RESUMO
BACKGROUND: Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood. METHODS: A UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study. RESULTS: The in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression. CONCLUSIONS: DPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC.
Assuntos
Carcinoma de Células de Transição , Neoplasias Pancreáticas , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Regulação para Cima , Células Endoteliais , Prognóstico , Proteínas Musculares/genéticaRESUMO
PURPOSE: The purpose of this study is to evaluate the rates of pathological complete response (ypT0N0/X) and pathological response (ypT1N0/X or less) in patients with upper tract urothelial cancer who were treated with neo-adjuvant chemotherapy and to examine their impact on oncological outcomes. METHODS: This study is a multi-institutional retrospective analysis of patients with high-risk upper tract urothelial cancer who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021. Logistic regression analyses were used to investigate all clinical parameters for response after neoadjuvant chemotherapy. Cox proportional hazard models were performed to assess the effect of the response on the oncological outcomes. RESULTS: A total of 84 patients with UTUC who received neo-adjuvant chemotherapy were identified. Among them, 44 (52.4%) patients received cisplatin-based chemotherapy, and 22 (26.2%) patients had a carboplatin-based regimen. The pathological complete response rate was 11.6% (n = 10), and the pathological response rate was 42.9% (n = 36). Multifocal tumors or tumors larger than 3 cm significantly reduced the odds of pathological response. In the multivariable Cox proportional hazard model, pathological response was independently associated with better overall survival (HR 0.38, p = 0.024), cancer-specific survival (HR 0.24, p = 0.033), and recurrence-free survival (HR 0.17, p = 0.001), but it was not associated with bladder recurrence-free survival (HR 0.84, p = 0.69). CONCLUSION: Pathological response after neo-adjuvant chemotherapy and radical nephroureterectomy is strongly associated with patient survival and recurrence, and it might be a good surrogate for evaluating the efficacy of neo-adjuvant chemotherapy in the future.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Terapia Neoadjuvante , Nefroureterectomia , Estudos RetrospectivosRESUMO
BACKGROUND: to assess the efficacy of comprehensive geriatric assessment (CGA) for preventing treatment-related toxicity in older people undergoing non-surgical cancer therapies. METHODS: MEDLINE, EMBASE and Cochrane library databases were searched from inception till January 2022 to identify randomised controlled trials (RCTs) on the incidence of toxicity measured by the Common Terminology Criteria for Adverse Events (primary outcome) and that of therapeutic modifications, early treatment discontinuation, progression-free survival, overall survival and hospitalisation (secondary outcomes). RESULTS: analysis of six RCTs published from 2016 to 2021 recruiting 2,126 participants (median age: 71-77) who received chemotherapy as the major therapeutic approach revealed 51.7% and 64.7% of Grade 3+ toxicity in the CGA and control (i.e. standard care) groups, respectively (RR = 0.81, 95% CI: 0.7-0.94, P = 0.005, I2 = 65%, certainty of evidence [COE]: moderate). There were no significant differences in the incidence of early treatment discontinuation (RR = 0.88, P = 0.47; I2 = 63%,1,408 participants, COE: low), initial reduction in treatment intensity (RR = 0.99, P = 0.94; I2 = 83%, 2055 participants, COE: low), treatment delay (RR = 1.06, P = 0.77, I2 = 0%, 309 participants, COE: moderate), hospitalisation (RR = 0.86, P = 0.39, I2 = 41%, 914 participants, COE: moderate), progression-free and overall survival with or without CGA. However, there was an association between CGA and a lower incidence of dose reduction during treatment (RR = 0.73, P < 0.00001, 956 participants, COE: moderate). CONCLUSIONS: our results demonstrated that comprehensive geriatric assessment may be associated with a lower incidence of treatment-related toxicity and dose reduction compared to standard care in older people receiving non-surgical cancer treatments. Further large-scale studies are warranted to support our findings.
Assuntos
Avaliação Geriátrica , Hospitalização , Idoso , HumanosRESUMO
BACKGROUND: Staghorn stones require surgical treatment to prevent serious complications. Multitract percutaneous nephrolithotomy (PNL) causes great renal parenchymal injury and blood loss. One-stage endoscopic combined intrarenal surgery (ECIRS) entails the combined use of antegrade nephroscope and retrograde flexible ureteroscope to clear the staghorn stone, which may overcome the limitations of multitract PNL. We aimed to compare the perioperative outcomes of mini ECIRS and multitract minimally invasive PNL in staghorn stone management. METHODS: This was a retrospective single-center study of patients with staghorn stones who underwent ECIRS (n = 17) or multitract minimally invasive PNL (n = 17) between January 2018 and September 2021. RESULTS: There was a significant between-group difference with respect to Guy's stone score. Stone size, stone burden (ECIRS group, 21.41 cm3; multitract minimally invasive PNL group, 20.88 cm3 [P = 0.94]), and degree of hydronephrosis were comparable in the two groups. There was no significant between-group difference with respect to one-step or final stone-free rates. The mean operative time was also not significantly different between the groups (ECIRS group, 140 min; multitract minimally invasive PNL group, 183 min [P = 0.63]). ECIRS was associated with significantly lesser postoperative pain (visual analog scale; ECIRS group: 0; multitract minimally invasive PNL group: 2.7 [P < 0.001]). Hemoglobin loss, postoperative blood transfusion rate, complications, and length of hospital stay were comparable in the two groups. CONCLUSION: Both mini ECIRS and multitract minimally invasive PNL were effective and safe for the management of renal staghorn stones with comparable operation time and stone-free rate, and complications. ECIRS was associated with less severe postoperative pain.
Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Cálculos Coraliformes , Humanos , Rim , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Nefrostomia Percutânea/métodos , Dor Pós-Operatória , Estudos Retrospectivos , Cálculos Coraliformes/cirurgia , Resultado do Tratamento , Ureteroscopia/métodosRESUMO
BACKGROUND: Kidney transplantation is the preferred renal replacement therapy for patients with end-stage renal disease, but the waiting list for kidneys continues to grow because of a shortage of donor organs. The reuse of transplanted kidneys would seem to be a good approach to expand the pool of available organs. Here, we describe the reuse of a kidney 9 years after the initial transplantation. At 4-year follow-up, the second recipient is showing good renal function. CASE PRESENTATION: In 2005, a kidney was transplanted from a 40-year-old man, who suffered brain death due to an intracranial hemorrhage, into a 45-year-old man. Nine years later, the recipient suffered a ruptured cerebral aneurysm, resulting in brain death. The kidney was re-transplanted into a 40-year-old man with diabetic nephropathy who had received hemodialysis for 5 years. During 4 years of follow-up, the graft has functioned well. CONCLUSIONS: This case demonstrates the successful regrafting of a transplanted kidney. We believe this is the longest period for reuse of kidney after initial transplantation. The outcome suggests that a well-functioning transplanted kidney can be reused years after transplantation.
Assuntos
Sobrevivência de Enxerto/fisiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Transplantados , Transplantes/fisiologia , Transplantes/transplante , Adulto , Seguimentos , Humanos , Falência Renal Crônica/diagnóstico , Transplante de Rim/tendências , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
PURPOSE: Renal cysts are typically a benign condition, and parapelvic cysts are a type of renal cyst that occur adjacent to the renal pelvis or renal sinus. Parapelvic cysts can increase the risk for injury to adjacent organs or urine leakage during laparoscopic surgery. Flexible ureteroscopes with laser assistance were used to make internal incisions in cysts. Perioperative outcomes of this method were compared with those of laparoscopic surgery. METHODS: Eight-three patients, who underwent surgical treatment for renal cysts at the authors' medical center between January 2019 and June 2022, were evaluated. Two patients were excluded because they originally opted for RIRS but subsequently converted to laparoscopic surgery. Patients were divided into 2 groups based on surgery type: laparoscopic; and RIRS for internal incision. Outcomes in both groups were analyzed. RESULTS: Of the 81 patients analyzed, 60 [74% (group 1)] underwent laparoscopic surgery and 21 [26% (group 2)] underwent RIRS for internal incision. The median operative durations for groups 1 and 2 were 87 and 56 min, respectively (p < 0.001). Relative to RIRS, laparoscopic surgery resulted in greater postoperative painkiller use (laparoscopic surgery versus [vs.] RIRS, 43% vs. 19%; p = 0.047). The median length of hospital stay was 2 and 1 days, respectively (p < 0.001). CONCLUSIONS: RIRS demonstrated several advantages over laparoscopic surgery for the internal incision of parapelvic cysts, including shorter operative duration, shorter hospital stay, and less postoperative pain control. These findings may guide the selection of appropriate surgical approaches for patients with renal cysts.
Assuntos
Cistos , Cálculos Renais , Doenças Renais Císticas , Neoplasias Renais , Laparoscopia , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Ureteroscópios , Pelve Renal/cirurgia , Doenças Renais Císticas/cirurgia , Neoplasias Renais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Renais/cirurgiaRESUMO
In this study, we performed all-atom long-timescale molecular dynamics simulations of phospholipid bilayers incorporating three different proportions of negatively charged lipids in the presence of K(+), Mg(2+), and Ca(2+) ions to systemically determine how membrane properties are affected by cations and lipid compositions. Our simulations revealed that the binding affinity of Ca(2+) ions with lipids is significantly stronger than that of K(+) and Mg(2+) ions, regardless of the composition of the lipid bilayer. The binding of Ca(2+) ions to the lipids resulted in bilayers having smaller lateral areas, greater thicknesses, greater order, and slower rotation of their lipid head groups, relative to those of corresponding K(+)- and Mg(2+)-containing systems. The Ca(2+) ions bind preferentially to the phosphate groups of the lipids. The complexes formed between the cations and the lipids further assembled to form various multiple-cation-centered clusters in the presence of anionic lipids and at higher ionic strength-most notably for Ca(2+). The formation of cation-lipid complexes and clusters dehydrated and neutralized the anionic lipids, creating a more-hydrophobic environment suitable for membrane aggregation. We propose that the formation of Ca(2+)-phospholipid clusters across apposed lipid bilayers can work as a "cation glue" to adhere apposed membranes together, providing an adequate configuration for stalk formation during membrane fusion.
Assuntos
Cátions/química , Bicamadas Lipídicas , Fusão de Membrana , Simulação de Dinâmica Molecular , Fosfolipídeos/química , Modelos Moleculares , Água/químicaRESUMO
Objective: Partial nephrectomy (PN) is one of the surgical treatment options for renal tumors. Therefore, the aim of this study was to compare the surgical outcomes of retroperitoneal PN for anterior and posterior tumors. Materials and Methods: This study enrolled 177 patients who had renal tumors that were detected on abdominal computed tomography and underwent PN between January 2017 and April 2021. Tumor position was defined by the anatomic avascular Brodel's line. Surgical outcomes were compared between approaches using the chi-squared Student's t-tests, logistic regression analysis, and stratification analysis. Results: Of the 177 patients, 97 (54.8%) patients had anterior renal tumors and 80 (45.2%) had posterior renal tumors. On comparing the surgical results between the two groups, the anterior group had higher levels of hemoglobin (Hb) reduction (-1.92 vs -1.54 g/dL, p = 0.0444), but the estimated blood loss showed no significant difference between the two groups (497.6 vs 433.2 mL, p = 0.4149). In addition, the alteration in estimated glomerular filtration rate at postoperative 1st day (p = 0.5616), 6th month (p = 0.5046), and at postoperative 1st year (p = 0.7085) was not significantly different between the two groups. Other surgical outcomes, such as blood transfusion rate, complications, and lengths of stay, also had no significant difference. Stratified analysis revealed the anterior renal tumors had a 3.76 times risk (p = 0.0186) than the posterior tumors for decreasing Hb >10% under laparoscopic PN. No postoperative gastrointestinal-related complications were reported. Conclusions: This study demonstrated retroperitoneal surgical access to renal tumors and revealed equivalent surgical outcomes for both anterior and posterior renal tumors. Moreover, anterior renal tumors had benefits under robotic PN for bleeding control. Retroperitoneal PN can be considered as a good approach for both anterior and posterior renal tumors with few intra-abdominal complications.
Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos , Espaço Retroperitoneal/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Taxa de Filtração GlomerularRESUMO
Introduction: Adrenal tumors are relatively common, and adrenalectomy is the third most common endocrine surgery. Patients with adrenal tumors were categorized into two groups for analysis: those with intermediate (4-6 cm, Group 1) and large (>6 cm, Group 2) tumors undergoing Retroperitoneal Laparoscopic Adrenalectomy (RLA). The primary outcome is to compare the surgical outcomes between these two groups. The secondary outcome involves analyzing the relationship between tumor characteristics and the incidence of adverse events. Methods: Data from 76 patients who underwent RLA for tumors of size ≥4 cm between 2005 and 2022 at a single tertiary referral center were analyzed retrospectively. Variables, including patients' age, hormone function, operation time, conversion to open approach, perioperative complications, and adverse surgical events (blood loss >500 cc, conversion to open approach, and perioperative complications), were assessed. Results: No significant differences were observed between the two groups in terms of functional and histopathologic analysis, gender distribution, functioning factors, perioperative complications, and estimated blood loss. However, patients in Group 2 were younger (median age 50, IQR: 40-57, P = 0.04), experienced longer operative times (median 175 min, IQR: 145-230 min, P = 0.005), and had a higher rate of conversion to open surgery (12%, P = 0.033). For every 1 cm increase in tumor size, the odds ratio for adverse surgical events increased by 1.58. Conclusions: RLA is a safe and feasible procedure for adrenal tumors larger than 6 cm. While intraoperative and postoperative complications are not significantly increased in either group, larger tumors increase surgery times and are more likely to require conversion to open surgery. Therefore, caution and preparedness for potential adverse events are recommended when dealing with larger tumors. A tumor size of 5.3 cm may serve as a guide for risk stratification and surgical planning in large adrenal tumor management.
RESUMO
BACKGROUND: The role of smoking in the prognosis of bladder cancer may significantly impact clinical management. It is also a considerable burden to Taiwan's economy and health of its citizens. OBJECTIVE: To search Taiwan's National Health Insurance Research Database to determine whether smoking affected overall and cancer-specific mortality of patients with bladder cancer. METHODS: We collected data on basic information, tumor stage, and comorbidities. Each smoking case was propensity score-matched by age, sex, and diagnosis year to one control individual among bladder cancer patients. The study comprised a never-smoke and an ever-smoke group, with each group including 4,728 patients after matching. We evaluated the association between smoking and mortalities in patients with bladder cancer. Cox proportional regression modeling was used to estimate hazard ratios (HRs) of overall and cancer-specific mortality rates. Stratified analysis was also performed to estimate risk ratios of overall and cancer-specific mortalities in bladder cancer patients with and without a history of smoking history among different subgroups. RESULTS: The overall and specific mortality ratio of patients who were ever smokers were 1.15-fold and 1.16-fold, respectively, compared with those of never smokers (overall: 95% confidence interval [CI], 1.06-1.26, Pâ=â0.0014; specific: 95% CI, 1.03-1. 03, Pâ=â0.0176). Patients with bladder cancer who smoked and had significantly higher overall and specific mortality rates were those with Charlson Comorbidity Index (CCI)≥3 (overall: Pâ=â0.0119; specific: Pâ=â0.0092), diabetes mellitus (DM; overall: Pâ=â0.0046; specific: Pâ=â0.0419), and non-muscle-invasive bladder cancer (NMIBC; overall: Pâ=â0.0038; specific: Pâ=â0.0014). CONCLUSIONS: Overall and specific mortality rates were significantly higher in the ever-smoke group than in the never-smoke group. The ever-smoke group with male sex, CCI≥3, DM, and NMIBC had increased risks for overall and specific mortality.
RESUMO
Background: Urothelial carcinoma (UC) patients often bear clinical and genetic heterogeneity, which may differ in management and prognosis. Especially, patients with advanced/metastatic UC generally have a poor prognosis and survive for only few months. The Wnt/ß-catenin signaling is found to be highly activated in several cancers, including UC. However, accumulated evidence has shown discordance between the Wnt/ß-catenin signaling and UC carcinogenesis. Accordingly, we aim to get a better understanding of the molecular characterization of UC, focusing on the Wnt signaling, which may add value to guiding management more precisely. Patients and Methods: Clinical data and pathological features were retrospectively surveyed. The correlations of secreted Frizzled-related protein 2 (SFRP2) immunoexpression with clinicopathological features were analyzed by Pearson's chi-square test. The Kaplan-Meier method with a log-rank test was employed to plot survival curves. All significant features from the univariate analysis were incorporated into the Cox regression model for multivariate analysis. Results: Following data mining on a transcriptome dataset (GSE31684), we identified that 8 transcripts in relation to the Wnt signaling pathway (GO: 0016055) were significantly upregulated in advanced/metastatic bladder tumors. Among these transcripts, the SFRP2 level showed the most significant upregulation. Additionally, as SFRP2 is a putative Wnt inhibitor and may be expressed by stroma, we were interested in examining the immunoexpression and clinical relevance of stromal and tumoral SFRP2 in our urothelial carcinoma cohorts containing 295 urinary bladder UC (UBUC) and 340 upper urinary tract UC (UTUC) patients. We observed that high SFRP2 expression in stroma but not in tumors is significantly linked to aggressive UC features, including high tumor stage and histological grade, positive nodal metastasis, the presence of vascular and perineural invasion, and high mitotic activity in UBUC and UTUC. Moreover, high stromal SFRP2 expression significantly and independently predicted worse clinical outcomes in UBUC and UTUC. Utilizing bioinformatic analysis, we further noticed that stromal SFRP2 may link epithelial-mesenchymal transition (EMT) to UC progression. Conclusion: Collectively, these results imply that stromal SFRP2 may exert oncogenic function beyond its Wnt antagonistic ability, and stromal SFRP2 expression can provide prognostic and therapeutic implications for UC patients.
RESUMO
PURPOSE: In recent years, second-look transurethral resection of bladder tumors (TURBT) has been recommended for patients with stage T1 bladder cancer after the initial TURBT for restaging and deciding the subsequent treatment. However, we believe that second-look TURBT has therapeutic benefits, such as low incidence of recurrence and progression. Therefore, we compare the differences in long-term outcome between patients who did and did not accept second-look TURBT for stage T1 bladder cancer. METHODS: We assessed 504 patients diagnosed with urothelial carcinoma who underwent initial TURBT between January 2012 and December 2016 at a single medical center; of these patients, 177 were diagnosed with T1 bladder cancer during the initial TURBT, and we excluded no muscle from the specimen in the initial TURBT. The patients were categorized into groups 1 and 2 based on the acceptance of second-look TURBT, which was performed within 4-14 weeks after the initial TURBT. Group 1 underwent second-look TURBT, but group 2 did not. Both groups were followed-up for recurrence-free survival (RFS) and progression-free survival (PFS), and the risk factors for recurrence and progression were analyzed. RESULTS: In total, 93 (52.5%) patients in group 1 underwent second-look TURBT, and 84 (47.5%) in group 2 did not. The 2-year RFS rates were 74.6% and 60.0% and the PFS rates were 91.2% and 87.5% in groups 1 and 2, respectively. CONCLUSION: This study demonstrated higher recurrence-free and progression-free survival rates for patients who underwent second-look TURBT. This result emphasizes the importance of second-look TURBT in stage T1 bladder cancer not only for restaging but also for therapeutic benefit.
Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Reoperação , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Uretra , Neoplasias da Bexiga Urinária/patologiaRESUMO
The phytochemicals in fruits have been shown to be major bioactive compounds with regard to health benefits. Bacaba (Oenocarpus bacaba Mart.) is a native palm fruit from the Brazilian savannah and Amazon rainforest that plays an important role in the diet of rural communities and is also a source of income for poor people. This paper reports the characterization and analyses of phenolics from bacaba fruit extract. The total phenolic content of bacaba fruit amounted to 1759.27 ± 1.01 mg GAE/100 g, the flavonoid content was 1134.32 ± 0.03 mg CTE/100 g, and the anthocyanin content was 34.69 ± 0.00 mg cyn-3-glc/100 g. The antioxidant activity was evaluated through different assays [ORAC, FRAP, DPPH, TEAC, and cellular antioxidant assay (CAA) assays] and revealed a significant antioxidant capacity for bacaba in comparison to the data available in the literature. The assignment of the phenolic compounds using HPLC-DAD-MS(n) was based on the evaluation of their UV-vis absorption maxima (λ(max)) and mass spectral analyses, and 14 compounds were tentatively identified. The results suggest that bacaba fruits are a promising source of phenolics.