Guoxi Zhang

Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma

BackgroundFork head box M1 (FoxM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC). Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models.MethodsReal-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA) in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed.ResultsFoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P <0.001), lymph node metastasis (P = 0.01), distant metastasis (P = 0.01), TNM stage (P < 0.001) and histological grade (P = 0.003). The Kaplan–Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P < 0.001). FoxM1 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis (P = 0.008). Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF), resulting in the inhibition of migration, invasion, and angiogenesis.ConclusionsThese results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a promising therapeutic target for ccRCC.

A one-port pneumovesicum method in en bloc laparoscopic nephroureterectomy with bladder cuff resection is feasible and safe for upper tract transitional cell carcinoma

Study Type – Therapy (case series)

Transvaginal Natural Orifice Transluminal Endoscopic Nephrectomy in a Series of 63 Cases: Stepwise Transition From Hybrid to Pure NOTES

BACKGROUND The feasibility of hybrid transvaginal NOTES (natural orifice transluminal endoscopic surgery) nephrectomy (HTNN) has already been demonstrated. However, pure transvaginal NOTES nephrectomy (PTNN) has been limited to animal experiments with only one report of its use in humans. OBJECTIVE To describe our initial experience with HTNN and a stepwise transition towards PTNN. DESIGN, SETTING, AND PARTICIPANTS Between May 2010 and September 2011, 63 patients underwent nephrectomy (60 HTNNs and 3 PTNNs) in our institution, including 45 patients with benign renal disease and 18 patients with malignant renal disease. SURGICAL PROCEDURE Of the HTNNs, 33 were performed using two umbilical trocars and one transvaginal trocar, and 27 were performed using one umbilical trocar and a transvaginal multi-instrument access port; 3 PTNNs were performed using a self-developed, three-channel ZOU-port without any transumbilical assistance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS All data referring to patient demographics, surgery, pathology, and perioperative outcomes were recorded. Sexual function was assessed with the Female Sexual Function Index (FSFI) questionnaire before and after surgery. The cosmetic result was investigated by administering the Patient Scar Assessment Questionnaire and Scoring System (PSAQ). RESULTS AND LIMITATIONS A total of 59 HTNNs and 3 PTNNs were successfully performed. One patient was converted to open surgery because of injury to the inferior vena cava. The mean operative time was 130min (range: 100-260min) for HTNN and 193min (range: 180-210min) for PTNN. The mean estimated blood loss was 150ml. The mean postoperative hospital stay was 7.4 d. Forty-eight patients completed the FSFI questionnaire, and analysis did not show differences in FSFI scores before and after surgery. The better cosmetic results were confirmed by the PSAQ score. CONCLUSIONS HTNN is feasible and safe in appropriate patients. Existing instruments are adequate for HTNN, but significant improvement is still needed. PTNN is technically challenging, but is feasible and may be performed safely. Further improvement of instruments is necessary for PTNN. Clinical investigation in comparison to the established techniques should take place to evaluate the outcome of technique. PATIENT SUMMARY Pure transvaginal natural orifice transluminal endoscopic nephrectomy (PTNN) is technically challenging but feasible and may be performed safely. Further improvements in instruments are necessary for PTNN.

Transumbilical Multiport Laparoscopic Nephrectomy with Specimen Extraction through the Vagina

Objectives: To report our initial experience with transumbilical multiport laparoscopic nephrectomy (TMLN) with transvaginal specimen extraction. Patients and Methods: Between January and July 2010, 5 married and parous female patients were submitted to TMLN with transvaginal specimen extraction in our center. All data referring to patient demographics, surgery, pathology and perioperative outcomes were recorded. Sexual function was assessed with the Female Sexual Function Index questionnaire before and after surgery. The cosmetic result was investigated by administering the Patient Scar Assessment Questionnaire and Scoring System (PSAQ). Results: All procedures were completed successfully. The mean operative time was 136 min (range 110-160 min, standard deviation [SD] 20.7). The mean estimated blood loss was 66 ml (range 40-100 ml, SD 24.1). The mean postoperative hospitalization stay was 4.8 days (range 4-6 days, SD 0.8). All patients reported unaltered sexual function after surgery. The better cosmetic results were confirmed by the PSAQ score. Conclusions: TMLN with transvaginal specimen extraction is feasible and safe for married and parous female patients. This technique is a natural evolution towards natural orifice transluminal endoscopic surgery (NOTES). By acting as an intermediate-type procedure, it provides a bridge through which NOTES may ultimately gain clinical acceptance.

Pure transvaginal natural orifice translumenal endoscopic surgery for renal cyst decortication: Report of initial five cases

To present our initial experience with pure transvaginal natural orifice translumenal endoscopic surgery renal cyst decortication.

Suprapubic-assisted laparoendoscopic single-site surgery (LESS) in urology: our experience.

To report our experience with suprapubic‐assisted laparoendoscopic single‐site surgery (SA‐LESS) in urology.

MiR-193a-3p functions as a tumour suppressor in human aldosterone-producing adrenocortical adenoma by down-regulating CYP11B2

The mechanism of aldosterone‐producing adrenocortical adenoma (APA) pathogenesis and the role of microRNAs (miRNAs) in APA pathogenesis have not been completely clarified. We examined the expression and function of miR‐140‐3p, miR‐193a‐3p and miR‐22‐3p, which have binding sites in CYP11B2. Expression of miRNAs and CYP11B2 mRNA was measured by quantitative reverse transcription PCR (qRT‐PCR). Cell proliferation was monitored by colorimetric analysis, and cell apoptosis and cell cycle progression were analysed by flow cytometry. ELISA was carried out to detect aldosterone levels in cell culture supernatants. Luciferase reporter assays, qRT‐PCR and Western blotting were performed to identify CYP11B2 as a target of miR‐193a‐3p. Of the three miRNAs examined, miR‐193a‐3p exhibited a significant decrease and CYP11B2 mRNA exhibited a significant increase in expression in APA compared with adjacent normal adrenal gland tissue. Transfection of miR‐193a‐3p mimic into the human adrenocortical cell line H295R showed that elevated miR‐193a‐3p expression inhibits proliferation and aldosterone secretion, induces G1‐phase arrest and promotes apoptosis in H295R cells. Furthermore, in luciferase reporter assays, overexpression of miR‐193a‐3p in H295R cells significantly reduced the luciferase activity of the wild‐type CYP11B2 3ʹ‐UTR construct, which could be reversed by mutation of the miR‐193a‐3p‐binding site. Moreover, miR‐193a‐3p overexpression downregulated CYP11B2 mRNA and protein expression. Finally, overexpression of CYP11B2 diminished the effects of miR‐193a‐3p on H295R cells. Taken together, our results suggest that CYP11B2 levels may be modulated by miR‐193a‐3p in APA, which could explain, at least partially, why downregulation of miR‐193a‐3p during APA formation may promote cell growth and suppress apoptosis.

Transvaginal NOTES Nephrectomy

Natural orifice translumenal endoscopic surgery (NOTES) nephrectomy has been reported by several centers. Between May 2010 and January 2015, we have performed 178 transvaginal NOTES nephrectomies. Eighteen of these underwent pure transvaginal NOTES nephrectomies. At first, two umbilical trocars and one transvaginal trocar were used during the procedure. Then, one umbilical trocar and a transvaginal multi-instrument access port were used. At last, there was no umbilical trocar. Dissection was performed according to the method of a standard laparoscopic transabdominal nephrectomy. The specimen was placed inside a homemade bag and removed through an extended incision at the posterior vaginal fornix. Transvaginal NOTES nephrectomy was successfully completed in 172 patients. Five patients were converted to open surgery, and 1 patient was converted to suprapubic-assisted laparoendoscopic single-site surgery. At a mean range follow-up of 51.8 (10–69) months, the posterior colpotomy incision healed well, and the scars were nearly invisible on the abdominal wall. The female sexual function index (FSFI) questionnaire showed that transvaginal NOTES nephrectomy did not affect the female sexual function. Therefore, NOTES nephrectomy using the vagina as an entry point to the peritoneal cavity is very promising.

Prospective randomized comparison of transumbilical two-port laparoscopic and conventional laparoscopic varicocele ligation.

We have established a novel method named transumbilical two-port laparoscopic varicocele ligation (TTLVL) for varicocele, which is still needed to evaluate. In this study, 90 patients with left idiopathic symptomatic varicoceles of grades II-III according to the Dubin grading system were randomly assigned to TTLVL (n = 45) and conventional laparoscopic varicocele ligation (CLVL) (n = 45). The demographic, intraoperative, postoperative, and follow-up data were recorded and compared between the two groups. All the procedures in the two groups were completed successfully with no intraoperative complications and no conversions to open surgery. No significant difference was found in the operative time, resuming ambulation, bowel recovery, postoperative hospital stay, and postoperative resolution of scrotal pain between the two groups (P > 0.05). However, the postoperative mean visual analog pain scale scores for TTLVL group were all less at 24 h, 48 h, 72 h, and 7 days postoperatively compared to CLVL (P = 0.001, 0.010, 0.006, and 0.027, respectively). The mean patient scar assessment questionnaire score in postoperative month 3 was 29.7 for TTLVL group compared with 32.1 for CLVL group (P < 0.001). There was no testicular atrophy observed in both groups during the follow-up period. The study shows that TTLVL is a safe, feasible, and effective minimally invasive surgical alternative to CLVL for the treatment of varicocele. Compared with CLVL, TTLVL may decrease postoperative pain and improve the cosmetic outcomes.