Xiaobing Ju

Laparoscopic Partial Nephrectomy With Segmental Renal Artery Clamping: Technique and Clinical Outcomes

BACKGROUND Warm ischemic injury is one of the most important factors affecting renal function in partial nephrectomy (PN). The technique of segmental renal artery clamping emerges as an alternative to conventional renal artery clamping for renal hilar control. OBJECTIVE To evaluate the feasibility and efficiency of laparoscopic PN (LPN) with segmental renal artery clamping in comparison with the conventional technique. DESIGN, SETTING, AND PARTICIPANTS A total of 75 patients underwent LPN from June 2007 to November 2009. All patients had T1a or T1b tumor in one kidney and a normal contralateral kidney. Thirty-seven patients underwent surgeries with main renal artery clamping, and 38 underwent surgeries with segmental artery clamping. INTERVENTION All procedures were performed by the same laparoscopic surgeon. MEASUREMENTS Blood loss, operation time, warm ischemia (WI) time, and complications affected renal function before and after operation were recorded. RESULTS AND LIMITATIONS All LPNs were completed without conversion to open surgery or nephrectomy. The novel technique slightly increased WI time (p<0.001) and intraoperative blood loss (p=0.006), while it provided better postoperative affected renal function (p<0.001) compared with the conventional technique. The total complication rate was 12%. Among the 38 cases where segmental renal artery clamping was performed, 7 had to convert to the conventional method. Tumor size and location influenced the number of clamped segmental arteries. Long-term postoperative renal function is still awaited. CONCLUSIONS LPN with segmental artery clamping is safe and feasible in clinical practice. It minimizes the intraoperative WI injury and improves early postoperative affected renal function compared with main renal artery clamping.

Precise Segmental Renal Artery Clamping Under the Guidance of Dual-source Computed Tomography Angiography During Laparoscopic Partial Nephrectomy

BACKGROUND Minimizing warm ischemic (WI) injury is one technical focus of partial nephrectomy (PN). Inducing regional ischemia in the tumor area by clamping segmental renal arteries has become an alternative method to decrease WI injury. OBJECTIVE To study the technical feasibility of precise segmental artery clamping under the guidance of dual-source computed tomography (DSCT) angiography during laparoscopic partial nephrectomy (LPN) and to analyze the factors affecting surgical outcomes. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 125 patients with unilateral kidney tumor treated from December 2009 to November 2011 with a mean follow-up of 18 mo. INTERVENTION All patients received retroperitoneal LPN with the feeding segmental arteries precisely clamped. Most of the target branches were dissected close to the hilar parenchyma. The tumor was excised after precise clamping and renorrhaphy was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable logistic regression analyses were performed for categorical variables, and continuous variables were analyzed by linear regression. RESULTS AND LIMITATIONS The target branches were isolated and clamped successfully in all patients without clamping the main renal artery. Median estimated blood loss (EBL) was 200 ml, and nine patients received blood transfusion. The accuracy of feeding artery orientation by DSCT angiography reached 93.6%. Tumor size, location, and growth pattern independently influenced the number of clamped branches. The number of clamped branches was significantly associated with postoperative renal function and EBL. Limitations of this study include its retrospective nature and that data are from a single-surgeon series. CONCLUSIONS The precise segmental artery clamping technique under the guidance of DSCT angiography is feasible and efficient to excise the tumor and to protect the normal parenchyma. The number of clamped branches is associated with tumor characteristics and can predict EBL and loss of renal function.

miR-152 controls migration and invasive potential by targeting TGFα in prostate cancer cell lines†

MicroRNAs (miRNAs) are a class of short non‐coding RNAs that function in diverse biological processes. Aberrant miR‐152 expression has been frequently reported in various malignant tumors. However, the mechanism of miR‐152 in prostate cancer (PCa) remains unclear. This study aims to determine the function of miR‐152 in PCa cells and identify the novel molecular targets regulated by miR‐152.

miR-154 inhibits EMT by targeting HMGA2 in prostate cancer cells.

Epithelial–mesenchymal transition (EMT) is a crucial process that plays an important role in the invasion and metastasis of human cancers. High-mobility group AT-hook 2 (HMGA2) has been found to be involved in the EMT program, with its aberrant expression having been observed in a variety of malignant tumors. However, the mechanisms regulating HMGA2 expression remain incompletely understood. The objective of this study was to investigate whether mir-154 plays a critical role in EMT by regulating HMGA2. The expression levels of HMGA2 were examined in four samples of prostate cancer (PCa) tissue and adjacent non-tumorous tissue by Western blot analysis. The effects of forced expression of miR-154 or HMGA2 knockdown on PCa cells were evaluated by cell migration and invasion assays and Western blot analysis. HMGA2 was upregulated in the PCa tissue samples compared with the adjacent normal ones. Forced expression of miR-154 or HMGA2 knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro and inhibited EMT gene expression, increased the levels of E-cadherin, an epithelial marker, and decreased the levels of vimentin, a mesenchymal marker. HMGA2 is a direct target gene of miR-154 by dual-luciferase reporter assay. Our findings suggest that miR-154 plays a role in regulating EMT by targeting HMGA2. Understanding the targets and regulating pathways of miR-154 may provide new insights into the underlying pathogenesis of PCa.

Application of a Vasculature Model and Standardization of the Renal Hilar Approach in Laparoscopic Partial Nephrectomy for Precise Segmental Artery Clamping

BACKGROUND Clamping the segmental renal artery instead of the main renal artery during nephron-sparing surgery is a promising technique to decrease warm ischemia injury. Understanding vasculature characteristics and adopting an appropriate hilar approach to segmental arteries are essential to the technique. OBJECTIVE To study the role of the vasculature model and to standardize the renal hilar approach in segmental renal artery dissection during laparoscopic partial nephrectomy (LPN). DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis of a consecutive series of 82 patients who underwent LPN with a precise clamping technique from December 2009 to June 2011 with a mean follow-up of 20 mo. SURGICAL PROCEDURE Three-dimensional dynamic renal vascular models were established based on dual-source computed tomographic angiography. Clamping number, clamping position, and a different hilar approach accessing target segmental arteries were determined preoperatively. Target arteries were dissected and clamped based on the model. Tumor excision and renorrhaphy were performed under regional parenchymal ischemia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Renal vascular characteristics and surgical outcomes were analyzed. The outcomes among different surgical approaches were compared using one-way analysis of variance test or Fisher exact test. RESULTS AND LIMITATIONS All surgeries were performed successfully without converting to main renal artery clamping or radical nephrectomy. The median operative time was 90 min, and the mean clamping time was 24 min. The median estimated blood loss (EBL) was 200 ml, and six patients received blood transfusions. Five patients had hematuria without any intervention. One patient had a postoperative hemorrhage and received selective embolization intervention. Statistical analysis showed that appropriate surgical approaches chosen from the models led to comparable operative times, EBL, and complication rates. The limitation of the study lies on its retrospective feature. CONCLUSIONS A renal vasculature model provides effective orientation for a precise clamping technique. A standardized hilar approach based on the model optimizes the surgical procedure and leads to satisfactory surgical outcomes.

miR-134 Functions as a Tumor Suppressor in Cell Proliferation and Epithelial-to-Mesenchymal Transition by Targeting KRAS in Renal Cell Carcinoma Cells

Aberrant microRNAs (miRNAs) are reported to contribute to the pathogenesis of most human malignancies. The miRNA, miR-134, has been found to be downregulated in renal cell carcinoma (RCC), but its function in the disease is unknown. The aims of this study were to detect the expression of miR-134 in human RCC samples and explore its function in RCC cell lines. Real-time qualitative polymerase chain reaction (qPCR) was used to quantify miR-134 in human RCC samples. Assays for cell cycle, viability, migration, and invasion were performed to assess the phenotypic changes in RCC cells. A luciferase reporter assay was carried out to confirm whether KRAS (Kirsten rat sarcoma viral oncogene homolog) is a direct target of miR-134. Western blot was used to identify the potential signaling pathways that had an impact on RCC cell growth and alterations of markers for epithelial-mesenchymal transition (EMT), which affected metastasis by miR-134. miR-134 was found to be downregulated in RCC samples (p<0.05), while overexpression of miR-134 suppressed proliferation (p<0.05) by triggering G1/G0 cell cycle arrest (p<0.05). Forced expression of miR-134 could also inhibit migration (p<0.05) and invasion (p<0.05) by blocking EMT in RCC cell lines. KRAS was identified as a target of miR-134, and miR-134 may act as a tumor suppressor through the KRAS-related MAPK/ERK pathway other than PI3K/AKT signaling. Thus, miR-134 may function as a tumor suppressor in cell proliferation and EMT by targeting KRAS in RCC cells.

Laparoscopic Radical Nephrectomy and Inferior Vena Cava Thrombectomy in the Treatment of Renal Cell Carcinoma

BACKGROUND Radical nephrectomy with inferior vena cava (IVC) thrombectomy is the preferred treatment for renal cell carcinoma (RCC) with IVC thrombus. However, IVC thrombectomy using a laparoscopic approach has not been reported for high-level thrombi. OBJECTIVE To describe the surgical technique for laparoscopic IVC thrombectomy in patients with different thrombus levels and to assess its safety and feasibility. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of medical records for 11 patients with right-side RCC, including six patients with level II IVC thrombus and five patients with level IV thrombus. SURGICAL PROCEDURE Laparoscopic thrombectomy for level II thrombus was performed after clamping the infrarenal IVC, left renal vein, and infrahepatic IVC. Laparoscopic thrombectomy and thoracoscope-assisted open atriotomy for level IV thrombus were performed after establishing cardiopulmonary bypass and clamping the infrarenal IVC, left renal vein, and hepatoduodenal ligament. MEASUREMENTS The intraoperative variables, postoperative complications, and surgical outcomes were assessed. RESULTS AND LIMITATIONS The median operative time was 210min. The median IVC clamping time for patients with level II and level IV thrombus was 16.5 and 31min, respectively. The median estimated blood loss was 510ml, and no major intraoperative or postoperative complications occurred. One patient with level IV thrombus died of brain metastasis 6 mo after the operation, and the remaining ten patients had no local recurrence or distant metastasis during a median follow-up period of 31 mo. CONCLUSIONS Laparoscopic IVC thrombectomy for level II thrombus and well-selected level IV thrombus may be a safe and technically feasible alternative to open surgery. PATIENT SUMMARY We studied the treatment of patients with an inferior vena cava thrombus at different levels using a laparoscopic approach. This technique was safe and feasible in well-selected patients.

A potentially functional polymorphism in the promoter region of miR-34b/c is associated with renal cell cancer risk in a Chinese population

Members of the miR-34 family have been shown to be transcriptional targets of the tumour suppressor gene P53. Aberration expression of miR-34 impairs p53-mediated cell cycle arrest and apoptosis. A single nucleotide polymorphism T > C (rs4938723) located within the CpG island in the promoter region of pri-miR-34b/c may affect its expression and has been suggested to influence cancer risk. In this study, we genotyped rs4938723 using the TaqMan method to explore the relationship between this polymorphism and the risk of renal cell cancer (RCC) in a case-control study of 710 RCC patients and 760 control subjects. We found that individuals carrying the CC genotype had a significantly increased RCC risk compared with those with TT or TT/TC genotypes [odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.06-2.21 for CC vs. TT and OR = 1.48, 95% CI = 1.05-2.10 for CC vs. TT/TC). Furthermore, the increased risk was more evident in the subgroups of older subjects (OR = 1.80, 95% CI = 1.08-3.01), males (OR = 1.64, 95% CI = 1.08-2.51), smokers (OR = 2.07, 95% CI = 1.16-3.69) and drinkers (OR = 1.94, 95% CI = 1.01-3.73), although no interaction between rs4938723 and these characteristics was observed. Twenty-seven normal tissues adjacent to tumour were used to evaluate the association between the expression level of miR-34b/c and the polymorphism, which revealed higher expression levels of miR-34b/c in normal renal tissues with TT+TC genotypes than in those with CC genotypes (P < 0.01). Furthermore, a luciferase gene assay in 293-T cells showed that the luciferase activities with rs4938723 T allele are higher than that with C allele (P < 0.05). These results suggest that the miR-34b/c rs4938723 C allele may increase susceptibility to RCC by decreasing the activity of pri-miR-34b/c promoter.

A functional variant in the MTOR promoter modulates its expression and is associated with renal cell cancer risk.

Background The mTOR signaling pathway plays a crucial role in the carcinogenesis of renal cell cancer (RCC). We sought to investigate the influence of genetic variations in the mTOR pathway-related genes on the risk of RCC. Methods We genotyped 8 potentially functional polymorphisms in AKT1, AKT2, PTEN and MTOR genes using the TaqMan method in a case-control study of 710 RCC patients and 760 cancer-free subjects. Unconditional logistic regression, adjusted for potential confounding factors, was used to assess the risk associations. We then examined the functionality of the important polymorphisms. Results Of the 8 polymorphisms, after adjusting for multiple comparisons, we found a significant association between one variant (rs2295080) in the promoter of MTOR and reduced RCC risk (P = 0.005, OR = 0.74, 95%CI = 0.59–0.91, TG/GG vs. TT). Another variant (rs701848) in the 3′UTR region of PTEN was associated with increased RCC risk (P = 0.014, OR = 1.45, 95%CI = 1.08–1.96, CC vs. TT); however, the association was not significant after adjusting for multiple comparisons. Furthermore, we observed lower MTOR mRNA levels in the presence of the rs2295080G allele in normal renal tissues. The luciferase reporter assay showed that the rs2295080G allele significantly decreased luciferase activity. No other significant association between the selected polymorphisms and RCC risk was observed. Conclusions Our results suggest that the functional MTOR promoter rs2295080 variant affects RCC susceptibility by modulating the endogenous MTOR expression level. The risk effects and the functional impact of the MTOR rs2295080 variant need further validation.

Functional promoter -31G>C variant in survivin gene is associated with risk and progression of renal cell cancer in a Chinese population.

Background Survivin is an inhibitor of apoptosis protein and is involved in the occurrence and progression of human malignancies. Recently, a functional polymorphism (−31G>C, rs9904341) in the promoter of survivin has been shown to influence its expression and confer susceptibility to different types of cancer. The present study was aimed to investigate whether the polymorphism also influences susceptibility and progression of renal cell cancer (RCC) in a Chinese population. Methods We genotyped this polymorphism using the TaqMan assay in a case-control study comprised of 710 RCC patients and 760 controls. The logistic regression was used to assess the genetic association with occurrence and progression of RCC. Results Compared with the genotypes containing G allele (GG and GC), we found a statistically significant increased occurrence of RCC associated with the CC genotype [P = 0.006, adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08–1.76]. The polymorphism was associated with risk of developing advanced stage (OR = 2.02, 95%CI = 1.34–3.07) and moderately differentiated (OR = 1.75; 95%CI = 1.20–2.54) RCC. Furthermore, the patients carrying the CC genotype had a significantly greater prevalence of high clinical stage disease (Ptrend = 0.003). Similar results were also observed when we restricted the analysis to clear cell RCC, a major histological type of RCC. Conclusions Our results suggest that the functional −31G>C polymorphism in the promoter of survivin may influence the susceptibility and progression of RCC in the Chinese population. Large population-based prospective studies are required to validate our findings.