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Tumor-infiltrating lymphocytes (TILs) have been extensively explored as prognostic biomarkers and cellular immunotherapy methods in cancer patients. However, the prognostic significance of TILs in bladder cancer remains unresolved. We evaluated the prognostic effect of TILs in bladder cancer patients. Sixty-four bladder cancer patients who underwent surgical resection between 2018 and 2020 in Zhejiang Provincial People's Hospital were analyzed in this study. Immunohistochemistry was used to evaluate CD3, CD4, CD8, and FoxP3 expression on TILs in the invasive margin of tumor tissue, and the presence of TIL subsets was correlated with the disease-free survival (DFS) of bladder cancer patients. The relationship between clinical-pathological features and DFS were analyzed. A high level of CD3 + TILs (CD3 high TILs) ( P = 0.027) or negative expression of FoxP3 TILs (FoxP3 - TILs) ( P = 0.016) was significantly related to better DFS in bladder cancer patients. Those with CD3 high FoxP3 - TILs had the best prognosis compared to those with CD3 high FoxP3 + TILs or CD3 low FoxP3 - TILs ( P = 0.0035). Advanced age [HR 4.57, (1.86-11.25); P = 0.001], CD3 low TILs [HR 0.21, (0.06-0.71); P = 0.012], CD8 low TILs [HR 0.34, (0.12-0.94); P = 0.039], and FoxP3 + TILs [HR 10.11 (1.96-52.27); P = 0.006] in the invasive margin were associated with a worse prognosis (DFS) by multivariate analysis. In conclusion, we demonstrated that CD3 high , FoxP3 - , and CD3 high FoxP3 - TILs in the invasive margin were significantly associated with better DFS. CD8 high and CD4 high TILs in the invasive margin tended to predict better DFS in bladder cancer. Patients with CD4 high CD8 high TILs in the invasive margin were likely to have a better prognosis.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Bexiga Urinária , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/metabolismo , Linfócitos T CD8-PositivosRESUMO
BACKGROUND: Urinary bladder lymphangioma is a rare and benign lesion that is often causes symptoms related to irritation and urinary tract obstruction. Because a lymphangioma may resemble a true neoplasm of the urinary bladder clinically, the lesion must be removed for accurate histologic diagnosis and to rule out malignancy. CASE PRESENTATION: We present a case of a 40-year-old female who was evaluated for painless gross hematuria. Clinical and diagnostic work up revealed a sharply defined mass involving the wall and bulging into the cavity on the dome of the bladder. Partial cystectomy was performed and histologic findings were compatible with cavernous lymphangioma. The symptom of hematuria relieved after the procedure and the patient was in good status without evidence of recurrence by cystoscopy at follow-up 6 months later. CONCLUSIONS: Lymphangioma of the urinary bladder is treated with surgical excision and seems to have no recurrence once completely resected, but long-time follow-up may be needed.
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Linfangioma/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Cistectomia , Feminino , Hematúria/etiologia , Humanos , Linfangioma/diagnóstico por imagem , Linfangioma/patologia , Linfangioma/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
The objective of this study was to investigate the expression of vesicular amine transporter 1 (VAT1) in hepatocellular carcinoma (HCC) and its prognostic value and to analyze the relationship between VAT1 expression and clinicopathological features of HCC. First, several public databases, including Ualcan, GEPIA, and Oncomine, were used to analyze the expression of VAT1 in HCC and normal liver tissue. Next, 330 HCC and 190 normal liver samples were stained by immunohistochemistry and scored. Finally, we evaluated the clinical significance of VAT1 as a prognostic factor according to the clinicopathological characteristics. We observed that the expression level of VAT1 in HCC samples was significantly higher than that in normal liver tissues, and the high expression of VAT1 protein in HCC was significantly correlated with patient age, tumor size, number of tumors, and vascular metastasis (p<0.05). The average survival time of HCC patients with high expression of VAT1 was significantly lower than that of patients with low expression of VAT1. Further analysis demonstrated that VAT1 expression was significantly correlated with the length of overall survival in HCC patients. In conclusion, VAT1 may have an essential function in the progression of HCC, and the level of its expression may effectively predict the invasion and prognosis of HCC. Moreover, the combination of information contained in public databases and the results of the analysis of clinical samples can help us to understand better the mechanism of action of molecular oncogenes in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Humanos , Imuno-Histoquímica , PrognósticoRESUMO
CORRECTION: After publication of this work [1] it was noticed the author - Jie Wang's name was in the wrong order. The original article was corrected. The publisher apologises for this error.
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BACKGROUND: Renal artery aneurysm (RAA) is rare and its incidence in the general population remains elusive. There have been few reports on the repair of multiple aneurysms conducted with the Da Vinci robot-assisted surgical platform (Intuitive Surgical Inc., Sunnyvale, CA, USA), especially for those located in renal artery primary bifurcations. CASE PRESENTATION: We report our experience in the surgical management of two expanding right-sided RAAs in a 64-year-old man using a robot-assisted laparoscopic approach. Two aneurysms were located in renal artery primary bifurcations, whose diameter was 1.8 and 1.2 cm. The aneurysms were resected and the renal artery branch reconstructed by in situ arteriorrhaphy. The operation lasted for 2 h and 35 min with a warm ischemia time of 26 min and estimated blood loss of 150 ml. The hospital stay was 6 days. The computed tomography (CT) scan performed 2 months after the surgery showed resolution of the aneurysms. Additionally, split renal function indicated the preservation of right renal function in the follow-up period. CONCLUSIONS: The robot-assisted laparoscopic procedure is a safe and effective surgical technique, which may be considered as an alternative to open surgery for complex multiple RAAs in the future.
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Aneurisma/cirurgia , Gerenciamento Clínico , Laparoscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Artéria Renal/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Aneurisma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Renal/diagnóstico por imagem , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
OBJECTIVE: To induce hypospadias in male rat offspring by maternal exposure to di-n-butyl phthalate (DBP) during late pregnancy and further investigate its mechanisms. METHODS: We randomly divided 20 pregnant rats into a DBP exposure and a control group, the former treated intragastrically with DBP while the latter with soybean oil at 750 mg per kilogram of the body weight per day from gestation days (GD) 14 to 18. On postnatal day (PND) 1, we recorded the incidence rate of hypospadias and observed the histopathological changes in the genital tubercle of the hypospadiac rats. We also measured the level of serum testosterone (T) by radioimmunoassay and determined the mRNA and protein expressions of the androgen receptor (AR), sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4) and fibroblast growth factor 8 (Fgf8) in the genital tubercle by real-time PCR and Western blot. RESULTS: No hypospadiac male rats were found in the control group. The incidence rate of hypospadias in male offspring was 43.6% in the DBP-treatment group. Histological analysis confirmed hypospadiac malformation. The serum testosterone concentration was decreased in the hypospadiac male rats as compared with the controls (ï¼»0.49 ± 0.05ï¼½ vs ï¼»1.12 ± 0.05ï¼½ ng/ml, P <0.05). The mRNA expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle were significantly lower in the hypospadiac male rats than in the controls (AR: 0.50 ± 0.05 vs 1.00 ± 0.12, P <0.05; Shh: 0.65 ± 0.07 vs 1.00 ± 0.15, P <0.05; Bmp4: 0.42 ± 0.05 vs 1.00 ± 0.13, P <0.05; Fgf8: 0.46 ± 0.04 vs 1.00 ± 0.12, P <0.05), and so were their protein expressions (AR: 0.34 ± 0.05 vs 1.00 ± 0.09, P <0.05; Shh: 0.51 ± 0.07 vs 1.00 ± 0.12, P <0.05; Bmp4: 0.43 ± 0.05 vs 1.00 ± 0.11, P <0.05; Fgf8: 0.57 ± 0.04 vs 1.00 ± 0.13, P <0.05). CONCLUSIONS: Maternal exposure to DBP during late pregnancy can induce hypospadias in the male rat offspring. DBP affects the development of the genital tubercle by reducing the serum T concentration and expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle, which might underlie the mechanism of DBP inducing hypospadias.
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Dibutilftalato/toxicidade , Hipospadia/induzido quimicamente , Exposição Materna , Plastificantes/toxicidade , Animais , Peso Corporal , Proteína Morfogenética Óssea 4/sangue , Feminino , Fator 8 de Crescimento de Fibroblasto/sangue , Proteínas Hedgehog/sangue , Hipospadia/sangue , Hipospadia/patologia , Masculino , Gravidez , RNA Mensageiro/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/sangue , Óleo de Soja , Testosterona/sangueRESUMO
Competing endogenous RNAs (ceRNAs) are transcripts that can regulate each other at post-transcription level by competing for shared miRNAs. CeRNA networks link the function of protein-coding mRNAs with that of non-coding RNAs such as microRNA, long non-coding RNA, pseudogenic RNA and circular RNA. Given that any transcripts harbouring miRNA response element can theoretically function as ceRNAs, they may represent a widespread form of post-transcriptional regulation of gene expression in both physiology and pathology. CeRNA activity is influenced by multiple factors such as the abundance and subcellular localisation of ceRNA components, binding affinity of miRNAs to their sponges, RNA editing, RNA secondary structures and RNA-binding proteins. Aberrations in these factors may deregulate ceRNA networks and thus lead to human diseases including cancer. In this review, we introduce the mechanisms and molecular bases of ceRNA networks, discuss their roles in the pathogenesis of cancer as well as methods of predicting and validating ceRNA interplay. At last, we discuss the limitations of current ceRNA theory, propose possible directions and envision the possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets.
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Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias/genética , Regulação da Expressão Gênica , Humanos , RNA/metabolismo , RNA Circular , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Transcrição GênicaRESUMO
BACKGROUND: Cyclin D1 (CCND1) is critical in the transition of the cell cycle from the G1 to S phases, and unbalanced cell cycle regulation is a hallmark of carcinogenesis. Numerous epidemiological studies have evaluated the association between the CCND1 A870G polymorphism and the risk of prostate cancer (PCa). However, these studies have yielded conflicting results. METHODS: In the present study, the possible association above was assessed by a meta-analysis. Eligible articles were identified for the period up to July 2014. Pooled odds ratios (ORs) with 95% confidence intervals (95% CI) were appropriately derived from fixed effects or random effects models. RESULTS: A total of ten case-control studies, which included 3,820 cases and 3,825 controls, were identified. Overall, the allelic/genotypic association between the G870A polymorphism and prostate cancer was nonsignificant (OR = 1.045, 95% CI = 0.947 to 1.153 for A versus G, P = 0.380; OR = 1.088, 95% CI = 0.896 to 1.321 for AA versus GG, P = 0.393; OR = 1.044, 95% CI = 0.941 to 1.158 for GA versus GG, P = 0.414; OR = 1.053, 95% CI = 0.955 to 1.161 for the dominant model AA + GA versus GG, P = 0.303; OR = 1.072, 95% CI = 0.881 to 1.306 for the recessive model AA versus AA + GA, P = 0.486). Moreover, subgroup analyses according to ethnicity failed to demonstrate a significant association between this polymorphism and prostate cancer. In addition, we also performed a stratified analysis of cases with PCa metastasis, and the results supported the findings of no significant association between CCND1 A870G polymorphism and metastasis risk of PCa. CONCLUSIONS: Our results suggest that the CCND1 A870G polymorphism might not be a potential candidate for predicting prostate cancer risk, including metastasis risk.
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Ciclina D1/genética , Predisposição Genética para Doença , Polimorfismo Genético/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Humanos , Masculino , Prognóstico , Fatores de RiscoRESUMO
Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.
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Antígeno B7-H1 , Curcumina , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias da Bexiga Urinária , Animais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Curcumina/uso terapêutico , Curcumina/administração & dosagem , Camundongos , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Humanos , Linhagem Celular Tumoral , Feminino , Colite/induzido quimicamente , Colite/imunologia , Colite/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Sistemas de Liberação de Medicamentos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologiaRESUMO
PURPOSE: To compare the long-term clinical and oncologic outcomes of laparoscopic partial nephrectomy (LPN) and laparoscopic radical nephrectomy (LRN) in patients with renal cell carcinoma (RCC) > 4 cm. METHODS: We retrospectively reviewed the records of all patients who underwent LPN or LRN in our department from January 2012 to December 2017. Of the 151 patients who met the study selection criteria, 54 received LPN, and 97 received LRN. After propensity-score matching, 51 matched pairs were further analyzed. Data on patients' surgical data, complications, histologic data, renal function, and survival outcomes were collected and analyzed. RESULTS: Compared with the LRN group, the LPN group had a longer operative time (135 min vs. 102.5 min, p = 0.001), larger intraoperative bleeding (150 ml vs. 50 ml, p < 0.001), and required longer stays in hospital (8 days vs. 6 days, p < 0.001); however, the level of ECT-GFR was superior at 3, 6, and 12 months (all p < 0.001). Similarly, a greater number of LRN patients developed CKD compared with LPN until postoperative 12 months (58.8% vs. 19.6%, p < 0.001). In patients with preoperative CKD, LPN may delay the progression of the CKD stage and even improve it when compared to LRN treatment. There were no significant differences between the two groups for OS, CSS, MFS, and PFS (p = 0.06, p = 0.30, p = 0.90, p = 0.31, respectively). The surgical method may not be a risk factor for long-term survival prognosis. CONCLUSION: LPN preserves renal function better than LRN and has the potential value of significantly reducing the risk of postoperative CKD, but the long-term survival prognosis of patients is comparable.
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Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Insuficiência Renal Crônica , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Estudos Retrospectivos , Resultado do Tratamento , Laparoscopia/métodos , Nefrectomia/métodos , Insuficiência Renal Crônica/cirurgiaRESUMO
PURPOSE: To determine whether di-n-butyl phthalate (DBP) promotes the occurrence of bladder cancer (BCa) and explore the action of DBP acts on BCa cells at the cellular and molecular levels. METHODS: MTT and Transwell assays were used to investigate the tumorigenic actions of DBP on BCa cells. Second-generation sequencing was used to identify differences in gene expression before and after DBP treatment. Differential gene expression was verified by q-PCR and analyzed using bioinformatics. Cells were transfected to overexpress genes of interest and proliferation and migration were measured using MTT and Transwell assays, respectively. RESULTS: DBP treatment stimulated both proliferation and invasion in BCa cells. Second-generation sequencing identified differences in the expression of FOSB, JUND, ATP6V1C2, and RHOQ before and after DBP treatment. FOSB expression was confirmed by q-PCR and bioinformatic analyses. FOSB overexpression increased both proliferation and invasion in BCa cells. CONCLUSION: DBP promoted BCa tumorigenesis by inducing changes in gene expression.
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Dibutilftalato , Neoplasias da Bexiga Urinária , Humanos , Dibutilftalato/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Proliferação de Células , CarcinogêneseRESUMO
The purpose of this study was to investigate the predictors of metastatic patterns of upper tract urothelial carcinoma (UTUC) and to analyze the surgical outcomes of different metastatic patterns of UTUC. Data on patients with UTUC from 2010 to 2017 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier analysis was applied to compare the patients' survival distributions. Univariate and multivariate logistic regression was used to assess the specific predictors of site-specific metastases, while competitive risk regression was applied to estimate the predictors of cancer-specific mortality in patients with metastases. A total of 9,436 patients were enrolled from the SEER database, of which 1,255 patients had distant metastases. Lung metastasis (42.5%) was most common and patients with single distant lymph node metastasis had a better prognosis. Clinical N stage (N1, N2, N3) was the strongest predictors of the site specific metastatic sites. Renal pelvis carcinoma was more prone to develop lung metastases (OR = 1.67, P < 0.01). Resection of the primary tumor site is beneficial for the prognosis of patients with metastatic UTUC, whether local tumor resection (HR = 0.72, P < 0.01) or nephroureterectomy (HR = 0.64, P < 0.01). Patients with single distant lymph node metastasis have the greatest benefit in nephroureterectomy compared to other specific-site metastases (median survival 19 months vs. 8 months). An understanding of distant metastatic patterns and surgical outcomes in patients with UTUC is important in clinical settings and helpful in the design of personalized treatment protocols.
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Regulatory T (Treg) cells maintain immune homeostasis by inhibiting abnormal/overactive immune responses to both autogenic and nonautogenic antigens. Treg cells play an important role in immune tolerance, autoimmune diseases, infectious diseases, organ transplantation, and tumor diseases. Treg cells have two functional characteristics: T cell anergy and immunosuppression. Treg cells remain immune unresponsive to high concentrations of interleukin-2 and anti-CD3 monoclonal antibodies. In addition, the activation of Treg cells after TCR-mediated signal stimulation inhibits the activation and proliferation of effector T cells. In the process of tumor development, Treg cells accumulate locally in the tumor and lead to tumor escape by inducing anergy and immunosuppression. It is believed that targeted elimination of Treg cells can activate tumor-specific effector T cells and improve the efficiency of cancer immunotherapy. Therefore, inhibition/clearance of Treg cells is a promising strategy for enhancing antitumor immunity. Here, we review studies of cancer immunotherapies targeting Treg cells.
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Imunoterapia , Neoplasias/terapia , Linfócitos T Reguladores/imunologia , Animais , Humanos , Neoplasias/imunologia , Receptores de Citocinas/imunologiaRESUMO
Hypoperfusion is the main cause of anastomotic leakage (AL) following colorectal surgery. The conventional method for evaluating anastomotic perfusion is to observe color change and active bleeding of the resection margin of the intestine and the pulsation of mesenteric vessels. However, the accuracy of this method is low, which may be due to insufficient observation time. A novel surgical procedure that separates the mesentery in advance at the intended transection site can delay the observation of anastomotic perfusion, and can potentially detect more anastomotic sites with insufficient vascular supply and reduce the rate of AL. This study aimed to investigate the effects of a novel surgical procedure on AL following sigmoid colon and rectal cancer surgeries. A total of 343 patients who underwent rectal and sigmoid colon cancer surgeries were included in the study. From August 2021 to June 2022, patients with sigmoid colon or rectal cancer underwent a new surgical procedure of pre-division of the mesentery (PDM) at the intended transection site (PDM group). Patients with colorectal cancer who underwent conventional surgical procedures from August 2018 to July 2021 were categorized as the non-PDM group. Symptomatic AL (SAL) within 30 days and other outcomes were retrospectively analyzed using propensity score matching and compared between the two groups. The incidences of SAL were 1.3% and 11.3% in the PDM and non-PDM groups, respectively. PDM significantly reduced the SAL rate in sigmoid colon and rectal cancer surgeries (P = 0.009). The incidence of total postoperative complications (P < 0.05) was significantly lower in the PDM group than that in the non-PDM group. There were no significant differences between the two groups for operative time (P = 0.662), intraoperative blood loss (P = 0.651), intraoperative blood transfusion (P = 0.316), and intensive care rate (P = 1). The length of postoperative hospital stay (P = 0.010) and first exhaust (P = 0.001) and defecation time (P < 0.05) were shorter in the PDM group than in the non-PDM group. PDM can effectively prevent AL, and this procedure can be safely performed in sigmoid colon and rectal cancer surgeries.
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PURPOSE: The selection of open prostatectomy (OP) over transurethral laser surgery is controversial for large volume prostates. Thus, we aim to compare the efficacy and safety of transurethral laser versus OP, and provide the latest evidence of clinical practice for large-sized benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: This meta-analysis used Review Manager V5.3 software and the systematic literature search of Cochrane Library, Embase, PubMed, and Web of Science datasets was performed for citations published from 2000 to 2020 that compared transurethral laser with OP for the treatment of large BPH. Variables of interest assessing the two techniques included clinical characteristics, and the perioperation-, effectiveness-, and complication-related outcomes. RESULTS: The meta-analysis included twelve studies containing 1,514 patients, with 792 laser and 722 OP. The transurethral laser group was associated with shorter hospital stay and catheterization duration, and less hemoglobin decreased in the perioperative variables. There was no significant difference in the international prostate symptom score, post-void residual urine volume, maximum flow rate, and quality of life score. Transurethral laser group had a significantly lower incidence of blood transfusion than OP group (odds ratio, 0.10; 95% confidence interval, 0.05 to 0.19; p<0.001; I²=8%), and no statistical differences were found with respect to the other complications. CONCLUSIONS: Both OP and transurethral laser prostatectomy are effective and safe treatments for large prostate adenomas. With these advantages of less blood loss and transfusion, and shorter catheterization time and hospital stay, laser may be a better choice for large BPH.
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Hiperplasia Prostática , Ressecção Transuretral da Próstata , Humanos , Lasers , Masculino , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Resultado do TratamentoRESUMO
Metabolic reprogramming of cancer cells is a hallmark of cancer, in which the polar metabolites involving aerobic glycolysis, pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and glutaminolysis play a crucial role in the occurrence and development of cancer. Therefore, targeted analysis of the polar metabolites in these pathways is of great value for understanding cancers, finding diagnostic biomarkers, and identifying therapeutic targets. However, it is still challenging to directly determine polar metabolites in these pathways without derivatization due to their diverse chemical properties, isomers, and strong polarity. Herein, a highly selective and sensitive HILIC-MS/MS method was developed for direct determination of the polar metabolites in aerobic glycolysis, PPP, TCA cycle, and glutaminolysis pathways. Without derivatization, 19 polar metabolites and their isomers with carbonyl, carboxyl, or phosphoryl groups in human plasma and cell extracts of prostate cancer (PC) were determined with strong retention and high resolution. This method has been widely verified by measuring linearity, precision, sensitivity, repeatability, matrix effect, and accuracy. The analysis of plasma samples by HILIC-MS/MS revealed distinct PC-specific metabolic signatures compared to a healthy control. In addition, this method could also be used to screen the targets of metabolic inhibitors at the cellular level. We conclude that the developed HILIC-MS/MS method provides a valuable means to study the cancer metabolic reprogramming or energy metabolism in living organisms.
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Neoplasias da Próstata , Espectrometria de Massas em Tandem , Humanos , Masculino , Cromatografia Líquida , Metabolismo Energético , Interações Hidrofóbicas e HidrofílicasRESUMO
Advancing knowledge of the transcriptome has revealed that circular RNAs (circRNAs) are widely expressed and evolutionarily conserved molecules that may serve relevant biological roles. More interesting is the accumulating evidence which demonstrates the implication of circRNAs in diseases, especially cancers. This revelation has helped to form the rationale for many studies exploring their utility as clinical biomarkers. CircRNAs are highly stable due to their unique structures, exhibit some tissue specificity, and are enriched in exosomes, which facilitate their detection in a range of body fluids. These properties make circRNAs ideal candidates for biomarker development in many diseases. This review will outline the discovery, biogenesis, and proposed functions of circRNAs.
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AIMS: The aim of this study to determine the expression of MMP-28 in bladder urothelial carcinoma and to analyze the correlation between MMP-28 and the clinicopathological characteristics of human bladder carcinoma, and its relationship with patient prognosis. METHODS: A total of 491 surgically resected bladder cancer samples and 80 normal tissue adjacent to the tumor were stained by immunohistochemistry. The expression of MMP-28 in these samples was quantitated, and the value of MMP-28 as a marker of bladder cancer and prognosis was assessed. RESULTS: The expression of MMP-28 in urinary bladder carcinoma was higher than in normal bladder mucosa. The high level of MMP-28 was significantly correlated with tumor histology grade, lymphatic metastasis, lymph node infiltration, and distant metastasis (P < 0.05). The upregulation of MMP-28 was also closely related to the risk of cancer progression and the survival of patients. Further analysis documented that high expression of MMP-28 was associated with decreased overall survival in bladder cancer patients. CONCLUSIONS: The abnormal expression of MMP-28 may be related to the initiation and development of urothelial carcinoma. The upregulation of MMP-28 can be used as one of the effective indicators to diagnose bladder cancer and predict tumor progression.
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Metaloproteinases da Matriz Secretadas/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Biomarcadores Tumorais , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Metaloproteinases da Matriz Secretadas/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
OBJECTIVE: To evaluate the feasibility and safety of transperitoneal laparoscopic nephrectomy in live-donors. METHODS: Two cases of live-donor underwent laparoscopic nephrectomy in May and August 2008 respectively and both were followed up. RESULT: In two cases the operation time was 130, 10 min; blood loss was 50 ml; warm ischemic time was 30 s and 2 min; the length of artery was 4.0 cm and 3.5 cm; the length of vein was 3.0 cm. The grafted kidneys started to produce urine at 30 s and 10 s after blood supply. Renal function of donor returned to normal after two days. The donors were discharged at 7th day after the operation. Renal function of recipient was normal after 3 days. CONCLUSION: Transperitoneal laparoscopic nephrectomy in live-donor is a safe and effective procedure, which provides kidney with satisfactory blood vessels and ureter for graft.
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Transplante de Rim , Laparoscopia , Doadores Vivos , Nefrectomia/métodos , Coleta de Tecidos e Órgãos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peritônio/cirurgiaRESUMO
OBJECTIVE: To evaluate the feasibility and short-term clinical effect of transperitoneal laparoscopic modified retroperitoneal lymph node dissection (LmRPLND) in the management of clinical Stage I nonseminomatous germ cell testicular tumors. METHODS: From October 2004 to July 2006, 7 patients aged 26-36 (mean 30) years underwent LmRPLND with modified unilateral template dissection for clinical Stage I nonseminomatous germ cell testicular tumors, which were 3.0 cm x 2.5 cm x 2.0 cm to 6.5 cm x 4.5 cm x 3.0 cm in size, 3 cases on the left and 4 on the right, all diagnosed by ultrasound, computerized tomography (CT) and chest X-ray and confirmed by biopsy following radical orchiectomy. Those with positive lymph nodes received 3 courses of chemotherapy. RESULTS: Success was achieved in all the 7 cases, the operative time ranging from 120 to 210 min (mean 160 min), blood loss from 50 to 200 ml (mean 150 ml), and with no blood transfusion. The drainage tubes were removed 1-2 days after surgery. The mean postoperative hospital stay was 5.5 days. The follow-up lasted 6-32 (mean 14) months, which revealed normal erection and ejaculation in all the patients, but no major postoperative complications. Pathologically, lymph nodes were negative in 6 cases and positive (1/18) in 1. Normal results were obtained in HCG and AFP tests as well as in retroperitoneal ultrasound and chest X-ray examinations. The patient with positive lymph nodes was treated by adjuvant chemotherapy for 3 courses and found free of malignancy during a 6-month follow-up. CONCLUSION: LmRPLND is a safe and minimally invasive treatment option for patients with clinical Stage I nonseminomatous germ cell testicular carcinoma. With fewer complications and faster recovery, it appears to be a desirable substitute for the open procedure.