OBJECTIVETo report the surgical techniques and results of an 8-year follow-up study of 42 patients with a modified orthotopic ileal neobladder restoring normal anatomical relationship.

METHODSTotal cystoprostatectomy was performed extraperitoneally. A 45 - 50 cm segment of the ileal loop was isolated, detubularized, and reconfigured into an "M"-shape to form a pouch. Bilateral ureters were implanted by inserting 1 cm distal segment into the pouch. The bottom of pouch was opened and anastomosed with the urethra.

RESULTSForty-two patients were followed up for 6 to 96 months,90.5% of whom were continent in the daytime, and 85.7% at night. Two patients had a difficulty in urination. The average volume of the pouch was (361 +/- 48) ml at 12 months postoperation. Urodynamic examination showed the average peak voiding pressure was (86.8 +/- 21.4) cm H(2)O. The average maximum flow rate (Qmax) was (18.4 +/- 6.1) ml/s. No remarkable ureter reflux and obstruction were found. No patient was detected to have urethral carcinoma.

CONCLUSIONSExtraperitoneal cystectomy can avoid the tumor contamination of the abdomen and intestinal interference of the operative field. The ureter-inserting implantation technique is a simple anti-reflux anastomosis method with less ureter stenosis rate. Isolating the neobladder and ureters from the peritoneal cavity can reduce the postoperative complications, such as adhesive ileus, internal hernia, and urine leakage into the peritoneal cavity. The neobladder is similar to the original bladder in position, volume, shape and anti-reflux ureter connection.

Adult ; Aged ; Cystectomy ; methods ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Urinary Reservoirs, Continent

Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down-regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment.
Anoikis ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Connective Tissue Growth Factor ; metabolism ; DNA Methylation ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasm Metastasis ; rho GTP-Binding Proteins ; metabolism ; rho-Associated Kinases ; metabolism

Objective:To investigate the potential risk factors for cryptogenic stroke (CS) in patients with patent foramen ovale (PFO).Methods:Patients underwent PFO closure in the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from June 2018 to December 2021 were enrolled retrospectively. Transesophageal echocardiography was used to evaluate the morphological characteristics of foramen ovale and right-to-left shunt (RLS). Multivariate logistic regression analysis was used to determine the independent risk factors for CS in patients with PFO. Results:A total of 203 patients with PFO were enrolled. Their age was 41.9±14.3, and 116 patients (57.1%) were male. There were 102 patients in CS group and 101 patients in non-stroke group. The age, body mass index, systolic blood pressure and diastolic blood pressure, and the constituent ratios of male, hypertension, diabetes, hyperlipidemia and smoking of the CS group were significant higher than those of the non-stroke group (all P<0.05). The PFO channel of the CS group was longer, wider and more combined with resting RLS (all P<0.05). Multivariate logistic regression analysis showed that systolic blood pressure (odds ratio [ OR] 1.065, 95% confidence interval [ CI] 1.022-1.111; P=0.003), PFO length ( OR 1.124, 95% CI 1.004-1.258; P=0.043) and resting RLS ( OR 5.449, 95% CI 2.283-13.004; P<0.001) were the independent risk factors for CS in patients with PFO. Conclusion:Systolic blood pressure, PFO length and the presence of resting RLS are the independent risk factors for CS in patients with PFO.

Cryptogenic stroke (CS) is a type of stroke that can not find the exact cause after using the standard clinical examination procedure of stroke. In recent years, many studies have shown that patent foramen ovale (PFO) is closely associated with CS, and its main pathogenesis is paradoxical embolism. In clinical practice, ultrasound is often used for PFO screening. In the context of PFO, the secondary prevention of CS includes drug therapy and PFO closure, but the choice of treatment is still controversial. Screening and evaluation of possible PFO will help to develop secondary prevention strategies for patients with CS, especially those who can benefit from PFO closure.

BACKGROUND: Accurate evaluation of lymph node metastasis in bladder cancer (BCa) is important for disease staging, treatment selection, and prognosis prediction. In this study, we aimed to evaluate the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for metastatic lymph nodes in BCa and establish criteria of imaging diagnosis. METHODS: We retrospectively assessed the imaging characteristics of 191 BCa patients who underwent radical cystectomy. The data regarding size, shape, density, and diffusion of the lymph nodes on CT and/or MRI were obtained and analyzed using Kruskal-Wallis test and χ test. The optimal cutoff value for the size of metastatic node was determined using the receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 184 out of 3317 resected lymph nodes were diagnosed as metastatic lymph nodes. Among 82 imaging-detectable lymph nodes, 51 were confirmed to be positive for metastasis. The detection rate of metastatic nodes increased along with more advanced tumor stage (P < 0.001). Once the ratio of short- to long-axis diameter ≤ 0.4 or fatty hilum was observed in lymph nodes on imaging, it indicated non-metastases. Besides, lymph nodes with spiculate or obscure margin or necrosis indicated metastases. Furthermore, the short diameter of 6.8 mm was the optimal threshold to diagnose metastatic lymph node, with the area under ROC curve of 0.815. CONCLUSIONS The probability of metastatic nodes significantly increased with more advanced T stages. Once lymph nodes are detected on imaging, the characteristic signs should be paid attention to. The short diameter > 6.8 mm may indicate metastatic lymph nodes in BCa.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnostic imaging ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Staging ; Pelvic Neoplasms ; diagnostic imaging ; pathology ; secondary ; surgery ; Pelvis ; diagnostic imaging ; pathology ; Tomography, X-Ray Computed ; Urinary Bladder Neoplasms ; diagnostic imaging ; pathology ; surgery

Bladder cancer (BC) is the most common malignant tumor of the genitourinary system. The age of individuals diagnosed with BC tends to decrease in recent years. A variety of standard therapeutic options are available for the clinical management of BC, but limitations exist. It is difficult to surgically eliminate small lesions, while radiation and chemotherapy damage normal tissues, leading to severe side effects. Therefore, new approaches are required to improve the efficacy and specificity of BC treatment. Synthetic biology is a field emerging in the last decade that refers to biological elements, devices, and materials that are artificially synthesized according to users' needs. In this review, we discuss how to utilize genetic elements to regulate BC-related gene expression periodically and quantitatively to inhibit the initiation and progression of BC. In addition, the design and construction of gene circuits to distinguish cancer cells from normal cells to kill the former but spare the latter are elaborated. Then, we introduce the development of genetically modified T cells for targeted attacks on BC. Finally, synthetic nanomaterials specializing in detecting and killing BC cells are detailed. This review aims to describe the innovative details of the clinical diagnosis and treatment of BC from the perspective of synthetic biology.
Humans ; Synthetic Biology ; Urinary Bladder Neoplasms/diagnosis*

BACKGROUNDProstate specific membrane antigen (PSMA) can facilitate the growth, migration, and invasion of the LNCaP prostate cancer cell lines, but the underlying molecular mechanisms have not yet been clearly defined. Here, we investigated whether PSMA serves as a novel regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling by employing PSMA knockdown model and PI3K pharmacological inhibitor (LY294002) in LNCaP prostate cancer cells.

METHODSPSMA knockdown had been stably established by transfecting with lentivirus-mediated siRNA in our previous study. Then, LNCaP cells were divided into interference, non-interference, and blank groups. We first testified the efficacy of PSMA knockdown in our LNCaP cell line. Then, we compared the expression of PSMA and total/activated Akt by Western blotting in the above three groups with or without LY294002 treatment. Furthermore, immunocytochemistry was performed to confirm the changes of activated Akt (p-Akt, Ser473) in groups. Besides, cell proliferation, migration, and cell cycle were measured by CCK-8 assay, Transwell analysis, and Flow cytometry respectively.

RESULTSAfter PSMA knockdown, the level of p-Akt (Ser473) but not of total-Akt (Akt1/2) was significantly decreased when compared with the non-interference and blank groups. However, LY294002 administration significantly reduced the expression of p-Akt (Ser473) in all the three groups. The results of immunocytochemistry further confirmed that PSMA knockdown or LY294002 treatment was associated with p-Akt (Ser473) down-regulation. Decrease of cell proliferation, migration, and survival were also observed upon PSMA knockdown and LY294002 treatment.

CONCLUSIONSTaken together, our results reveal that PI3K/Akt signaling pathway inhibition may serve as a novel molecular mechanism in LNCaP prostate cancer cells of PSMA knockdown and suggest that Akt (Ser473) may play a critical role as a downstream signaling target effector of PSMA in this cellular model.

Antigens, Surface ; genetics ; metabolism ; Cell Line, Tumor ; Glutamate Carboxypeptidase II ; genetics ; metabolism ; Humans ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Prostatic Neoplasms ; enzymology ; genetics ; therapy ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA Interference ; Signal Transduction ; genetics ; physiology

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone