 hemodialysis patients who had been prescribed either FCH (n = 33) or SFOH (n = 23) were retrospectively examined. RESULTS: We showed that both FCH and SFOH significantly and consistently decreased serum phosphate concentrations in the patients undergoing maintenance hemodialysis during the 36-month observation period. Serum levels of calcium, intact parathyroid hormone, as well as hemoglobin levels were unaltered. No overshoot of parameters of iron metabolism, such as transferrin saturation and serum ferritin levels, was observed, and serum ferritin level remained under 300 ng/mL in most patients. A trend towards decrease in the doses of erythropoiesis-stimulating agents used and frequency of intravenous iron use was observed in both treatment groups. No severe adverse drug reactions were observed in either the patients receiving FCH or SFOH. CONCLUSION: The results of the present study suggest that the iron-based phosphate binders, FCH and SFOH, decrease serum phosphate concentrations consistently and are safe to use over the long-term in maintenance hemodialysis patients.

18.
CEN Case Rep ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34227055

RESUMO

Alström syndrome (AS) is an extremely rare disease accompanied by blindness, hearing loss, obesity, type 2 diabetes, dilated cardiomyopathy, and progressive hepatic and renal dysfunction. The life span of AS patients rarely exceeds 50 years, and thus there are very few reports describing the implementation of renal replacement therapy for these patients. We here report a case of AS patient who exhibited dilated cardiomyopathy, end-stage renal disease, and hepatic cirrhosis. He underwent hemodialysis therapy more than 3 years. Although he eventually died of amiodarone-induced multiple organ damage in the lungs and liver, the present case suggests that hemodialysis therapy can be a choice of renal replacement therapy for AS patients with end-stage renal disease.

19.
Int J Clin Oncol ; 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34086109

RESUMO

BACKGROUND: Routine use of neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP) is not recommended, but it is sometimes performed to reduce the prostate size and tumor volume or to prevent tumor progression during the wait times for surgery in clinical practice. On the other hand, the impact of NHT on the pattern of biochemical recurrence (BCR) is unknown. METHODS: We retrospectively examined 1749 consecutive patients who underwent RP between 1996 and 2017. Among the patients who met the inclusion criteria, BCR developed in 240 of non-NHT patients and in 120 of NHT patients during the mean follow-up period of 6.9 years. We examined the impact of NHT on the PSA-doubling time (DT) following BCR at different times after RP. RESULTS: The median PSA-DTs in non-NHT patients who experienced BCR in the first year after surgery, between 1 and 2 years, between 2 and 3 years, between 3 and 4 years, between 4 and 5 years, and at > 5 years were 5.5, 8.8, 11.3, 17.7, 18.2, and 18.4 months, respectively. On the other hand, those in NHT patients were 1.4, 4.1, 9.1, 13.4, 27.2, and 19.3 months, respectively. The differences of PSA-DTs in the first year after surgery (p < 0.001) and between 1 and 2 years (p = 0.005) were significant between non-NHT and NHT patients. CONCLUSION: Patients who received NHT had a higher risk of a rapid PSA increase when they experienced BCR, especially within 2 years after RP. In order to not miss the optimal timing of salvage treatment for BCR, intensive PSA follow-up is necessary.

20.
Int J Clin Oncol ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34101038

RESUMO

OBJECTIVE: The aim of this study was to evaluate the clinical significance of the on-treatment C-reactive protein (CRP) status during systemic treatment as the predictive marker for the response of subsequent nivolumab monotherapy in patients with refractory metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A total of 73 mRCC patients treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. Patients whose CRP did not exceed baseline value were defined as the CRP-control group and the others were defined as the CRP-progression group. The clinical impact of CRP-control on the efficacy of nivolumab was assessed. RESULTS: Twenty-four patients (33%) were categorized into the CRP-control group. The CRP-control group patients (median PFS not reached) had significantly longer PFS than the CRP-progression group (median PFS 11.9 months, 95% confidence interval, CI 4.1-19.8, p = 0.038). The CRP-control group had a tendency of longer OS from nivolumab initiation than the CRP-progression group (p = 0.071). By multivariate analysis, the on-treatment CRP-control was the independent predictive factor for PFS (hazard ratio HR 0.37, 95% CI 0.14-0.99, p = 0.047). CONCLUSION: The on-treatment CRP-control could be the predictive factor for the efficacy of nivolumab in refractory mRCC patients.

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