The Safe Selection Of Resection Margin About Partial Nephrectomy Of Primary Renal Cell Carcinoma

BackgroundWith the development of modern medical technology, the detected rate of renal cell carcinoma is increasing year by year. In the United States, the annual incidence of renal cell carcinoma increased by 24.8% from 27,200 cases in 1990 to 36,160 cases in 2005. A recent large-scale European clinical investigation from 1987 to 2004 showed that the incidence of renal cell carcinoma accounted for about 3% of all systemic cancers and 85% of kidney tumors, where the mean annual incidence was about 7.21/100,000, and averagely increased by 2.06% yearly.Radical nephrectomy is the standard surgical treatment of renal cell carcinoma. With the popularization and spread of imaging technology such as CT, more cases of sporadic renal cell carcinoma have been detected, and most of them are primary renal cell carcinoma. In their five-year-survival follow up study of patients with 4 to 7cm renal cell carcinoma (RCC) who underwent partial nephrectomy (NSS) and radical nephrectomy (RN), Leibovich et al found that the cancer-specific survival rate was 98% and 86%, with a non-distant metastasis survival rate of 94% and 83% respectively. The stage, grade, histological type and other important pathological characteristics of RCC considered, there was no significant difference in both cancer-specific survival rate and survival rate without distant metastasis between the two groups. In the light of these findings, more and more researchers tend to use partial nephrectomy to treat primary renal cell carcinoma.ObjectiveSafe selection of the resection margin is particularly important in partial nephrectomy. An overview of the literature shows that a 1-2cm resection range is traditionally accepted as the safe margin, but many researchers come to agree that a 0.5cm resection range from the tumor capsule is safe and feasible. Why is there such a controversy? On the one hand, the mean size and volume of the kidney is relatively small in male adults measuring about 10cm long, 5cm wide and 4cm thick and weighing 134-150g, and those in female adults of the same age are even a bit smaller. Excessive resection would not only decrease effective renal units but also increase surgical difficulty and risks of complications, while inadequate resection may worry both surgeons and patients for possible tumor residuals, tumor rupture and recurrence. On the other hand, with the advent of laparoscopy as the representative of minimally invasive surgery, traditional open partial nephrectomy has been gradually replaced by laparoscopic partial nephrectomy, and the emergence of the robot surgical system with representative "Da Vinci" promotes the rapid development of surgery in terms of minimal invasion and precise direction, which calls for a higher requirement on the selection of a safe resection margin.DNA microarray and Tissue microarray have three features: high-flux, large scale, and parallelism. DNA microarray and Tissue microarray can be used for the researching of many oncogenes, anti-oncogenes, and gene-associated protein. Accordingly, to compare the differences of tumor-related genes and proteins of tumor and para-tumor normal renal tissue of different margins, can be helpful for the selecting of safe margin about partial nephrectomy of primary renal cell carcinoma.Methods1) Included in the present study were 44 patients with primary clear cell carcinoma of kidney confirmed by postoperative pathology who underwent laparoscopic radical nephrectomy in Changzheng Hospital and Shanghai 10th people's hospital between Jan 2006 and Oct 2007. Tumor tissue (A), and 0.5 cm (B), 1.0cm (C) and 2.0cm (D) para-tumor normal renal cortex were identified, measured and collected with the help of the microsurgery magnifying glass. A total of 44 groups of specimen sections with a 0.2 cm thickness were obtained.2) A total of 44 groups of specimen were fixed routinely with formalin, and paraffin-embedded for use. One group of specimen was frozen in liquid nitrogen for use.3) One group of specimen was frozen in liquid nitrogen for DNA microarray, the chip is Affymetrix Human Genome U133A 2.0 Array DNA microarray. Real time quantitive PCR was used for the proving of the results of gene chip, Including: T-cell differentiation protein (MAL) ; decorin; galectin 1 (LGALS1); transforming growth factor beta-1(TGF-β1); caveolin 1; bcl-2; secreted apoptosis related protein 2 (SARP2); secreted frizzled related protein 1 (SFRP1); S100 calcium-binding protein A2 (S100A2).4) Tissue microarrays of A/B/C/D paraffin-embedded specimens of the 44 groups were constructed in a tissue microarray instrument for use. The express difference of CD10, RCC-Ma and EMA were researched through immunohistochemistry.Results 1) DNA microarray results:(B) vs (A) up (log-ratio>2) is 1442, down(log-ratio<2) is 593; as the same, (C) vs (A) up is 1336, down is 631; (D) vs (A) up is 1259, down is 737. In the first gene group (apoptosis; oncogenes and anti-oncogenes), (B) vs (A) up (log-ratio>2) is 125, down(log-ratio<2) is 67; as the same, (C) vs (A) up is 111, down is 74; (D) vs (A) up is 103, down is 87. The difference between (A)\(B); (A)\(C) and (A)\(D) is prominent (p<0.05), and the difference is more noticeable through cluster analysis. (B)\(C)\(D) is no difference (p>0.05). The results of DNA microarray support the conclusion: The safe resection margin about partial nephrectomy of primary renal cell carcinoma is 0.5cm2) Real time quantitive PCR results:For the group of specimen was frozen in liquid nitrogen, the DNA microarray results A\B\C\D were as same as the results of Real time quantitive PCR Ap\Bp\Cp\Dp. The DNA microarray results were reliable.3) Tissue microarray results:The percentage of intensive immunostaining of CD10, RCC-Ma and EMA is as follow:CD10: A(22.72%), B(72.73%), C(75.00%), D(70.45%);EMA: A(15.91%), B(84.09%), C(86.36%), D(79.55%);RCC-Ma: A(18.18%), B(79.55%), C(77.27%), D(75.00%);The difference between (A)\(B); (A)\(C) and (A)\(D) about CD10; EMA; and RCC-Ma is prominent (p<0.05), (B)\(C)\(D) is no difference (p>0.05). The results of Tissue microarray support the conclusion: The safe resection margin about partial nephrectomy of primary renal cell carcinoma is 0.5cm Conclusions:Partial nephrectomy is very important method of the treatment about primary renal cell carcinoma. The safe resection margin about partial nephrectomy of primary renal cell carcinoma is 0.5cm.