Radical Prostatectomy Without Prior Biopsy in Selected Patients Evaluated by 18F-Labeled Prostate-Specific Membrane Antigen-Ligand Positron Emission Tomography/Computed Tomography and Multiparameter Magnetic Resonance Imaging: A Single-Center, Prospective, Single-Arm Trial.

PURPOSE: This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy. MATERIALS AND METHODS: Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected. RESULTS: All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin. CONCLUSIONS: Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18F-PSMA PET/CT.

A Novel Method for the Rat Model of Abdominal Aortic Aneurysm Induced by Retroperitoneal Implantation of an Osmotic Pump System With Lipopolysaccharide.

BACKGROUND: Few methods can cocurrently mimic the pathological characteristics and nature history of human abdominal aortic aneurysms (AAAs), especially for the exist of the self-healing tendency of rodents. This study tested a novel method for the AAA rat model induced by retroperitoneal implantation of an osmotic pump system with lipopolysaccharide (LPS) based on the hypothesis that chronic inflammation of perivascular adipose tissue directly influenced the development and progression of AAAs. METHODS: 20 male Sprague-Dawley rats (10-month-old) fed with the Paigen diet were randomly divided into 4 groups: the blank group ×2, the sham group ×4, the empty capsule group ×4, and the LPS capsule group ×10. The LPS capsule group received implantations of the ALZET® osmotic pump capsule with LPS (3.6 µg/day) parallel to the abdominal aorta through a retroperitoneal approach. Two weeks later, 6 rats were randomly selected from the LPS capsule group to form the anti-inflammatory group and received implantations of another osmotic pump capsule with interleukin (IL)-10 (75 ng/day) through the same approach. The changes in abdominal aortic diameter were observed by ultrasound every 2 weeks, and samples were harvested for histopathologic and immunohistochemical analysis 6 weeks later. RESULTS: Within the 6 weeks after modeling, the LPS capsule group showed sustained and significant aortic dilatation (P < 0.01), while the anti-inflammatory group showed a rapid and obvious shrinkage 2 weeks after the IL-10 osmotic pump capsule implantation (P < 0.01). The LPS capsule group presented excellent pathological mimicking of human AAAs and showed severe medial degeneration with the least elastic content among the 5 groups at the end of the sixth week (P < 0.05). Notably, the anti-inflammatory group showed perfect medial preservation with the most elastic content (P < 0.05) and the highest elastin/collagen ratio (P < 0.01) at the end of the study. Matrix metalloproteinases (MMP) 2 and 9 and toll-like receptor 2 showed strong expression in the LPS capsule group at the end of the sixth week, which was significantly higher than that in the blank group and sham group. Interestingly, the anti-inflammatory group showed a slightly higher MMP9 expression than the LPS capsule group though there was no statistical difference between them. CONCLUSIONS: This novel method for the rat AAA model induced by retroperitoneal implantation of an osmotic pump capsule with LPS can concurrently mimic the histological characteristics and natural history of human AAAs. Further studies were needed to improve the osmotic pump system.

Incidence and Prognostic Associations of Early Postoperative Stroke and Death Among Patients Undergoing Inner Branched Thoracic Endovascular Repair of Aortic Arch Pathologies: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this systematic review was to assess the incidences and associations of early postoperative stroke and death among patients undergoing inner branched thoracic endovascular aortic repair (TEVAR) of arch pathologies. METHODS: Electronic bibliographic sources (PUBMED, EMBASE, and CENTRAL) were searched up to February 2022 using a combination of thesaurus and free-text terms to identify the studies using branched TEVAR to treat aortic arch disease. The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. All observational studies investigating the prognosis of inner branched TEVAR in the treatment of aortic arch pathologies were included. Independent extraction of articles was performed by two authors using predefined data fields, including study quality indications. All pooled analyses were based on a random-effects or fixed model according to the heterogeneity. RESULTS: A total of 23 case series totaling 532 participants were included after screening. After optimized selection (largest sample size, most detailed data, lowest risk of bias) from the overlapping data, 12 studies with 289 participants were included in data synthesis. The pooled incidence of 30-day postoperative stroke was 10.6% (95% CI 7.0%-14.2%; p=.41, I2=3%). Pooled 30-day mortality was 4.9% (95% CI 2.0%-7.8%; p=.38, I2=7%). Combined early stroke/death was 15.7% (95% CI 11.2%-20.3%; p=.30, I2=15%). Subgroup analyses of 11 studies (without data missing) showed that a higher incidence of 30-day postoperative stroke was found in studies with aged participants (age≥71.3 years, p=.010), the higher percentage of COPD (≥30%, p= .011) and non-dissection-related pathologies (≥60.8%, p=.011). The higher 30-day postoperative mortality was found in studies with a high percentage of previous coronary artery disease (≥34.5%, p=.023). CONCLUSIONS: This review demonstrated that there were acceptable rates of 30-day postoperative stroke and death among patients undergoing inner branched TEVAR. It is strongly necessary to perform a rigorous risk assessment of aortic plaque embolism and coronary artery disease when the surgical plan of the inner branched TEVAR is determined. CLINICAL IMPACT: Treatment arch pathologies with inner branched TEVAR provides acceptable early stroke rate and mortality. Aortic pathology mainly influenced the early stroke rate, and early recognizing high-risk patients for aortic plaque embolism is of supreme importance for reducing the early stroke rate. In addition, the history of coronary artery disease was strongly associated with early mortality, and attention should be paid to the coronary artery assessment and perioperative management of these patients.

Association Between Aneurysm Wall Inflammation Detected by Imaging Perivascular Fat and Secondary Intervention Risk for Abdominal Aortic Aneurysm Patients After Endovascular Repair.

OBJECTIVE: To investigate the association between the imaging biomarker (volumetric perivascular characterization index [VPCI]) which indicates the aortic wall inflammation by mapping the spatial changes of perivascular fat attenuation on computed tomography angiography (CTA) and the reintervention risk for abdominal aortic aneurysm (AAA) patients after endovascular aortic repair (EVAR). METHODS: This case-control study included AAA patients undergoing EVAR from a single center (n=260). Cases were AAA patients undergoing reintervention after EVAR and a 1:1 frequency-matched control group of AAA patients post-EVAR with a shrunken or ≥3-year stable sac and free of reintervention signs during the follow-up. The predictive variable (VPCI trajectory) was converted to binary variables according to the changing trend of VPCI with follow-up time. As a quasi-complete separation data pattern, least absolute shrinkage and selection operator (lasso) regression was used to screen and prove the VPCI trajectory as the best predictor, and the performance was evaluated by calculating the accuracy, sensitivity, and specificity. RESULTS: Between 2010 and 2021, 15 AAA patients after EVAR with type I/III endoleak, aneurysm rupture, or impending rupture were included. Compared with the 1:1 frequency-matched controls with a shrunken or ≥3-year stable sac and free of reintervention signs during the follow-up, VPCI trajectories of the case group were all upward trends, whereas the controls showed 86.7% downward trends (p<0.001). The best predictive model of lasso regressions included 4 variables, and VPCI trajectory was the most outstanding, followed by the proximal landing zone, the distal landing zone, and the infrarenal ß angle. The accuracy, sensitivity, and specificity of predicting the risk of reintervention were as follows, respectively: 93.3%, 100%, and 86.7%. CONCLUSIONS: The wall inflammation detected by imaging perivascular adipose tissue based on the CTAs was strongly associated with the reintervention risk for AAA patients after EVAR, which might hold major promise as a new imaging biomarker for the mechanism and treatment study of human AAAs before and after EVAR. CLINICAL IMPACT: The study introduces a novel imaging biomarker which indicates the aortic wall inflammation by mapping spatial changes of perivascular fat attenuation on CTA. This biomarker demonstrates a strong association with the reintervention risk in AAA patients after EVAR. Incorporation of VPCI into clinical practice has the potential to enhance the traditional surveillance methods (CT/CTAs) by providing clinicians with a non-invasive method to assess aortic wall inflammation and predict the risk of reintervention. Additionally, this study might offer a valuable tool for mechanism and treatment research in humans with AAAs both pre- and post-EVAR, ultimately improving patient outcomes and refining therapeutic strategies.

First-in-Human Clinical Trial of the WeFlow-JAAA Endograft System in Patients With Juxtarenal Abdominal Aortic Aneurysms.

OBJECTIVE: To preliminarily evaluate the safety and efficacy of the WeFlow-JAAA endograft, a novel off-the-shelf device designed for the repair of juxtarenal abdominal aortic aneurysms (JRAAAs) and pararenal abdominal aortic aneurysms (PRAAAs). METHODS: This prospective single-arm first-in-human clinical trial included patients with JRAAAs (infrarenal necks ≤10 mm) or PRAAAs with at least a 5 mm sealing zone below the superior mesenteric artery (SMA) who underwent endovascular repair using the WeFlow-JAAA endograft system. With this system, the celiac artery was addressed with a wide scallop, the renal arteries (RAs) were addressed with 2 standard inner branches, and the SMA was addressed with a "mini-inner-cuff" reinforced fenestration. The primary efficacy endpoint was the clinical success at 12 months. The primary safety endpoint was the freedom from major adverse events (MAEs) in the first 30 days after surgery. RESULTS: Fifteen patients (all men; mean age 68.5±6.0 years) were enrolled between October 2019 and August 2021. The median infrarenal neck length was 0 mm (IQR, 0-4 mm). Technical success was achieved in all patients. No MAEs occurred in the first 30 days. The mean fluoroscopy time was 73.1±27.8 minutes, and the mean volume of contrast media was 130.7±29.4 mL. Clinical success was maintained in all patients at 12 months. No aortic-related deaths, aneurysm rupture, type I or type III endoleak, or open surgery conversion occurred during the follow-up period. The secondary intervention was required only in 1 patient who developed an occluded right RA stent 14 months after the procedure. CONCLUSION: The WeFlow-JAAA endograft device appears to be safe and efficacious in selected patients with JRAAAs or PRAAAs with more than 5 mm sealing zone below SMA. Large-scale, multicenter, and prospective studies with long-term follow-ups are ongoing to validate our findings in China. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04745546 (URL: Guo's Visceral Arteries Reconstruction: The First in Man Study of WeFlow-JAAA Stent Graft System-Full-Text View-ClinicalTrials.gov). CLINICAL IMPACT: The first-in-human clinical trial of the WeFlow-JAAA endograft system demonstrates promising safety and efficacy in treating juxtarenal abdominal aortic aneurysms (JRAAAs) and partial pararenal abdominal aortic aneurysms (PRAAAs). This innovative off-the-shelf device offers a potential alternative to traditional endovascular aortic repair. The successful outcomes, including technical success in all patients, freedom from major adverse events, and maintenance of clinical success at 12 months, suggest a potential shift in clinical practice towards using the WeFlow-JAAA endograft system for selected patients. This study paves the way for larger-scale, multicenter, prospective studies to further validate its long-term safety and efficacy, offering clinicians a new option for managing complex abdominal aortic aneurysms.

Diagnostic accuracy of updated risk assessment criteria and development of novel computational prediction models for patients with suspected choledocholithiasis.

BACKGROUND: There are risks of choledocholithiasis in symptomatic gallstones, and some surgeons have proposed the identification of choledocholithiasis before cholecystectomy. Our goal was to evaluate the diagnostic accuracy of the latest guidelines and create computational prediction models for the accurate prediction of choledocholithiasis. METHODS: We retrospectively reviewed symptomatic gallstone patients hospitalized with suspected choledocholithiasis. The diagnostic performance of 2019 and 2010 guidelines of the American Society for Gastrointestinal Endoscopy (ASGE) and 2019 guideline of the European Society of Gastrointestinal Endoscopy (ESGE) in different risks. Lastly, we developed novel prediction models based on the preoperative predictors. RESULTS: A total of 1199 patients were identified and 681 (56.8%) had concurrent choledocholithiasis and were included in the analysis. The specificity of the 2019 ASGE, 2010 ASGE, and 2019 ESGE high-risk criteria was 85.91%, 72.2%, and 88.42%, respectively, and their positive predictive values were 85.5%, 77.4%, and 87.3%, respectively. For Mid-risk patients who followed 2019 ASGE about 61.8% of them did not have CBD stones in our study. On the choice of surgical procedure, laparoscopic cholecystectomy + laparoscopic transcystic common bile duct exploration can be considered the optimal treatment choice for cholecysto-choledocholithiasis instead of Endoscopic Retrograde Cholangio-Pancreatography (ERCP). We build seven machine learning models and an AI diagnosis prediction model (ModelArts). The area under the receiver operating curve of the machine learning models was from 0.77 to 0.81. ModelArts AI model showed predictive accuracy of 0.97, recall of 0.97, precision of 0.971, and F1 score of 0.97, surpassing any other available methods. CONCLUSION: The 2019 ASGE guideline and 2019 ESGE guideline have demonstrated higher specificity and positive predictive value for high-risk criteria compared to the 2010 ASGE guideline. The excellent diagnostic performance of the new artificial intelligence prediction model may make it a better choice than traditional guidelines for managing patients with suspected choledocholithiasis in future.

A systematic review and meta-analysis of real-world studies evaluating the association between beta-blocker use and postoperative adverse events of carotid endarterectomy.

OBJECTIVE: The objective of this study was to estimate the association of beta-blocker use with postoperative adverse events of carotid endarterectomy (CEA) based on real-world data. METHODS: Electronic bibliographic sources (MEDLINE, EMBASE, and CENTRAL) were searched up to April 2021 using a combination of thesaurus and free-text terms to identify the studies about the effect of beta-blockers on outcomes of CEA. The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. All observational studies and randomized controlled trials investigating the effect of preoperative beta-blockers on the outcomes of CEA were included. Independent extraction of articles by two authors using predefined data fields, including study quality indicators. All pooled analyses were based on a random-effects model. RESULTS: A total of seven observational studies (six case-control studies and one cohort study) were included. Of the three case-control studies that examined the association of beta-blockers with composite postoperative adverse events, two studies including three datasets that totaled 24,161 participants were included in the quantitative synthesis, and the overall results showed a statistically significant association between beta-blocker use and composite postoperative adverse events of CEA (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.15-1.59; P = .0003; I2 = 13%). Publication bias was not present in the meta-analysis (Egger test showed nonsignificant results: P = .453). Two of the included studies utilized indirect measures of cerebral ischemia: intraoperative electroencephalograph, intraoperative hemodynamic indicators; and found a significant association between beta-blockers and intraoperative cerebral ischemia. Another two studies were included for meta-analysis on the association between beta-blockers and 30-day strokes or death of CEA (OR, 1.61; 95% CI, 0.98-2.65; P = .06; I2 = 0%). Of all included studies, there was only one cohort study that reported the association of beta-blockers with postoperative myocardial infarction by χ2 analysis (OR, 1.96; 95% CI, 1.86-2.07). CONCLUSIONS: This systematic review suggested that there was an increased risk of postoperative adverse outcomes of CEA among beta-blocker users compared with nonusers in the real world.

Mechanisms of abdominal aortic aneurysm progression: A review.

Abdominal aortic aneurysm (AAA) is a common disease associated with significant cardiovascular morbidity and mortality. Up to now, there is still controversy on the choice of treatment method of AAA. Even so, the mechanisms of AAA progression are poorly defined, making targeting new therapies problematic. Current evidence favors an interaction of the hemodynamic microenvironment with local and systemic immune responses. In this review, we aim to provide an update of mechanisms in AAA progression, involving hemodynamics, perivascular adipose tissue, adventitial fibroblasts, vasa vasorum remodeling, intraluminal thrombus, and distribution of macrophage subtypes.

Kidney ventrally rotation technique in retroperitoneal robot-assisted partial nephrectomy for posterior hilar tumor: technical feasibility and preliminary results.

PURPOSE: The retroperitoneal robotic assisted partial nephrectomy (RAPN) is suitable for tumors locating on the posterior side of the kidney. However, the posterior hilar tumor poses an additional surgical challenge due to the special location and poor tumor exposure. We developed a novel kidney ventrally rotation technique to overcome this difficulty during retroperitoneal RAPN and evaluated its efficacy in a retrospective case-control comparative study. METHODS: From March 2016 to April 2019, a total of 39 patients with posterior renal hilar tumor underwent retroperitoneal RAPN. The kidney ventrally rotation technique, which improved the tumor exposure by opening the peritoneum and rotating the kidney ventrally, was applied in 24 cases, and the conventional RAPN was performed in the other 15 cases (control group). Perioperative data was analyzed to evaluate the efficacy of the kidney ventrally rotation technique. RESULTS: In kidney rotation group, the 24 patients underwent RAPN successfully without converting to open surgery or radical nephrectomy. The warm ischemia time was 17.4 ± 6.6 min, which was significantly shorter than 24.5 ± 8.3 min in control group. The mean operation time (80 ± 24 min) and estimated blood loss (104 ± 65 ml) were not different from the control group. No sever complications occurred, and no positive surgical margin was found in all the malignant cases. After 14 months follow-up, no recurrence or metastasis occurred in all cases. CONCLUSION: Kidney ventrally rotation technique is safe and feasible for improving the exposure of posterior renal hilar tumor during retroperitoneal RAPN. It could be regarded as an efficient option for the management of posterior hilar tumor.

Identification of aberrantly methylated differentially expressed genes in prostate carcinoma using integrated bioinformatics.

BACKGROUND: Methylation plays a key role in the aetiology and pathogenesis of prostate cancer (PCa). This study aimed to identify aberrantly methylated differentially expressed genes (DEGs) and pathways in PCa and explore the underlying mechanisms of tumourigenesis. METHODS: Expression profile (GSE29079) and methylation profile (GSE76938) datasets were obtained from the Gene Expression Omnibus (GEO). We used R 3.4.4 software to assess aberrantly methylated DEGs. The Cancer Genome Atlas (TCGA) RNA sequencing and Illumina HumanMethylation450 DNA methylation data were utilized to validate screened genes. Functional enrichment analysis of the screened genes was performed, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Gens (STRING). The results were visualized in Cytoscape. After confirmation using TCGA, cBioPortal was used to examine alterations in genes of interest. Then, protein localization in PCa cells was observed using immunohistochemistry. RESULTS: Overall, 536 hypomethylated upregulated genes were identified that were enriched in biological processes such as negative regulation of transcription, osteoblast differentiation, intracellular signal transduction, and the Wnt signalling pathway. Pathway enrichment showed significant changes in factors involved in AMPK signalling, cancer, and adherens junction pathways. The hub oncogenes were AKT1, PRDM10, and FASN. Additionally, 322 hypermethylated downregulated genes were identified that demonstrated enrichment in biological processes including positive regulation of the MAPK cascade, muscle contraction, ageing, and signal transduction. Pathway analysis indicated enrichment in arrhythmogenic right ventricular cardiomyopathy (ARVC), focal adhesion, dilated cardiomyopathy, and PI3K-AKT signalling. The hub tumour suppressor gene was FLNA. Immunohistochemistry showed that AKT1, FASN, and FLNA were mainly expressed in PCa cell cytoplasm, while PRDM10 was mainly expressed in nuclei. CONCLUSIONS: Our results identify numerous novel genetic and epigenetic regulatory networks and offer molecular evidence crucial to understanding the pathogenesis of PCa. Aberrantly methylated hub genes, including AKT1, PRDM10, FASN, and FLNA, can be used as biomarkers for accurate PCa diagnosis and treatment. In conclusion, our study suggests that AKT1, PRDM10, and FASN may be tumour promoters and that FLNA may be a tumour suppressor in PCa. We hope these findings will draw more attention to these hub genes in future cancer studies.

Significant Diagnostic Value of Free-Serum PSA (FPSA)/Prostate-Specific Antigen Density (PSAD) and (F/T)/PSAD for Prostate Cancer of the Chinese Population in a Single Institution.

BACKGROUND The aim of this study was to investigate the diagnostic value of (F/T)/PSAD for prostate cancer detection in the Chinese population. MATERIAL AND METHODS Data were collected retrospectively from patients with prostate cancer or benign prostatic hyperplasia from July 2009 to September 2014. SPSS 19.0 software was used for the receiver operating characteristic curve (ROC), and calculating sensitivity, specificity, and positive predictive values (PPV) and negative predictive values (NPV), respectively. Comparison of the area under ROC (AUC) was performed using the MedCalc v. 10.4.7.0 software. RESULTS A total of 660 patients (including 251 patients with prostate cancer and 409 patients with prostatic hyperplasia) were included. Prostate volume (PV), prostate-specific antigen density (PSAD), free-serum PSA (FPSA)/PSAD, and free-to-total PSA (F/T)/PSAD had similar AUC (P>0.05), and had significantly higher AUC (P<0.001) than F/T, total-serum PSA (TPSA), and free-serum PSA (FPSA). Based on the optimal cutoff value, the sensitivity of (F/T)/PSAD and FPSA/PSAD was similar (P>0.05), and significantly higher than the PV and PSAD (P<0.05). The logistic regression model using a combination of age, FPSA, PV, PSAD, FPSA/PSAD, and (F/T)/PSAD showed higher AUC than each one alone (P<0.001). CONCLUSIONS (F/T)/PSAD can be used as a predictor for prostate cancer in the Chinese population aged >50 years and has a significantly lower false negative rate than PSAD and PV with a cutoff value of ≤0.731. A new parameter, FPSA/PSAD, has similar diagnostic accuracy comparable to (F/T)/PSAD. The diagnostic value of a combination of age, FPSA, PV, PSAD, FPSA/PSAD, and (F/T)/PSAD needs further investigation.

Robot-assisted laparoscopic antegrade versus open inguinal lymphadenectomy: a retrospective controlled study.

BACKGROUND: To investigate the surgical methods and clinical results of robot-assisted laparoscopic antegrade inguinal lymphadenectomy. METHODS: A retrospective study was performed on clinical data from 19 patients with penile cancer admitted from March 2013 to October 2017. Among them, nine patients underwent robot-assisted laparoscopic antegrade inguinal lymphadenectomy (robot-assisted group) and 10 patients underwent open inguinal lymphadenectomy (open group). In the robot-assisted group, preoperative preparation, patient position, robot placement, design of operating channel and establishment of operating space are described. Key surgical procedures and techniques are also summarized. In addition, the number of lymph nodes removed, postoperative complications and follow-up in both groups were statistically analyzed. RESULTS: For the 9 patients in the robot-assisted group, surgery was successfully accomplished at 17 sides without intraoperative conversion to open surgery. The surgery time for each side was 45~90 min using laparoscope with an average of 68.5 ± 13.69 min/side. The intraoperative blood loss was estimated to be < 10 ml/side, and the number of removed lymph nodes was not significantly different from that of the open group (12 ± 4.2/side vs.11 ± 5.8/side, P = 0.84). There were no postoperative complications such as skin necrosis, delayed wound healing and cellulitis in the robot-assisted group. Skin-related complications occurred in 9 (45%) of the 20 sides in the open group. During a median follow-up of 25 months in robot-assisted group and 52.5 mouths in open group, was not significantly different there were no statistical differences in recurrence-free survival between the groups (75% vs 60%, p = 0.536). CONCLUSION: Robot-assisted laparoscopic antegrade inguinal lymphadenectomy achieved the desired surgical outcomes with fewer intraoperative and postoperative complications. The robotic arms of the surgical system were placed between the lower limbs of each patient. There was no need to re-position the robotic arms during bilateral inguinal lymphadenectomy. This simplified the procedure and reduced the use of trocars. If necessary, pelvic lymphadenectomy could be performed simultaneously using the original trocar position.

Whole-genome sequencing revealed armadillo repeat containing 5 (ARMC5) mutation in a Chinese family with ACTH-independent macronodular adrenal hyperplasia.

Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing's syndrome (CS) and is associated with bilateralenlargement of the adrenal glands. It accounts for <1% of all endogenous cases of CS. In order toidentify the pathogenic mutations in the causative gene of (AIMAH pedigrees, Whole-genome sequencing of three patients in family I was used to retrieve candidate causative genes. Meanwhile, the causative gene was identified by Sanger sequencing from the two pedigrees. Sequencing of ARMC5 exons of three patients was carried out to identify somatic mutations. Moreover, haploid clone of one tumor DNA sample was conducted. ARMC5 was the causative gene of two pedigrees confirmed by whole-genome sequencing (WGA) and Sanger sequencing. The variant sites of the two families were c.C943T (p.R315W) and c.C1960T (p.R654X), respectively. Autosomal dominant inheritance of AIMAH was confirmed by genotypes of one family member. Several somatic mutations were discovered in tumor DNA samples. In addition, haploid clone of tumor DNA was confirmed by germline mutation and somaticmutation, which suggested the pathogenic mechanism of "two-hit-model." ARMC5 was the causative gene of AIMAH pedigrees. This AIMAH in this study presented autosomal dominant inheritance, fitting to Mendelian inheritance law. However, the pathogenic mode of this disease showed as compound heterozygote.

MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration.

BACKGROUND: Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. METHODS: MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1. RESULTS: MEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells. CONCLUSIONS: By investigating the role of MEIS1 in ccRCC cells' survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (ccRCC) development.

[Downregulation of PTTG1 expression inhibits the proliferation and invasiveness and promotes the apoptosis of human prostate cancer LNCaP-AI cells].

OBJECTIVE: To investigate the effects of down-regulation of PTTG1 expression on the proliferation, invasiveness and apoptosis of androgen-independent human prostate cancer LNCaP-AI cells and their sensitivity to androgen antagonists. METHODS: Human prostate cancer LNCaP-AI cells were transfected with siRNA targeting the PTTG1 gene using the Lipofectamine 2000 transfection reagent. The proliferation, invasiveness and apoptosis of the cells were detected by MTT, Transwell assay and flow cytometry, respectively. The protein expressions of PTTG1, p-Akt, and p-ERK were determined by Western blot and the mRNA expression of PTTG1 measured by agarose gel electrophoresis. RESULTS: The siRNA expression vector markedly down-regulated the expression of PTTG1, which effectively suppressed the proliferation of the LNCaP-AI cells, with the inhibition rates of (19.47 ± 2.12), (24.01 ± 2.13) and (48.02 ± 2.22)% at 24, 48 and 72 hours, respectively, after transfection, with statistically significant differences among the three groups (P <0.05). The number of the cells passing through the polycarbonate film was remarkably decreased at 24, 48 and 72 hours (74.67 ± 9.85, 56.44 ± 8.66 and 37.33 ± 6.14) as compared with the baseline (111.11 ± 13.47) (P <0.01), while the apoptosis rate of the cells was significantly increased at 24, 48 and 72 hours (18.32 ± 0.94), (19.94 ± 1.30) and (21.73 ± 1.88)% in comparison with the baseline (ï¼»2.17 ± 0.49ï¼½%)， (P <0.05). PTTG1 siRNA combined with androgen antagonist flumatide exhibited even more significant effects in inhibiting the proliferation and promoting the apoptosis of the LNCaP-AI cells than either used alone, and in a flumatide dose-dependent manner. The inhibition and apoptosis rates of the LNCaP-AI cells treated with 50 nmol/L flumatide were (27.13 ± 3.52) and (3.94 ± 0.48)%, and those treated with siRNA + 50 nmol/L flumatide were (67.51 ± 5.13) and (19.93 ± 1.72)%, respectively, both with statistically significant differences between the two groups (P <0.05). The inhibition and apoptosis rates of the cells treated with 100 nmol/L flumatide were (43.72 ± 3.90) and (5.33 ± 0.66)%, and those treated with siRNA + 100 nmol/L flumatide were (73.19 ± 4.78) and (23.43 ± 1.76)%, respectively, both with statistically significant differences between the two groups (P <0.05). CONCLUSIONS: The siRNA expression vector can down-regulate the expression of PTTG1, which can inhibit the proliferation and invasiveness of LNCaP-AI cells, promote their apoptosis, and increase their sensibility to androgen antagonists. Suppressing the expression of PTTG1 may enhance the effect of androgen-deprivation therapy on advanced prostate cancer.

Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS-induced colitis model.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition. Psychological stress has been postulated to affect the clinical symptoms and recurrence of IBD. The exact molecular mechanisms are not fully understood. In the present study, we demonstrate that psychological stress promotes neutrophil infiltration into colon tissues in dextran sulfate sodium (DSS)-induced colitis model. The psychological stress resulted in abnormal expression of the proinflammatory cytokines (IL-1ß, IL-6, IL-17A, and IL-22) and neutrophil chemokines (CXCL1 and CXCL2) and overactivation of the STAT3 inflammatory signaling pathway. Under chronic unpredictable stress, the adrenergic nervous system was markedly activated, as the expression of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in bone marrow and colonic epithelium was enhanced, especially in the myenteric ganglia. The ß-AR agonist isoproterenol mimicked the effects of psychological stress on neutrophilia, neutrophil infiltration, and colonic damage in DSS-induced colitis. The ß1-AR/ß2-AR inhibitor propranolol reduced the numbers of the neutrophils in the circulation, suppressed neutrophil infiltration into colonic tissues, and attenuated the colonic tissue damage promoted by chronic stress. Propranolol also abolished stress-induced upregulation of proinflammatory cytokines and neutrophil chemokines. Our data reveal a close linkage between the ß1-AR/ß2-AR activation and neutrophil trafficking and also suggest the critical roles of adrenergic nervous system in exacerbation of inflammation and damage of colonic tissues in experimental colitis. The current study provides a new insight into the mechanisms underlying the association of psychological stress with excessive inflammatory response and pathophysiological consequences in IBD. The findings also suggest a potential application of neuroprotective agents to prevent relapsing immune activation in the treatment of IBD.

Synergistic antitumor efficacy of combined DNA vaccines targeting tumor cells and angiogenesis.

To further enhance the antitumor efficacy of DNA vaccine, we proposed a synergistic strategy that targeted tumor cells and angiogenesis simultaneously. In this study, a Semliki Forest Virus (SFV) replicon DNA vaccine expressing 1-4 domains of murine VEGFR2 and IL12 was constructed, and was named pSVK-VEGFR2-GFc-IL12 (CAVE). The expression of VEGFR2 antigen and IL12 adjuvant molecule in 293T cells in vitro were verified by western blot and enzyme-linked immune sorbent assay (ELISA). Then CAVE was co-immunized with CAVA, a SFV replicon DNA vaccine targeting survivin and ß-hCG antigens constructed previously. The antitumor efficacy of our combined replicon vaccines was evaluated in mice model and the possible mechanism was further investigated. The combined vaccines could elicit efficient humoral and cellular immune responses against survivin, ß-hCG and VEGFR2 simultaneously. Compared with CAVE or CAVA vaccine alone, the combined vaccines inhibited the tumor growth and improved the survival rate in B16 melanoma mice model more effectively. Furthermore, the intratumoral microvessel density was lowest in combined vaccines group than CAVE or CAVA alone group. Therefore, this synergistic strategy of DNA vaccines for tumor treatment results in an increased antitumor efficacy, and may be more suitable for translation to future research and clinic.

MEIS1 functions as a potential AR negative regulator.

The androgen receptor (AR) plays critical roles in human prostate carcinoma progression and transformation. However, the activation of AR is regulated by co-regulators. MEIS1 protein, the homeodomain transcription factor, exhibited a decreased level in poor-prognosis prostate tumors. In this study, we investigated a potential interaction between MEIS1 and AR. We found that overexpression of MEIS1 inhibited the AR transcriptional activity and reduced the expression of AR target gene. A potential protein-protein interaction between AR and MEIS1 was identified by the immunoprecipitation and GST pull-down assays. Furthermore, MEIS1 modulated AR cytoplasm/nucleus translocation and the recruitment to androgen response element in prostate specific antigen (PSA) gene promoter sequences. In addition, MEIS1 promoted the recruitment of NCoR and SMRT in the presence of R1881. Finally, MEIS1 inhibited the proliferation and anchor-independent growth of LNCaP cells. Taken together, our data suggests that MEIS1 functions as a novel AR co-repressor.

Single-port laparoscopic retroperitoneal surgery using a modified single-port device in urology.

OBJECTIVES: To investigate the use of a flexible instrument platform in performing single-port laparoscopic retroperitoneal urologic surgeries and to verify the safety and feasibility of these surgeries. METHODS: The homemade instrument platform consisted of two control loops and a powder-free surgical glove to form multichannels. 56 patients underwent this kind of single-port surgery for different urologic diseases, including radical nephrectomy in 31 patients, nephroureterectomy in 7 patients, partial nephrectomy in 8 patients, living donor nephrectomy in 4 patients, adrenalectomy in 3 patients, renal cyst surgery in 2 patients and ureterolithotomy in 1 patient. RESULTS: All surgeries were completed successfully with no switch to conventional laparoscopic or open surgery. The mean hospital stay was 13.13 days (range 6-36). All patients were satisfied without major complications. CONCLUSIONS: Retroperitoneal laparoendoscopic single-site surgery using our cost-effective homemade instrument platform appears to be a feasible and safe surgical strategy to perform retroperitoneal laparoscopic urologic surgery.

Modified anatomical retroperitoneoscopic adrenalectomy for adrenal metastatic tumor: technique and survival analysis.

BACKGROUND: In a previous experience, anatomical retroperitoneoscopic adrenalectomy (ARA) was proven safe, effective, and technically efficient for surgical adrenal diseases. However, laparoscopic adrenalectomy for adrenal metastasis is controversial. We evaluated the safety, effectiveness, and efficiency of modified ARA technique for adrenal metastasis and predicted survival factors. METHODS: From 2000 to 2010, a consecutive series of 75 patients with adrenal metastases underwent 78 ARAs (three bilateral ARAs). Three modifications and one key procedure were specified in this study. Medical records and follow-up data were retrospectively studied. Then, the surgery data of ARA were compared with those of other approaches to evaluate its safety, effectiveness, and efficiency. Additionally, univariate and multivariate analyses were used to predict the risk factors for survival. RESULTS: The most common primary tumor was renal cell carcinoma (RCC, n = 26), followed by non-small-cell lung carcinoma (NSCLC, n = 23), and hepatocellular carcinoma (HCC, n = 12). A total of 76 successful ARAs and two conversions to open surgery were performed, with a median operation time of 53 (range, 40-250) min and median estimated blood loss of 25 (range, 10-700) mL. The local recurrence rate was 5.3 %, and the median survival was 24 months. These data were comparable with or even better than other approaches in previous studies. The independent prognostic factors of survival were body mass index (BMI, p < 0.001), tumor type (p < 0.001), tumor size (≥ 4 cm vs. <4 cm, p = 0.017), and margin status (negative vs. positive, p = 0.011). CONCLUSIONS: ARA is a safe and effective approach for the management of adrenal metastasis in selected patients. BMI, tumor type, tumor size, and margin status may independently predict survival.