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1.
BMC Cancer ; 24(1): 247, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388388

RESUMO

BACKGROUND: Limited information is available for guiding the management of upper urinary tract (UUT) urothelial carcinoma with squamous differentiation (UC-SqD). We did not even know about the difference between pure urothelial carcinoma (UC) and UC-SqD in the UUT regardless of treatment policy and prognosis. Instead of direct comparisons against each other, we included the third UUT malignancy, squamous cell carcinoma (SCC). This three-way-race model allows us to more clearly demonstrate the impact of squamous cell transformation on patient outcomes in UUT malignancy. METHODS: We retrospectively analysed 327 patients with UC, UC-SqD, or SCC who underwent radical nephroureterectomy with bladder cuff excision (RNU) at Taichung Veterans General Hospital, Taichung, Taiwan, between January 2006 and December 2013. A Kaplan-Meier survival analysis was used to evaluate the relationship between patient outcomes and histology. Multivariate Cox proportional hazards modelling was also used to predict patient prognoses. RESULTS: The five-year postoperative cancer-specific survival (CSS) rates were 83.6% (UC), 74.4% (UC-SqD), and 55.6% (SCC), and the 5-year recurrence-free survival (RFS) rates were 87.7% (UC), 61.5% (UC-SqD), and 51.9% (SCC). UC patients had significantly better 5-year RFS than UC-SqD and SCC patients (P = 0.001 and P < 0.0001, respectively). Patients with pure UC had significantly better 5-year CSS than SCC patients (P = 0.0045). SCC or UC-SqD did not independently predict disease-specific mortality (HR 0.999, p = 0.999; HR 0.775, p = 0.632, respectively) or disease recurrence compared to pure UC (HR 2.934, p = 0.239; HR 1.422, p = 0.525, respectively). Age, lymphovascular invasion (LVI), and lymph node (LN) status independently predicted CSS, while pathological tumour stage, LN status, and LVI predicted RFS. CONCLUSIONS: SCC and UC-SqD are not independent predictors of survival outcomes in patients with UUT tumours. However, they are associated with other worse prognostic factors. Hence, different treatments are needed for these two conditions, especially for SCC.


Assuntos
Carcinoma de Células Escamosas , Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Nefroureterectomia , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Neoplasias Ureterais/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias Urológicas/cirurgia , Neoplasias Urológicas/patologia , Células Epiteliais/patologia , Carcinoma de Células Escamosas/cirurgia
2.
Clin Transplant ; 37(10): e15047, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37306943

RESUMO

BACKGROUND: The incidence of malignancies after successful kidney transplantation has historically been higher than in the general population, with adverse impact on clinical outcomes. However, uncertainty remains as to which cancers occur at what time points after kidney transplantation. METHODS: We conducted a longitudinal cohort study to investigate the temporal trends and topographic patterns of de novo malignancies to optimize surveillance protocols and improve transplant outcome in renal transplant recipients. Measurement of death and cancer events was performed to calculate the cumulative risk of events of interest. RESULTS: Between 2000 and 2013, 3169 renal transplant recipients were retrospectively screened; 3035 (96%) of them met eligibility criteria and were evaluated with a follow-up of 27612 person-years. There was suboptimal overall survival and malignancy-free survival in renal transplant recipients compared to reference groups (HR: 1.65; 95% CI: 1.50-1.82; p < .001; HR: 2.33; 95% CI: 2.04-2.66; p < .001, respectively). Among renal transplant recipients, urological malignancies were predominant (57.5%), followed by digestive tract malignancies (21.4%). The cancer risks of the urinary bladder and upper urinary tract were lower in male subjects (HR: .48; 95% CI: .33-.72; p < .001; HR: .34; 95% CI: .20-.59; p < .001, respectively). The temporal trends of urological malignancies among renal transplant recipients were expressed in a bimodal pattern, with M-shaped peaks at 3 and 9 years, with gender disparity. CONCLUSIONS: In renal transplant recipients, cancer occurrences are shown as M-shaped twin peaks. Our study highlights that specific customized 'targeted' strategies for cancer surveillance programs are required to optimize posttransplant care.


Assuntos
Transplante de Rim , Neoplasias , Neoplasias Urológicas , Humanos , Masculino , Transplante de Rim/efeitos adversos , Estudos Longitudinais , Estudos Retrospectivos , Neoplasias/epidemiologia , Neoplasias/etiologia , Estudos de Coortes , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/etiologia , Incidência , Transplantados , Fatores de Risco
3.
Int J Med Sci ; 20(7): 969-975, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324196

RESUMO

The downregulation of WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the tumorigenesis and poor prognosis of various cancers. In this study, we investigated the associations between the polymorphisms of WWOX, clinicopathologic features of prostate cancer (PCa), and risk of postoperative biochemical recurrence (BCR). We evaluated the effects of five single-nucleotide polymorphisms (SNPs) of WWOX on the clinicopathologic features of 578 patients with PCa. The risk of postoperative BCR was 2.053-fold higher in patients carrying at least one "A" allele in WWOX rs12918952 than in those with homozygous G/G. Furthermore, patients with at least one polymorphic "T" allele in WWOX rs11545028 had an elevated (1.504-fold) risk of PCa with seminal vesicle invasion. In patients with postoperative BCR, the risks of an advanced Gleason grade and clinical metastasis were 3.317- and 5.259-fold higher in patients carrying at least one "G" allele in WWOX rs3764340 than in other patients. Our findings indicate the WWOX SNPs are significantly associated with highly aggressive pathologic features of PCa and an elevated risk of post-RP biochemical recurrence.


Assuntos
Neoplasias da Próstata , Glândulas Seminais , Masculino , Humanos , Oxidorredutase com Domínios WW/genética , Glândulas Seminais/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Próstata/patologia , Prostatectomia , Antígeno Prostático Específico , Recidiva Local de Neoplasia/patologia , Proteínas Supressoras de Tumor/genética
4.
J Cell Physiol ; 237(12): 4517-4530, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36250981

RESUMO

Golgi apparatus (GA) and centrosome reposition toward cell leading end during directional cell migration in a coupling way, thereby determining cell polarity by transporting essential factors to the proximal plasma membrane. The study provides mechanistic insights into how GA repositioning (GR) is regulated, and how GR and centrosome repositioning (CR) are coupled. Our previous published works reveals that PRMT5 methylates HURP at R122 and the HURP m122 inhibits GR and cell migration by stabilizing GA-associated acetyl-tubulin and then rigidifying GA. The current study further shows that the demethylase JMJD6-guided demethylation of HURP at R122 promotes GR and cell migration. The HURP methylation mimicking mutant 122 F blocks JMJD6-induced GR and cell migration, suggesting JMJD6 relays GR stimulating signal to HURP. Mechanistic studies reveal that the HURP methylation deficiency mutant 122 K promotes GR through NF-κB-induced CR and subsequently CR-dependent Cdc42 upregulation, where Cdc42 couples CR to GR. Taken together, HURP methylation statuses provide a unique opportunity to understand how GR is regulated, and the GA intrinsic mechanism controlling Golgi rigidity and the GA extrinsic mechanism involving NF-κB-CR-Cdc42 cascade collectively dictate GR.


Assuntos
Movimento Celular , Centrossomo , Complexo de Golgi , Histona Desmetilases com o Domínio Jumonji , NF-kappa B , Proteína cdc42 de Ligação ao GTP , Centrossomo/metabolismo , Complexo de Golgi/metabolismo , NF-kappa B/metabolismo , Tubulina (Proteína)/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo
5.
Cancer Treat Res ; 183: 201-223, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35551661

RESUMO

Immunotherapy, the 5th pillar of cancer care after surgery, radiotherapy, cytotoxic chemotherapy, and precision therapy (molecular targeted therapy), is revolutionizing the standard of care in certain patients with genitourinary malignancies. As modest clinical benefits of IL-2 for metastatic renal cell carcinoma and Bacillus Calmette-Guerin therapy for early-stage bladder cancers in the past years, immune checkpoint inhibitors therapies demonstrate meaningful survival benefit and durable clinical response in renal cell carcinoma, urothelial carcinoma, and some prostate cancer. Despite best efforts, the benefits are limited to a minority of unselected patients due to the complexities of biomarker development. Now come the next hurdles: figuring out which patients best respond to immune checkpoint inhibitors and which patients won't respond to immune checkpoint inhibitors? How best to approach immune checkpoint inhibitors therapies to extend/maximize the treatment response as long as possible? How to overcome therapeutic resistance by specific concurrent immunomodulators or targeted therapy or chemotherapy? The role of immune checkpoint inhibitors in combination or sequencing with chemotherapy or other targeted therapies or other immunomodulating therapeutics in the early disease, neoadjuvant, adjuvant, and metastatic setting is actively under exploration. Ideal strategy for cancer care is to provide not just more time, but more quality time: there remain unmet needs for novel therapies that exploit molecular or genetic pathways to extend survival without compromising health-related quality of life for patients with advanced genitourinary malignancies. Further research is needed to discover new therapeutic strategies, and validate efficacy and effectiveness in real-world settings.


Assuntos
Carcinoma de Células Renais , Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Fatores Imunológicos , Imunoterapia , Masculino , Qualidade de Vida
6.
BMC Surg ; 22(1): 293, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902891

RESUMO

BACKGROUND: Malignant melanotic nerve sheath tumor (MMNST), formerly called melanotic schwannoma, is a rare tumor of neural crest derivation which most frequently arises from the region of spinal or autonomic nerves near the midline. Recent studies have reported malignant behavior of MMNST, and there still has no standard management guidelines. Intra-abdominal MMNST, which has never been reviewed as an entity, is even rarer. In this study, we present a rare case of a cystic MMNST arising from the para-aortic region and mimicking an intra-abdominal gastrointestinal stromal tumor (GIST), and review the literature regarding MMNSTs located in the abdominal cavity. CASE PRESENTATION: A 59-year-old female was incidentally found a tumor located in the left para-aortic area by non-contrast computed tomography. A Magnetic Resonance Imaging showed a cystic mass originated from the inferior mesenteric artery (IMA) territory. A GIST was initially diagnosed. The tumor was resected en bloc by laparoscopic surgery and was found between mesocolon and Gerota's fascia with blood supply of IMA. Grossly, dark brown materials were noted at the inner surface of the cystic wall. Microscopically, the tumor cells were melanin-containing, and no psammomatous bodies were present. Immunohistochemically, the tumor showed positivity for MART1, HMB45, collagen IV, and SOX10, and negativity for AE1/AE3. MMNST was favored over malignant melanoma, since the tumor was located near ganglia and had cells with less atypical cytology and a low mitotic rate, and subsequent adjuvant radiotherapy was performed. The patient was alive with no evidence of recurrent or metastatic disease 11 months after radiotherapy. CONCLUSIONS: Our review of abdominal MMNST cases showed a female predominance, with an average age of 54.8 years, and a trend toward being a larger tumor showing cystic or necrotic changes. Local recurrence and metastasis rate were reviewed, and both showed a low rate. Diagnosis of MMNST should combine all the available findings, and complete excision of the tumor should be performed, followed by long-term patient monitoring.


Assuntos
Neoplasias Encefálicas , Tumores do Estroma Gastrointestinal , Melanoma , Neoplasias de Bainha Neural , Neurilemoma , Neoplasias Cutâneas , Neoplasias de Tecidos Moles , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Neoplasias Cutâneas/patologia , Síndrome
7.
BJU Int ; 127(4): 412-417, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32745367

RESUMO

OBJECTIVE: To assess the effect of surgical experience on peri-operative, functional and oncological outcomes during the first 50 Retzius-sparing robot-assisted radical prostatectomy (RsRARP) cases performed by surgeons naïve to this novel approach. MATERIALS AND METHODS: We retrospectively evaluated the initial cases operated by 14 surgeons in 12 different international centres. Pre-, peri- and postoperative features of the first 50 patients operated by each surgeon in all the participating centres were collected. The effect of surgical experience on peri-operative, functional and oncological outcomes was firstly evaluated after stratification by level of surgical experience (initial [≤25 cases] and expert [>25 cases]) and after using locally weighted scatterplot smoothing to graphically explore the relationship between surgical experience and the outcomes of interest. RESULTS: We evaluated 626 patients. The median follow-up was 13 months in the initial group and 9 months in the expert group (P = 0.002). Preoperative features overlapped between the two groups. Shorter console time (140 vs 120 min; P = 0.001) and a trend towards lower complications rates (13 vs 5.5%; P = 0.038) were observed in the expert group. The relationship between surgical experience and console time, immediate urinary continence recovery and Clavien-Dindo grade ≥2 complications was linear, without reaching a plateau, after 50 cases. Conversely, a non-linear relationship was observed between surgical experience and positive surgical margins (PSMs). CONCLUSIONS: In this first report of a multicentre experience of RsRARP during the learning curve, we found that console time, immediate urinary continence recovery and postoperative complications are optimal from the beginning and further quickly improve during the learning process, while PSM rates did not clearly improve over the first 50 cases.


Assuntos
Curva de Aprendizado , Tratamentos com Preservação do Órgão/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
8.
Int J Med Sci ; 16(11): 1424-1429, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673232

RESUMO

Down-regulation of Growth arrest-specific 5 (GAS5) is correlated with enhanced cell proliferation and poorer prognosis of prostate cancer. We aimed to investigate the effect of variant rs145204276 of GAS5 on the prostate cancer susceptibility and clinicopathologic characteristics. In this study, 579 prostate cancer patients who underwent robot-assisted radical prostatectomy and 579 healthy controls were included. The frequency of the allele del of rs145204276 were compared between the patients and the controls to evaluate the impact of tumor susceptibility and the correlation of clinicopathological variables. The results shown that patients who carries genotype ins/del or del/del at SNP rs145204276 showed decreased risk of pathological lymph node metastasis disease (OR=0.545, p=0.043) and risk of seminal vesicle invasion (OR=0.632, p=0.022) comparing to with genotype ins/ins. In the subgroup analysis of age, more significant risk reduction effects were noted over lymph node metastasis disease (OR=0.426, p=0.032) and lymphovascular invasion (OR=0.521, p=0.025). In conclusion, the rs145204276 polymorphic genotype of GAS5 can predict the risk of lymph node metastasis. This is the first study to report the correlation between GAS5 gene polymorphism and prostate cancer prognosis.


Assuntos
Predisposição Genética para Doença , Metástase Linfática/genética , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , Alelos , Proliferação de Células/genética , Estudos de Associação Genética , Genótipo , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Prognóstico , Regiões Promotoras Genéticas , Prostatectomia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Fatores de Risco
9.
Int J Mol Sci ; 20(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395805

RESUMO

Cyclin-dependent kinase 5 (CDK5) is a unique member of the cyclin-dependent kinase family. CDK5 is activated by binding with its regulatory proteins, mainly p35, and its activation is essential in the development of the central nervous system (CNS) and neurodegeneration. Recently, it has been reported that CDK5 plays important roles in regulating various biological and pathological processes, including cancer progression. Concerning prostate cancer, the androgen receptor (AR) is majorly involved in tumorigenesis, while CDK5 can phosphorylate AR and promotes the proliferation of prostate cancer cells. Clinical evidence has also shown that the level of CDK5 is associated with the progression of prostate cancer. Interestingly, inhibition of CDK5 prevents prostate cancer cell growth, while drug-triggered CDK5 hyperactivation leads to apoptosis. The blocking of CDK5 activity by its small interfering RNAs (siRNA) or Roscovitine, a pan-CDK inhibitor, reduces the cellular AR protein level and triggers the death of prostate cancer cells. Thus, CDK5 plays a crucial role in the growth of prostate cancer cells, and AR regulation is one of the important pathways. In this review paper, we summarize the significant studies on CDK5-mediated regulation of prostate cancer cells. We propose that the CDK5-p35 complex might be an outstanding candidate as a diagnostic marker and potential target for prostate cancer treatment in the near future.


Assuntos
Quinase 5 Dependente de Ciclina/metabolismo , Neoplasias da Próstata/patologia , Androgênios/análise , Androgênios/metabolismo , Animais , Apoptose , Carcinogênese/metabolismo , Carcinogênese/patologia , Quinase 5 Dependente de Ciclina/análise , Humanos , Masculino , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia , Receptores Androgênicos/análise , Receptores Androgênicos/metabolismo , Fator de Transcrição STAT3/análise , Fator de Transcrição STAT3/metabolismo
10.
Int J Med Sci ; 15(14): 1731-1736, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588197

RESUMO

The high mobility group box 1 gene (HMGB1) plays a prominent role in cancer progression, angiogenesis, invasion, and metastasis. This study explored the effect of HMGB1 polymorphisms on clinicopathological characteristics of urothelial cell carcinoma (UCC). In total, 1293 participants (431 patients with UCC and 862 healthy controls) were recruited. Four single-nucleotide polymorphisms (SNPs) of HMGB1 (rs1412125, rs1360485, rs1045411, and rs2249825) were assessed using TaqMan real-time polymerase chain reaction assay. The results indicated that individuals carrying at least one T allele at rs1045411 had a lower risk of UCC than those with the wild-type allele [adjusted odds ratio = 0.722, 95% confidence interval (CI) = 0.565-0.924]. Furthermore, female patients with UCC carrying at least one T allele at rs1045411 were at a lower invasive tumor stage than those with the wild-type allele [odds ratio (OR) = 0.396, 95% CI = 0.169-0.929], similar to nonsmoking patients (OR = 0.607, 95% CI = 0.374-0.985). In conclusion, this is the first report on correlation between HMGB1 polymorphisms and UCC risk. Individuals carrying at least one T allele at rs1045411 are associated with a lower risk of UCC and a less invasive disease in women and nonsmokers.


Assuntos
Carcinoma de Células de Transição/genética , Predisposição Genética para Doença , Proteína HMGB1/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Alelos , Carcinoma de Células de Transição/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , não Fumantes , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
11.
Front Pharmacol ; 15: 1281654, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595923

RESUMO

Objectives: Immune checkpoint inhibitor (ICI) is an important treatment option for metastatic urothelial carcinoma (mUC) patients. A lot of clinical evidence proved the survival benefits of ICI, but cost-effectiveness of the treatment remains unclear. This study evaluates the cost-effectiveness of the ICIs treatment in different sequences among mUC patients. Methods: We retrospectively analyzed mUC patients who had been treated at our hospital between January 2016 and December 2020. These patients received chemotherapy with or without ICI treatment (Pembrolizumab, Atezolizumab, Nivolumab, Durvalumab, or Avelumab). The patients were divided into three different groups: receiving chemotherapy alone, receiving a combination of first-line ICI and chemotherapy (ICI combination therapy), and receiving chemotherapy as the first-line treatment followed by second-line ICI therapy (Subsequent ICI therapy). The primary endpoint was cost per life day, while lifetime medical costs and overall survival were also evaluated. Results: The 74 enrolled patients had a median age of 67.0 years, with 62.2% being male. Of these patients, 23 had received chemotherapy only, while the remaining patients had received combined therapy with ICI in either first-line or as subsequent agents (37 patients had ever received atezolizumab, 18 pembrolizumab, 1 Durvalumab, 1 Nivolumab, and 1 Avelumab separately.). Fifty-five patients (74.3%, 55/74) received cisplatin amongst all the patients who underwent chemotherapy. Median overall survival was 27.5 months (95% CI, 5.2-49.9) in the first-line ICI combination therapy group, and 8.9 months (95% CI, 7.1-10.8) in the chemotherapy only. Median overall survival for the subsequent ICI therapy group was not reached. The median lifetime cost after metastatic UC diagnosis was USD 31,221. The subsequent ICI therapy group had significantly higher costs when compared with the ICI combination therapy group (155.8 USD per day, [IQR 99.0 to 220.5] v 97.8 USD per day, [IQR 60.8 to 159.19], p = 0.026). Higher insurance reimbursement expenses for the subsequent ICI therapy group were observed when compared with the ICI combination therapy group. Conclusion: Our real-world data suggests that first line use of ICI combined with chemotherapy demonstrates better cost-effectiveness and similar survival outcomes for mUC patients, when compared with subsequent ICI therapy after chemotherapy.

12.
PLoS One ; 19(3): e0299102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547226

RESUMO

BACKGROUND: The role of upfront cytoreductive nephrectomy remains debatable in the present era of tyrosine kinase inhibitors and immune checkpoint inhibitors. Here, we aimed to evaluate the outcomes of metastatic renal cell carcinoma patients treated with upfront CN and modern systemic therapies. METHODS: Using the TriNetX network database, we identified patients, in the period from 2008 to 2022, who were diagnosed with metastatic renal cell carcinoma, receiving first-line systemic therapies with tyrosine kinase inhibitors or immune checkpoint inhibitors. Their overall survivals were evaluated using the Kaplan-Meier method as well as multivariable regressions. RESULTS: We identified 11,094 patients with metastatic renal cell carcinoma. Of them, 2,914 (43%) patients in the tyrosine kinase inhibitor cohort (n = 6,779), and 1,884 (43.7%) in the immune checkpoint inhibitors cohort (n = 4315) underwent upfront cytoreductive nephrectomy. Those receiving upfront cytoreductive nephrectomy showed survival advantages with either tyrosine kinase inhibitor (Hazard ratio 0.722, 95% Confidence interval 0.67-0.73, p<0.001) or immune checkpoint inhibitors (Hazard ratio 65.1, 95% Confidence interval 0.59-0.71, p<0.001). In multivariable analysis, upfront cytoreductive nephrectomy was a factor for improved OS in both cohorts: tyrosine kinase inhibitors (Hazard ratio 0.623, 95% Confidence interval 0.56-0.694, p<0.001) and immune checkpoint inhibitors cohort (Hazard ratio 0.688, 95% Confidence interval 0.607-0.779, p<0.001). CONCLUSIONS: Upfront cytoreductive nephrectomy was associated with an improved overall survival for patients with metastatic renal cell carcinoma receiving either first-line tyrosine kinase inhibitors or immune checkpoint inhibitors. Our results support a clinical role of upfront cytoreductive nephrectomy in the modern era.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Nefrectomia/métodos , Estudos Retrospectivos
13.
Anticancer Res ; 44(2): 543-553, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307563

RESUMO

BACKGROUND/AIM: Bladder cancer remains a significant global health concern, necessitating a deeper understanding of the molecular mechanisms underlying its progression. Cyclin-Dependent Kinase 5 (CDK5) has recently emerged as a potential player in bladder cancer pathogenesis. This study investigated the involvement of CDK5 in bladder cancer, emphasizing its potential as a therapeutic target. MATERIALS AND METHODS: The expression levels of CDK5 and p35 (CDK5 regulatory protein) and their roles in the tumor grade and malignancy of patient samples were evaluated using western blot analysis and immunohistochemistry. In addition, tumor cancer genome atlas (TCGA) was utilized to evaluate survival rate in patients with bladder cancer. We further confirmed the role of CDK5 with in vitro experiments using western blot analysis, immunocytochemistry, cell culture-based proliferation and migration assays. RESULTS: Higher CDK5 and p35 were associated with a higher tumor grade and poor survival rate in patients with bladder cancer. To confirm the role of CDK5 in vitro, we over-expressed CDK5 in bladder cancer cells. The results showed that the over-expression of CDK5 enhanced bladder cancer cell proliferation and migration. In addition, CDK5 inhibition by a pan-CDK inhibitor, Roscovitine (RV), significantly reduced proliferation of bladder cancer cells. Indeed, the migration and adhesion of bladder cancer cells were inhibited by RV treatment. CONCLUSION: CDK5 might play important roles in bladder cancer progression and be a potential diagnostic and therapeutic target in the near future.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Proliferação de Células , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Roscovitina , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
14.
Asian J Surg ; 47(1): 303-309, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37689515

RESUMO

BACKGROUND: An ideal technique for peritoneal dialysis (PD) catheter insertion should provide a long-term functioning catheter until permanent renal replacement therapy becomes available. We developed a technique using the nephroscope-assisted single-trocar approach in 2011. In this study, we report the outcomes, learning curve analysis and cost-effectiveness analysisof the nephroscopic approach compared with the traditional laparoscopic approach. METHOD: Between January 2005 and December 2020, we retrospectively reviewed 511 patients who received PD catheter insertions using the laparoscopic or nephroscopic approach. We compared the baseline characteristics of the patients, surgical outcomes, and complications of the two groups. We further analyzed the nephroscopic group to determine the cost-effectiveness analysis, learning curve and the complication frequency between the learning and mastery periods of the nephroscopic approach. RESULTS: A total of 208 patients underwent laparoscopic PD catheter insertion, whereas 303 patients received nephroscopic surgery. The median catheter survival in the nephroscopic group is significantly longer (43.1 vs. 60.5 months, p = 0.019). The incidence of peritonitis (29.3% vs.20.8%, p = 0.035) and exit site infection (12.5% vs. 6.6%, p = 0.019) were significantly lower in the nephroscopic group. The cost-effectiveness analysis showed a medical expense reduction of 16000 USD annually by using the nephroscopic technique. There was no difference in the frequency of surgical complications between the learning and mastery phases when examining the learning curve analysis for the nephroscopic technique. CONCLUSIONS: Compared with the traditional laparoscopic approach, the nephroscopic technique effectively prolonged catheter survival and reduces health care cost by reducing infectious complications. The low complication rate during the learning phase of surgery makes the procedure safe for patients and surgeons.


Assuntos
Falência Renal Crônica , Laparoscopia , Diálise Peritoneal , Humanos , Cateteres de Demora , Estudos Retrospectivos , Diálise Peritoneal/métodos , Laparoscopia/métodos , Instrumentos Cirúrgicos , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia
15.
Support Care Cancer ; 21(3): 907-11, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23262811

RESUMO

PURPOSE: The purpose of this study is to evaluate the efficacy of a protocol including topical heparin therapy for hand-foot skin reactions (HFSR) during multikinase (MKI) treatment. METHODS: We prospectively collected 26 patients who had HFSRs during treatment with the MKIs, sunitinib, sorafenib, or axitinib. The age distribution ranged from 46 to 87 years, with a mean of 66 years. The distribution of HFSR severity was 12 patients with grade 1, 12 with grade 2, and 2 with grade 3. A heparin-containing topical ointment treatment, combined with hand-foot shock absorbers and skin moisturizers, was used at the lesion sites. Changes in the grade of HFSR, MKI dosage, and interruptions of MKI therapy were recorded. RESULTS: The results showed that 66.7% of grade 1 patients were cured of disease, 83.3% of grade 2 patients had improved symptoms, and both grade 3 patients (100%) had improved symptoms and were downgraded to grade 2. Four (15.4%) patients required reduction of MKI dosage, but there were no treatment interruptions or dropouts. CONCLUSION: Our protocol is beneficial in promoting resolution of HFSRs induced by MKIs. Further validation in large control studies should be investigated.


Assuntos
Síndrome Mão-Pé/tratamento farmacológico , Heparina/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Axitinibe , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/patologia , Heparina/administração & dosagem , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Indazóis/uso terapêutico , Indóis/administração & dosagem , Indóis/efeitos adversos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Pomadas , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Estudos Prospectivos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Índice de Gravidade de Doença , Sorafenibe , Sunitinibe , Resultado do Tratamento
16.
Transplant Proc ; 55(7): 1581-1587, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37380588

RESUMO

BACKGROUND: Kidney transplantation is a treatment option for patients with end-stage renal disease (ESRD) who are infected with hepatitis B virus (HBV). However, the impact of nucleos(t)ide analogues usage on the clinical outcomes in HBV-infected ESRD patients undergoing kidney transplantation is not well understood. This study aimed to assess the outcomes of kidney transplant recipients with HBV infection using real-world data to provide insight into the disease course over time. METHODS: A nationwide retrospective longitudinal population-level cohort study was conducted using the National Health Insurance Research Database. The study evaluated patient and allograft survival and kidney-related and liver-related events and identified factors contributing to these events. RESULTS: Of the 4838 renal transplant recipients in the study, there were no significant differences in graft survival between the HBV-infected and non-infected groups (P = .244). However, the HBV-infected group had suboptimal patient survival compared to the non-infected group (hazard ratio [HR] for overall survival, 1.80; 95% CI 1.40-2.30; P < .001). Diabetes mellitus was associated with a higher re-dialysis rate (HR, 1.71; 95% CI, 1.38-2.12; P < .001) regarding kidney-associated events. For liver-associated events, HBV-infected status (HR, 9.40; 95% CI, 5.66-15.63; P < .001), and age >60 years (HR, 6.90; 95% CI, 3.14-15.19; P < .001) were associated with increased incidence of liver cancer. CONCLUSIONS: Hepatitis B-infected renal transplant recipients have comparable graft survival but inferior patient survival outcomes due to pre-existing diseases and increasing liver-related complications. The findings of this study can help optimize treatment strategies and improve long-term outcomes for this patient population.


Assuntos
Hepatite B , Falência Renal Crônica , Transplante de Rim , Humanos , Pessoa de Meia-Idade , Vírus da Hepatite B , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Diálise Renal , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Rim , Sobrevivência de Enxerto , Transplantados , Resultado do Tratamento
17.
Transplant Proc ; 55(10): 2429-2435, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37903695

RESUMO

BACKGROUND: The potential risks and benefits of kidney transplantation in patients with end-stage renal disease (ESRD) infected with hepatitis B virus (HBV) have been a subject of debate. This study aimed to provide real-world data on the relative risks of death and clinical outcomes associated with kidney transplantation in this context. METHODS: We conducted a longitudinal cohort study using the National Health Insurance Research Database from 1997 to 2013, extracting cohorts of patients who are HBV-infected ESRD. The main outcome measure was overall survival, whereas the secondary measure was the relative risk of death and survival benefit through propensity-score matching (1:1). RESULTS: Of the 4895 patients who are HBV-infected with ESRD, 172 renal transplant recipients were enrolled for analysis. There was a numeric trend towards higher overall survival rates in renal transplant recipients, although this was not statistically significant (P = .057). A significant survival benefit was observed in the renal transplant group if the follow-up was longer than one year (P = 0.007). The relative risks of death among renal transplant recipients were initially higher at 2.0 times that of patients on chronic dialysis, presenting in a hyperbolic pattern with equal risks at 462 days. The likelihood of survival became equal until 1649 days. CONCLUSIONS: Our study suggests that kidney transplantation may be a viable option for patients who are HBV-infected with ESRD, given the significant improvement in quality of life and reduction of death risks observed four to five years after successful transplantation. This real-world data can help clinicians make informed decisions regarding the management of ESRD in patients who are HBV-infected.


Assuntos
Falência Renal Crônica , Transplante de Rim , Humanos , Diálise Renal , Vírus da Hepatite B , Transplante de Rim/efeitos adversos , Estudos Longitudinais , Qualidade de Vida , Falência Renal Crônica/cirurgia , Análise de Sobrevida
18.
In Vivo ; 37(2): 786-793, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36881046

RESUMO

BACKGROUND/AIM: This study aimed to compare the prostate volume (PV) and prostate-specific antigen density (PSAD) obtained using the ellipsoid volume formula or segmentation methods on magnetic resonance imaging (MRI) and further predict prostate cancer (PCa). PATIENTS AND METHODS: Retrospectively, the enrolled patients underwent prostate MRI and had PSA levels between 4 and 10 ng/ml. The PV was measured with both the ellipsoid volume formula (PVe) and the segmentation method (PVs). The transitional zone volume (TZV) was measured with the segmentation method. The PSADe, PSADs, and PSAD_TZV were calculated. Bland-Altman plots were used to compare the agreements. ROC curve analysis was used to compare the diagnostic accuracies to predict PCa. The results were also compared between the PCa and the no-PCa groups, and among tumors with different locations and different Gleason scores (GS). RESULTS: Seventy-six of the 117 enrolled patients were classified into the PCa group. There were high agreements between PVs and PVe as well as between PSADs and PSADe, while several outliers were mainly due to post-transurethral resection of the prostate changes and irregular hyperplastic nodules. The diagnostic accuracy of PSADe (AUC: 0.732) was slightly higher than that of PSADs (AUC: 0.729) and PSAD_TZV (AUC: 0.715). The PSADe and PSADs were not different among different tumor locations but were higher in GS ≥7 lesions (both p=0.006). CONCLUSION: The segmentation method can be an alternative method to measure PV and calculate PSAD before prostate biopsy, particularly in post-transurethral resection of the prostate patients or those with irregular hyperplastic nodules.


Assuntos
Antígeno Prostático Específico , Ressecção Transuretral da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Estudos Retrospectivos , Hiperplasia , Imageamento por Ressonância Magnética
19.
Anticancer Res ; 43(4): 1699-1708, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36974775

RESUMO

BACKGROUND/AIM: To survey the safety and efficacy of percutaneous cryoablation for renal tumors under local anesthesia and pain control by using the -40°C lethal isotherm of the ice ball to cover the tumor margin as well as the coaxial cryoablation technique. PATIENTS AND METHODS: All procedures were performed between February 2014 and November 2021 with computed tomography (CT) guidance. All tumors were ablated by following the aforementioned plan, according to which tumor margins were covered by the -40°C lethal isotherm. Hydrodissection and coaxial cryoablation were performed in some cases to avoid organ injury and massive bleeding. 2% xylocaine was used for local anesthesia and 50 mg of pethidine (meperidine) was injected intramuscularly for pain control and sedation. The complications were evaluated and the Kaplan-Meier method was used to estimate local recurrence-free survival (LRFS). RESULTS: Sixty-five tumors [49 renal cell carcinomas (RCC) and 16 angiomyolipomas] were ablated in 55 patients (median Charlson Comorbidity Index=5.0). Local recurrence occurred in three of the 49 RCC cases. Two received a second cryoablation. LRFS at three and five years were both 91%. LRFS at three and five years reached 100% in tumors <3 cm. A large tumor (≥3 cm) was observed in the recurrence group. Hemorrhage was the most common complication (76.9%). Two patients who needed blood transfusion did not receive coaxial cryoablation. Three (4.6%) major complications (Clavien-Dindo grade ≥3) occurred. CONCLUSION: By using -40°C as the pre-plan tumor coverage, with the aid of coaxial cryoablation and multiplanar reconstruction method, CT-guided percutaneous renal cryoablation under local anesthesia is a safe and effective procedure in patients with many comorbidities.


Assuntos
Carcinoma de Células Renais , Criocirurgia , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Criocirurgia/efeitos adversos , Criocirurgia/métodos , Anestesia Local , Taiwan , Estudos de Viabilidade , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Tomografia Computadorizada por Raios X/métodos , Dor/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
20.
PLoS One ; 18(3): e0282745, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36893185

RESUMO

OBJECTIVES: Transurethral resection of prostate (TURP) and laser prostate surgery are common surgeries for benign prostate hyperplasia (BPH). We conducted an investigation using hospital database to evaluate the clinical factors associated with post-operative usage of alpha-blockers and antispasmodics. METHODS: This study was conducted using retrospective clinical data from the hospital database, which contained newly diagnosed BPH patients between January 2007 and December 2012 who subsequently received prostate surgery. The study end-point was the use of alpha-blockers or antispasmodics for at least 3 months duration after 1 month of surgery. The exclusion criteria was prostate cancer diagnosed before or after the surgery, recent transurethral surgeries, history of open prostatectomy, and history of spinal cord injury. Clinical parameters, including age, body mass index, preoperative prostate specific antigen value, comorbidities, preoperative usage of alpha-blockers, anstispasmodics and 5-alpha reductase inhibitors, surgical methods, resected prostate volume ratios, and preoperative urine flow test results, were evaluated. RESULTS: A total of 250 patients receiving prostate surgery in the database and confirmed pathologically benign were included. There was significant association between chronic kidney disease (CKD) and the usage of alpha-blockers after prostate surgery (OR = 1.93, 95% CI 1.04-3.56, p = 0.036). Postoperative antispasmodics usage was significantly associated with preoperative usage of antispasmodics (OR = 2.33, 95% CI 1.02-5.36, p = 0.046) and resected prostate volume ratio (OR = 0.12, 95% CI 0.02-0.63, p = 0.013). CONCLUSIONS: BPH patients with underlying CKD were more likely to require alpha-blockers after surgery. In the meantime, BPH patients who required antispasmodics before surgery and who received lower prostate volume resection ratio were more liable to antispasmodics after prostate surgery.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Próstata/cirurgia , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/complicações , Ressecção Transuretral da Próstata/métodos , Parassimpatolíticos , Estudos Retrospectivos , Antagonistas Adrenérgicos alfa/uso terapêutico , Fatores de Risco , Resultado do Tratamento
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