Rupture of sinus of Valsalva aneurysm: Two case reports and a concise review of the literature

Background

The rupture of sinus of Valsalva aneurysm (RSoVA) is a rare disorder that affects the integrity of the cardiovascular system, disrupting its dynamics and resulting in a variety of manifestations. In this report, we discuss two cases of RSoVA that we encountered and review similar cases reported in the literature.

Livin和PTEN在肾细胞癌中的表达及其临床意义

目的研究Livin和PTEN在肾细胞癌（RCC）中的表达意义及两者的关系。方法应用免疫组化检测44例肾细胞癌组织和10例正常肾组织Livin和PTEN蛋白的表达情况。结果 Livin蛋白在肾细胞癌组织中的表达率为47.7%（21/44）,在正常肾组织中不表达,两者有统计学意义（P〈0.05）;在肾细胞癌中,Livin的表达与临床分期、淋巴结转移均显著相关（P〈0.05）;PTEN蛋白在肾癌组织中的表达率为38.6%（17/44）,在正常肾组织中表达率为100.0%,两者有统计学意义（P〈0.05）;在肾细胞癌中,PTEN的表达与临床分期、组织分级、淋巴结转移均显著相关（P〈0.05）;Livin在肾细胞癌组织中异常高表达,而PTEN低表达,两者表达呈显著负相关性（γ=-0.326,P〈0.05）。结论 Livin和PTEN可能成为RCC的重要诊断指标和基因治疗靶点。     

Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm

OBJECTIVE

To evaluate our early experience with neoadjuvant therapy (sunitinib or sorafenib) in advanced renal cell carcinoma (RCC), to explore the effect on both tumour biology and potential for downstaging advanced tumours, as systemic therapy for RCC has historically resulted in little if any primary tumour response, but recent experience with targeted therapy suggests otherwise.

PATIENTS AND METHODS

The preliminary experience with neoadjuvant therapy for the surgical management of RCC was reviewed at two large referral centres. Several unique patients were identified who had a novel response to systemic therapy that altered the surgical strategy.

RESULTS

Four patients who had targeted therapy before surgery are described and in whom there were effects on tumour biology not seen previously with chemotherapy and cytokine therapy. The selected patients who had neoadjuvant targeted therapy had shrinkage of a tumour thrombus in the inferior vena cava, nodal involvement, renal fossa recurrence and tumour within a solitary kidney.

CONCLUSIONS

The introduction of new molecular agents has revolutionized the treatment of patients with metastatic RCC. Responses to targeted therapy within the primary tumour, tumour thrombus, renal fossa recurrence, and lymph node metastases are novel findings not seen during treatment with immunotherapeutic‐based strategies. This might be a signal for urological surgeons to re‐evaluate the paradigm for the surgical management of advanced RCC. Potential applications are presented to encourage further investigations with targeted therapy in the neoadjuvant setting.     

Carbonic Anhydrase IX in Renal Cell Carcinoma: Implications for Prognosis,Diagnosis, and Therapy

Context

The clinical management of patients with renal cell carcinoma (RCC) remains difficult, and the development of new diagnostic, prognostic, and therapeutic tools is still required.

Objective

To review the current knowledge on the RCC-associated antigen carbonic anhydrase IX (CAIX) and provide evidence for how this antigen may aid in the clinical management of RCC.

Evidence acquisition

Clinical papers describing diagnostic, prognostic, and/or therapeutic applications of CAIX in RCC were selected from the Pubmed database. The search was manually augmented by reviewing the reference lists of articles.

Evidence synthesis

Expression of CAIX is regulated by the Von Hippel Lindau (VHL) protein (pVHL). Because of the invariable VHL mutational loss in clear-cell RCC (ccRCC) patients, CAIX expression is ubiquitous in ccRCC. Determination of CAIX expression in nephrectomy specimens of RCC patients improves prognostic accuracy; high CAIX expression appears to correlate with a favourable prognosis and a greater likelihood of response to systemic treatment for metastatic disease. Therefore, CAIX expression might be used to stratify metastatic ccRCC (mRCC) patients for systemic treatment. When incorporated into the RCC nomogram, CAIX expression seems to improve diagnostic accuracy for primary RCC as well as mRCC patients, but further evidence is required. Clinical studies with the CAIX-specific monoclonal antibody (mAb) cG250 have provided unequivocal evidence that ccRCC lesions can be imaged with radiolabeled cG250. Results are awaited of a large, randomised trial that aims to establish the value of cG250 imaging for primary RCC. The outcome of another large, placebo-controlled study is awaited to establish the usefulness of CAIX-targeted therapy in the adjuvant setting. Therapeutic trials with high-dose radiolabeled cG250 and CAIX-loaded dendritic cells in mRCC patients are still in phase 1 or 2.

Conclusions

CAIX improves diagnostic accuracy and is an attractive target for imaging of and therapy for ccRCC.     

Inflammatory Protein Serum Amyloid A1 Marks a Subset of Conventional Renal Cell Carcinomas with Fatal Outcome

Background

Conventional renal cell carcinoma (RCC) is the most common renal cancer. As the metastatic conventional RCC is practically incurable, there is a need for markers to estimate the tumour aggressiveness.

Objective

To identify and characterise new marker(s) associated with the poor prognosis of conventional RCC.

Design, Setting, and Participants

RNA from 24 conventional RCCs was analysed for global gene expression by Affymetrix U133 Plus 2.0 arrays. Tissue microarrays containing 224 renal tumours including 87 conventional RCCs were used for immunohistochemistry. Cell lines HD2, HD48, HA344 and HA465 established in our laboratory were used for invasion assay and zymography.

Measurements

Serum amyloid A 1 (SAA1) was found to be upregulated in conventional RCCs and it has been analysed by quantitative RT-PCR and immunohistochemistry on TMAs to establish the correlation between SAA1 protein expression and patient survival by uni and multivariate analysis. The effect of SAA1 on tumour cell behaviour in vitro has also been examined by invasion assay and zymography.

Results and Limitations

SAA1 RNA is expressed in conventional RCC samples of patients with poor prognosis. Immunohistochemistry of 72 conventional RCCs with a 5 yr follow up showed a correlation between SAA1 expression and the clinical outcome of disease. Stimulation of conventional RCC cell lines with recombinant SAA1 increased the expression of metalloproteinase (MMP)-9 and the invasive potential of tumour cells. Limitation of the study is a relatively small number (72) of patients having follow up.

Conclusion

SAA1 seems to be a useful marker to estimate the prognosis of conventional RCCs.     

Prognostic ability of simplified nuclear grading of renal cell carcinoma

BACKGROUND: The Fuhrman grading system is an established predictor of survival in patients with renal cell carcinoma (RCC). The predictive accuracy of various Fuhrman grading schemes was tested with the intent of improving the prediction of RCC-specific survival (RCC-SS). METHODS: The analyses targeted 5453 patients from 14 institutions. Univariable, multivariable, and predictive accuracy analyses addressed RCC-SS. The statistical significance of the gain in predictive accuracy was quantified with the Mantel-Haenszel test. RESULTS: The median follow-up time was 4.5 years. In both univariable and multivariable analyses, Fuhrman grade achieved independent predictor status regardless of the coding scheme. When Fuhrman grade was not considered in multivariable analyses, the predictive accuracy was 83.8%. Addition of Fuhrman grade to the multivariable model resulted in predictive accuracy gains of 0.8% for all 3 grading schemes tested. CONCLUSION: Fuhrman grade must to be considered when RCC-SS is assessed. However, modified or conventional Fuhrman grading schemes perform equally well as the conventional grading system.     

人肾细胞癌原位移植裸鼠肺转移模型的建立

目的：建立肾癌原位肺转移动物模型,研究动物模型肾癌移植瘤和肺部转移瘤的生长情况,确定肾癌肺转移的初始时间。方法：人肾癌细胞株SN12-PM6种植于裸鼠右肾实质内,连续观察裸鼠肾脏肿瘤及肺部转移瘤的生长情况。所有采用标本10％甲醛溶液固定,常规石蜡包埋,切片HE染色后分析结果。结果：肾脏的成瘤率为100％（39／39）,第5周开始观察到肿瘤的肺转移灶,肺部转移率50％（4／8）,在随后3周其肺部转移率分别为75％（3／4）,100％（8／8）和100％（7／7）,肠道、肝脏、脾脏等脏器未发现明显的转移灶。结论：成功构建人肾细胞癌原位裸鼠肺转移动物模型,为肾癌特别是肾癌肺部转移提供了一个非常理想的研究模型。