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BACKGROUND: The controversy surrounding Roux-en-Y (R-Y) and Billroth II with Braun (BII + B) reconstruction as an anti-bile reflux procedure after distal gastrectomy has persisted. Recent studies have demonstrated their efficacy, but the long-term outcomes and postoperative quality of life (QoL) among patients have yet to be evaluated. Therefore, we compared the short-term and long-term outcomes of the two procedures as well as QoL. METHODS: The clinical data of 151 patients who underwent total laparoscopic distal gastrectomy (TLDG) at the Gastrointestinal Surgery Department of the Second Hospital of Fujian Medical University from January 2016 to December 2019 were retrospectively analyzed. Of these, 57 cases with Roux-en-Y procedure (R-Y group) and 94 cases with Billroth II with Braun procedure were included (BII + B group). Operative and postoperative conditions, early and late complications, endoscopic outcomes at year 1 and year 3 after surgery, nutritional indicators, and quality of life scores at year 3 postoperatively were compared between the two groups. RESULTS: The R-Y group recorded a significantly longer operative time (194.65 ± 21.52 vs. 183.88 ± 18.02 min) and anastomotic time (36.96 ± 2.43 vs. 27.97 ± 3.74 min) compared to the BII + B group (p < 0.05). However, no other significant differences were observed in terms of perioperative variables, including blood loss (p > 0.05). Both groups showed comparable rates of early and late complications. Endoscopic findings indicated similar food residuals at years 1 and 3 post-surgery for both groups. The R-Y group had a lower occurrence of residual gastritis and bile reflux at year 1 and year 3 after surgery, with a statistically significant difference (p < 0.001). Reflux esophagitis was not significantly different between the R-Y and BII + B groups in year 1 after surgery (p = 0.820), but the R-Y group had a lower incidence than the BII + B group in year 3 after surgery (p = 0.023). Nutritional outcomes at 3 years after surgery did not differ significantly between the two groups (p > 0.05). Quality of life scores measured by the QLQ-C30 scale were not significantly different between the two groups. However, on the QLQ-STO22 scale, the reflux score was significantly lower in the R-Y group than in the BII + B group (0 [0, 0] vs. 5.56 [0, 11.11]) (p = 0.003). The rest of the scores were not significantly different (p > 0.05). CONCLUSION: Both R-Y and B II + B reconstructions are equally safe and efficient for TLDG. Nevertheless, the R-Y reconstruction reduces the incidence of residual gastritis, bile reflux, and reflux esophagitis, as well as postoperative reflux symptoms, and provides a better quality of life for patients. R-Y reconstruction is superior to BII + B reconstruction for TLDG.
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Refluxo Biliar , Esofagite Péptica , Gastrite , Laparoscopia , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Qualidade de Vida , Refluxo Biliar/epidemiologia , Refluxo Biliar/etiologia , Refluxo Biliar/cirurgia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Gastroenterostomia/efeitos adversos , Gastroenterostomia/métodos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Anastomose em-Y de Roux/efeitos adversos , Anastomose em-Y de Roux/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Esofagite Péptica/epidemiologia , Esofagite Péptica/etiologia , Esofagite Péptica/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologiaRESUMO
BACKGROUND: To compare short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis for laparoscopic total gastrectomy. METHODS: This retrospective cohort study included patients with gastric cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to March 2020. Quality of life, intraoperative and postoperative conditions were analyzed. RESULTS: Compared with the conventional assisted group, the modified overlap group showed a shorter auxiliary incision, milder postoperative pain, shorter time to the first postoperative anal exhaust, shorter time to the first postoperative liquid food intake, and shorter postoperative stay. There were no differences between the two groups regarding operation time, esophagus-jejunum anastomosis time, intraoperative blood loss, number of lymph nodes dissected, and length of the upper incision margin. There were no differences between the two groups regarding postoperative early and late complications. There were no differences between the two groups regarding the QLQ-C30 scale three years after the operation. The scores of the QLQ-STO22 scale 3 years after the operation showed significantly lower scores for dysphagia and feeding limit in the modified overlap group than those in the conventional assisted anastomosis group. There was no recurrence in the modified overlap group but one patient in the conventional assisted group. CONCLUSIONS: Patients undergoing totally laparoscopic total gastrectomy with modified overlap anastomosis have better minimal invasiveness and faster post-operative recovery than conventional incision-assisted anastomosis.
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Laparoscopia , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Qualidade de Vida , Laparoscopia/efeitos adversos , Anastomose Cirúrgica/efeitos adversos , Gastrectomia/efeitos adversos , Neoplasias Gástricas/patologia , Resultado do Tratamento , Complicações Pós-Operatórias/etiologiaRESUMO
In this experiment, Genetically improved farmed Nile tilapia Oreochromis niloticus were intraperitoneally injected with 1â¯g glucose/kg of body weight or saline. Red and white muscle tissues were collected at 0, 1, 2, 4, 6 and 12â¯h after the glucose tolerance test (GTT) or saline injection, and the time course of changes in molecular and metabolic adaption of glucose metabolism of these two tissues were evaluated. The results showed that the expression of insulin-responsive glucose transporter 4 (glut4) was up-regulated at 4â¯h after the GTT in the red muscle, implying an increase of glucose uptake. However, the expression of glut4 in the white muscle did not change with glucose load. The glycolysis of red muscle in tilapia was stimulated during 2-4â¯h after the GTT, as the expression of hexokinase 1b (hk1b), hk2, phosphofructokinase muscle type a (pfkma) and pfkmb and the activity of HK and PFK increased. By contrast, only the expression of hk1b was up-regulated at 6â¯h after the GTT in the white muscle. The mRNA level of glycogen synthase 1 (gys1) and glycogen content increased at 2 and 6â¯h, respectively after the GTT in the red muscle, suggesting that glucose storage was provoked. However, glycogen content in the white muscle was not impacted by GTT. Lipogenesis was stimulated in the red muscle as reflected by up-regulated expression of acetyl-CoA carboxylase α (accα) (during 2-4â¯h) and accß (during 4-12â¯h) with GTT. In the white muscle, however, the expression of accα was not changed, and mRNA level of accß was not up-regulated until 6â¯h after the GTT. Taken together, it was concluded that the glycolytic and glycogen synthesis mechanisms in the red muscle were highly regulated by an acute glucose load while those in the white muscle were less responsive to this stimulus.
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Adaptação Fisiológica , Ciclídeos/metabolismo , Glucose/metabolismo , Músculos/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Animais Geneticamente Modificados , Ciclídeos/genética , Teste de Tolerância a Glucose , Glicogênio/metabolismo , Glicogênio Sintase/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Masculino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Fosfofrutoquinases/metabolismoRESUMO
BACKGROUND: Bladder cancer is the most common malignancy in urinary system and the ninth most common malignancy in the world. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation and play essential roles during cancer development. We investigated the expression of miR-135a in bladder cancer and explored its bio-function during bladder cancer progression. METHODS: The expression of miR-135a in bladder cancer cells and tissues are performed by using Real-time PCR assay. Cell viability assay (MTT assay), colony formation assay, anchorage-independent growth ability assay and Bromodeoxyuridine labeling and immunofluorescence (BrdUrd) assay are used to examine cell proliferative capacity and tumorigenicity. Flow cytometry analysis is used to determine cell cycle progression. The expressions of p21, p27, CyclinD1, Ki67, PHLPP2 and FOXO1 are measured by Western blotting assay. Luciferase assay is used to confirm whether FOXO1 is the direct target of miR-135a. RESULTS: miR-135a is upregulated in bladder cancer cells and tissues. Enforced expression of miR-135a promotes bladder cancer cells proliferation, whereas inhibition of miR-135a reverses the function. Furthermore, for the first time we demonstrated PHLPP2 and FOXO1 are direct targets of miR-135a and transcriptionally down-regulated by miR-135a. Suppression of PHLPP2 or FOXO1 by miR-135a, consisted with dysregulation of p21, p27, Cyclin D1 and Ki67, play important roles in bladder cancer progression. CONCLUSION: Our study demonstrates that miR-135a promotes cell proliferation in bladder cancer by targeting PHLPP2 and FOXO1, and is performed as an onco-miR.
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Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Fosfoproteínas Fosfatases/genética , Transcrição Gênica , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Sequência de Bases , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Humanos , Antígeno Ki-67/metabolismo , MicroRNAs/genética , Modelos Biológicos , Dados de Sequência Molecular , Fosfoproteínas Fosfatases/metabolismoRESUMO
PURPOSE: In the present study, we aimed to evaluate the efficacy and safety of camrelizumab combined with oxaliplatin plus S-1 in patients with resectable gastric or gastroesophageal junction cancer. METHODS: In this single-arm, phase II clinical trial, patients with locally advanced gastric or gastroesophageal junction adenocarcinoma were enrolled to receive three cycles of neoadjuvant camrelizumab and oxaliplatin plus S-1 every 3 weeks, followed by surgical resection and adjuvant therapy with the same regimen. The primary endpoint was pathological complete response (pCR) (ypT0) rate and secondary endpoints were R0 resection rate, total pCR (tpCR, ypT0N0) rate, major pathological response (MPR) rate, downstaging, objective response rate (ORR), disease control rate (DCR), event-free survival (EFS), overall survival (OS), and safety. RESULTS: Between September, 2020 and January, 2022, a total of 29 patients were enrolled in the present study, all of whom completed neoadjuvant therapy and underwent surgery. Three (10.3%) (95% CI: 2.2-27.4) patients achieved pCR as well as tpCR, 20 (69.0%) patients had MPR and 28 (96.6%) patients achieved R0 resection. Treatment-emergent adverse events (AEs) of any grade were observed in 24 (82.8%) patients. Immune-related adverse events of any grade were reported in 13 (44.8%) patients, whereas no grade 3 or higher adverse events occurred. CONCLUSION: The neoadjuvant therapy with camrelizumab in combination with oxaliplatin and S-1 showed a modest pCR rate, and favorable MPR rate and safety profile in patients with gastric or gastroesophageal junction cancer.
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Anticorpos Monoclonais Humanizados , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Oxaliplatina , Junção Esofagogástrica , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: Invasive urothelial carcinoma (UC) with squamous and glandular differentiation is a highly malignant and complicated pathological subtype, and the standard care is radical cystectomy (RC). However, urinary diversion after RC significantly reduces patient quality of life, thus bladder-sparing therapy has become a research hotspot in this field. Recently, five immune checkpoint inhibitors have been approved for systemic therapy of locally advanced or metastatic bladder cancer by the Food and Drug Administration, but the efficacy of immunotherapy combined with chemotherapy for invasive UC is still unknown, especially for pathological subtypes with squamous and glandular differentiation. CASE SUMMARY: We report the case of a 60-year-old male who complained of repetitive painless gross hematuria and was diagnosed with muscle-invasive bladder cancer with squamous and glandular differentiation, defined as cT3N1M0 according to the American Joint Committee on Cancer, who had a strong desire to preserve the bladder. Immunohistochemical staining revealed that programmed cell death-ligand 1 (PD-L1) expression in the tumor was positive. Thus, a transurethral resection to maximize removal of the bladder tumor was performed under cystoscopy, and the patient subsequently received a combination of chemotherapy (cisplatin/gemcitabine) and immunotherapy (tislelizumab) treatment. No tumor recurrence in the bladder was observed following pathological and imaging examination after 2 cycles and 4 cycles of treatment, respectively. The patient achieved bladder preservation and has been tumor-free for more than two years. CONCLUSION: This case shows that the combination of chemotherapy and immunotherapy might be an effective and safe treatment strategy for PD-L1 expression positive UC with divergent histologic differentiation.
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OBJECTIVES: To analyze the perioperative complications of radical cystectomy using a standardized reporting methodology. METHODS: The clinical data of 233 cases of radical cystectomy from January 1996 to December 2008 were reviewed. Two hundred male patients and 33 female patients were included. The mean age was 58.9 years old. All complications within 30 days of surgery were recorded and classified using a 5-grade modification of the Clavien system. RESULTS: Overall mean operative time was 339 (170 - 610) minutes, and mean blood loss was 818 (range 100 to 3500) ml. Of the 233 subjects at least 1 postoperative complication developed in 84 (36.1%), including five cases of intraoperative complications. According to the modified Clavien system, 27 patients (11.6%) had grade 1, 38(16.3%) had grade 2, 16(6.9%) had grade 3, and 3(1.7%) had grade 4 complications. The most frequent complication was gastrointestinal complications (15.9%), then the incision-related complications (15.0%) and lung infections (4.7%). An association between hypoproteinemia and any complication was found after adjusting for confounding variables (OR = 2.963, 95%CI: 1.451 - 6.050, P = 0.003), and American society of anesthesia score (ASA score) was significantly associated with any major complication (OR = 2.520, 95%CI: 1.003 - 6.332, P = 0.049). CONCLUSIONS: Radical cystectomy is associated with a high perioperative complications, using the modification of the Clavien system has allowed us to stratify complications during radical cystectomy. Hypoproteinemia is independently associated with any complication in these patients and ASA score was significantly associated with any major complication.
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Cistectomia , Complicações Pós-Operatórias/classificação , Neoplasias da Bexiga Urinária/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Giant renal angiomyolipomas (AMLs) may lead to complications including flank pain, hematuria, hypertension, retroperitoneal hemorrhage and even death. Giant AMLs which grow around renal hilar vessels and the ureter are rare. Most previous reports on the treatment of giant renal AMLs have focused on open surgery or a transperitoneal approach, with few studies on the retroperitoneal approach for large AMLs. We here report a case of giant renal hilum AML successfully treated with robot-assisted laparoscopic nephron sparing surgery the retroperitoneal approach, with a one-year follow-up. CASE SUMMARY: A 34-year-old female patient was diagnosed with renal AML 11 years ago and showed no discomfort. The tumor gradually increased in size to a giant AML over the years, which measured 63 mm × 47 mm ×90 mm and was wrapped around the right hilum. Therefore, a robotic laparoscopic partial nephrectomy (LPN) via the retroperitoneal approach was performed. The patient had no serious postoperative complications and was discharged soon after the operation. At the one-year follow-up, the patient's right kidney had recovered well. CONCLUSION: Despite insufficient operating space via the retroperitoneal approach, LPN for giant central renal AMLs can be completed using a well-designed procedure with the assistance of a robotic system.
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In order to obtain a full-length expression plasmid for human PDLIM2 gene, fragment amplification was used to clone its full-length coding sequence (CDS) region. The amplified PCR product was then digested and inserted into the pMD 18-T vector and subcloned into the pIRES2-EGFP plasmid to form the pIRES2-EGFP-PDLIM2 eukaryotic expression vector. After it was transfected to the bladder cancer cell line, BIU-87, the biological activities of high expression were verified by RT-PCR and Western blotting. Meanwhile the mRNA and protein expressions of p65 were detected. Finally we analyzed the effect of overexpressed PDLIM2 on BIU-87 cell proliferation. In conclusion, a recombinant eukaryotic expression vector pIRES2-EGFP-PDLIM2 containing the complete CDS region of PDLIM2 was successfully constructed. PDLIM2 negatively regulated p65 expression and inhibited BIU-87 cell proliferation. We laid the foundations for further research into the function of the PDLIM2 gene in bladder cancer.
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Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Plasmídeos , Linhagem Celular Tumoral , Proliferação de Células , Clonagem Molecular , Vetores Genéticos , Humanos , Reação em Cadeia da Polimerase , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To assess the role of transrectal ultrasonography (TRUS) in the etiological diagnosis of male obstructive azoospermia. METHODS: We retrospectively analyzed the clinical data and TRUS findings of 695 patients with obstructive azoospermia from January 2007 to May 2009. RESULTS: Concerning the etiology of obstructive azoospermia, the main TRUS findings included ejaculatory duct abnormality (29.2%), seminal vesicle abnormality (25.4%) and prostate midline cyst (18.5%). TRUS revealed 203 cases of ejaculatory duct dilation, 177 cases of seminal vesicle abnormality (including 108 with absence or agenesis and 51 with dilation of the seminal vesicle), and 128 cases of prostate midline cyst (including 75 with ejaculatory duct cyst and 39 with Müllerian cyst). Calcification of the verumontanum or ejaculatory duct was suspected to be the causes of obstructive azoospermia in 34 cases. However, no significant etiological abnormality was found in 153 cases. Obvious etiology was shown by TRUS in 78.0% of the patients. CONCLUSION: TRUS can clearly display the structural abnormality of the ejaculatory duct and seminal vesicle, and provide important information on the etiology of male obstructive azoospermia.
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Azoospermia/diagnóstico por imagem , Azoospermia/etiologia , Reto/diagnóstico por imagem , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , UltrassonografiaRESUMO
OBJECTIVE: To discuss the risk factors of recurrent non-muscle-invasive bladder cancer and elucidate its clinical significance. METHODS: The retrospective survival analysis of 161 patients with non-muscle-invasive bladder cancer was performed by Kaplan-Meier method, Log-rank test and COX proportional hazard model. RESULTS: On univariate analysis, the parameters of tumor stage, tumor grade, number of tumors and previous recurrence were significant for tumor recurrence (all P < 0.05). On multivariate analysis of COX proportional hazard model, all the above risk factors remained significant for tumor recurrence. The hazard ratios were as follows: tumor stage (RR = 3.810, P = 0.001), tumor grade (RR = 2.416, P = 0.009), number of tumors (RR = 1.736, P = 0.036) and previous recurrence (RR = 1.810, P = 0.010). CONCLUSION: Tumor stage and tumor grade plays the most important role in tumor recurrence.
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Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: To compare hand-assisted laparoscopic radical cystectomy (HALRC) with the standard laparoscopic radical cystectomy (LRC) in an attempt to delineate their role in bladder cancer treatment. METHODS: We retrospectively analyzed 51 patients who underwent HALRC (HALRC group, 31 cases) or LRC (LRC group, 20 cases). Urinary diversion was performed extracorporeally through the hand port or the incision for specimen retrieval, respectively, in the two groups. Baseline patient characteristics, intraoperative parameters, and postoperative outcomes were evaluated. RESULTS: There was no statistically significant difference in age, sex, body mass index, previous abdominal surgeries, or tumor stage between the two groups. Although the LRC group yielded a significantly smaller incision for urinary diversion than the HALRC group (7.3 cm vs 6.2 cm, P < 0.05), mean operative time, mean estimated blood loss, blood transfusion rate, time to oral intake and complications were similar in the two groups. Hernia formation was observed with increased frequency in the HALRC group. No patients in the HALRC group and only one patient (5%) in the LRC group presented a positive margin. CONCLUSIONS: The HALRC group yielded the same outcomes as the LRC group, except with a larger incision. The hand-assisted approach might be preferred for obese patients or those having multiple previous abdominal surgeries.
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Cistectomia/métodos , Laparoscopia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Protein kinase C epsilon (PKCε), a member of the novel PKC family, is known to be a transforming oncogene and tumor biomarker for many human solid cancers including renal cell carcinoma (RCC). We isolated side population (SP) cells from the RCC 769P cell line, and proved that those cells possess cancer stem cell (CSC) characteristics. In this study, to identify the function of PKCε in cancer stemness of 769P SP cells, we reduced the expression of PKCε in those cells, following the results demonstrated that PKCε depletion had a negative correlation with the existence of SP cells in 769P cell line. Down-regulation of PKCε also suppresses the CSC potential of sorted 769P SP cells in several ways: proliferation potential, resistance to chemotherapeutics and in vivo tumor formation ability. Our study also reveals that PKCε is associated with ABCB1 and this association probably contributed to the SP cells isolation from 769P cell line. Furthermore, the expression of ABCB1 is directly regulated by PKCε. Additionally, after the depletion of PKCε, the phosphorylation of pAkt, pStat3 and pERK was apparently suppressed in 769P SP cells, whereas PKCε overexpression could promote the phosphorylation of AKT, STAT3 and ERK in 769P Non-SP cells. Overall, PKCε down-regulation suppresses sorting and the cancer stem-like phenotype of RCC 769P SP cells through the regulation of ABCB1 transporter and the PI3K/Akt, Stat3 and MAPK/ERK pathways that are dependent on the phosphorylation effects. Thus, PKCε may work as an important mediator in cancer stem cell pathogenesis of renal cell cancer.
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Carcinoma de Células Renais/enzimologia , Separação Celular/métodos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Renais/enzimologia , Células-Tronco Neoplásicas/enzimologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteína Quinase C-épsilon/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células da Side Population/enzimologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células , Relação Dose-Resposta a Droga , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Fenótipo , Fosforilação , Interferência de RNA , Fator de Transcrição STAT3/metabolismo , Células da Side Population/efeitos dos fármacos , Células da Side Population/patologia , Transdução de Sinais , Fatores de Tempo , TransfecçãoRESUMO
Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells as compared with other four cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Células-Tronco Neoplásicas/patologia , Células da Side Population/patologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Carcinoma de Células Renais/genética , Diferenciação Celular/genética , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Renais/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Transplante HeterólogoRESUMO
BACKGROUND: Multiple recurrences are common in non-muscle invasive bladder cancer, but the risk of multiple recurrences has not been fully described. Identifying patients at high risk of multiple recurrences will help to select an optimal therapeutic strategy and to improve prognosis. This study was conducted to identify the risk factors for multiple recurrences of non-muscle invasive bladder cancer. METHODS: We reviewed the clinical data of all patients with non-muscle invasive bladder cancer in our hospital between January 2003 and February 2010. Patients with at least one recurrence were included. Multivariate analysis was performed for theorized risk factors (age, gender, tumor stage, grade, size, location, number of lesions, adjuvant intra-vesical chemotherapy after transurethral resection, and recurrence-free survival after each resection) to clarify risk factors for multiple recurrences of non-muscle invasive bladder cancer. RESULTS: Of the 278 patients with non-muscle invasive bladder cancer, 84 were with at least one recurrence and a total of 222 recurrences among them were followed up for 6 - 70 months (mean, 36.1 months). Recurrence-free survival after initial resection predicted the overall frequency of bladder cancer recurrence (risk ratio (RR) = 37.83, 95% confidence interval (CI) = 3.45 - 396.13, P = 0.001) and second recurrence (RR = 6.15, 95%CI = 1.28 - 29.57, P = 0.023). Similarly, recurrence-free survival after a second resection was the only significant risk factor for third recurrence (RR = 31.08, 95%CI = 2.53 - 381.47, P = 0.007). Moreover, recurrence-free survival after initial resection was the only significant factor to predict later progression to muscle invasive bladder cancer (RR = 8.62, 95%CI = 1.47 - 58.34, P = 0.001). CONCLUSIONS: Recurrence-free survival after resection is an independent predictor of multiple recurrences of non-muscle invasive bladder cancer. The shorter the period between resection and recurrence is, the higher the risk of multiple recurrences.
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Cistectomia/métodos , Recidiva Local de Neoplasia/etiologia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Uretra , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Mitochondrial tumor suppressor 1 (MTUS1) is a newly identified candidate tumor suppressor gene. Previous studies have demonstrated that the expression status of MTUS1 is altered in several types of tumors. However, its clinical significance for bladder cancer patients remains undetermined. In this study, we detected the expression of MTUS1 mRNA in bladder tumors and paired normal samples obtained from 5 patients using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). A significant downregulation of MTUS1 mRNA expression was observed in the tumor tissues compared with the corresponding normal bladder tissue (P<0.001). We further tested the expression of MTUS1 mRNA in 55 bladder cancer tissues and 10 adjacent normal bladder tissues by quantitative real-time RT-PCR. Correlations between MTUS1 and clinicopathological features and prognosis were investigated by statistical analyses. The results showed that MTUS1 expression was correlated with tumor grade, stage, size and number (P<0.001, P<0.001, P=0.034 and P=0.029, respectively). Patients with low levels of MTUS1 mRNA expression had a poor prognosis compared with those with a high expression (P<0.001). Univariate and multivariate logistic regression prognostic analyses revealed that MTUS1 mRNA was an independent prognostic factor for disease-free survival in bladder cancer (P<0.05). In conclusion, these data suggest that MTUS1 is significant in the progression of bladder cancer and that the status of MTUS1 mRNA expression is a novel prognostic marker for predicting bladder tumor disease-free survival.
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PURPOSE: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). MATERIALS: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. RESULTS: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 LI≤25%, VEGF scoring≤8), mG2 (Ki67 LI>25%, VEGF scoring≤8; or Ki67 LI≤25%, VEGF scoring>8), and mG3 (Ki67 LI>25%, VEGF scoring>8), which can indicate favorable, intermediate and poor prognosis, respectively. CONCLUSIONS: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.
Assuntos
Biomarcadores Tumorais/metabolismo , Antígeno Ki-67/metabolismo , Modelos Estatísticos , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
OBJECTIVES: To evaluate the prognostic impact of hydronephrosis in bladder cancer treated by radical cystectomy. METHODS: We performed a retrospective review of 126 patients with transitional cell carcinoma of bladder, who underwent radical cystectomy at our hospital from January 2003 through May 2010. The relationship between hydronephrosis, tumor stage, and lymph node status was analyzed. We evaluated the effect of hydronephrosis on the recurrence-free survival of bladder cancer by using log-rank test and multivariate Cox regression analysis. RESULTS: Thirty-four patients had unilateral hydronephrosis and five patients had bilateral hydronephrosis. There were 59.0% of tumors with stage ≥pT3a, and 30.8% with pT2, 10.2% with pT1 in the Hydronephrosis group respectively compared to 14.9%, 59.8%, and 25.3% in the Non-hydronephrosis group (χ2 = 25.680, P<0.001). The 5-year recurrence-free survival rates in the Hydronephrosis group were significantly lower than the Non-hydronephrosis group (42.5±10.3% vs. 68.8±8.1%, P=0.001). When adjusted to the different stages stratum, the recurrence-free survival rates among patients with stage pT1-2pN- or lymph node metastasis did not differ significantly whether they had evidence of preoperative hydronephrosis or not, while they differed significantly in the subgroup of stage ≥pT3a,pN-. Multivariate analysis showed that hydronephrosis was not an independent prognostic factor for recurrence-free survival except pathological stage and lymph node status. CONCLUSIONS: Preoperative hydronephrosis predicts advanced stages in transitional cell carcinoma of bladder and exactly effects the survival mainly in higher stage tumor without metastasis.
Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Hidronefrose/etiologia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/complicações , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/secundário , Intervalo Livre de Doença , Feminino , Humanos , Hidronefrose/epidemiologia , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/mortalidade , Derivação UrináriaRESUMO
BACKGROUND & OBJECTIVE: With the development of laparoscopic technique, more and more renal cancer patients have accepted laparoscopic radical nephrectomy instead of open radical nephrectomy. This study was to introduce our experiences of retroperitoneoscopic radical nephrectomy, and evaluate its therapeutic efficacy. METHODS: Between Nov. 2003 and Aug. 2006, retroperitoneoscopic radical nephrectomy was performed in 43 renal cancer patients; retroperitoneal approach was structured without water balloon, and Hem-o-lok clips were used to control renal vessels during operation. In the same period, open radical nephrectomy was performed in 34 renal cancer patients. Treatment outcomes of the 2 groups were compared. RESULTS: There was no significant difference in operation time between laparoscopy group and open approach group (149 min vs. 140 min, P=0.24). The amount of blood loss during operation was significantly less in laparoscopy group than in open approach group (53 ml vs. 199 ml, P<0.01). The time of intestinal function recovery, ambulation, indwelling drainage tube, and hospitalization stay after operation were significantly shorter in laparoscopy group than in open approach group (P<0.01). Incision infection occurred in 2 patients in open approach group; no severe perioperative complications presented in laparoscopy group. During the follow-up of 1-32 months, 1 patient in open approach group had lung metastasis; none in laparoscopy group had recurrence or metastasis. CONCLUSIONS: Retroperitoneoscopic radical nephrectomy has the advantages of mini-invasion and rapid recovery. The method of structuring retroperitoneal approach without water balloon is safe and effective. Hem-o-lok clip is a reliable and economical device for renal vascular control.