A Case of Metastatic Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome-Associated Renal Cell Carcinoma Treated with a Sequence of Axitinib and Nivolumab Following Cytoreductive Nephrectomy

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) associated renal cell carcinoma (RCC) is an aggressive form of type 2 papillary RCC caused by deficiency of the fumarate hydratase gene. For patients with metastatic disease, no standard treatment has been established with dismal prognosis. We report a case of metastatic HLRCC-associated RCC in a 65-year-old Japanese male whose clinical features mimicked advanced renal pelvic cancer. A durable response was achieved with a sequence of axitinib and nivolumab after cytoreductive and diagnostic nephrectomy. Their potential therapeutic roles in the management of metastatic HLRCC-associated RCC have been discussed based on its molecular and biological backgrounds

What Affects the Visualization of Prostate Cancer Using MRI in Patients Treated with RARP?

Aim：To assess the index lesions（the largest and clinically significant ones）in cases of surgically confirmed prostate cancer（PCa）using a multi-parametric MRI at 3 tesla and to evaluate the relationships between the clinical-pathological features of index PCas and cancer visualization. Materials and Methods：This retrospective study included 67 patients who had undergone roboticassisted radical prostatectomy. Two radiologists reviewed the MRIs（axial and coronal T2-weighted imaging, diffusion-weighted imaging（DWI）with apparent diffusion coefficient mapping and dynamic contrast enhancement MRI（DCEI））. The patients were divided into 4 groups as follows：detected on all 3 sequences（A）, on 2 of 3 sequences（B）, on 1 of 3 sequences（C）, and on none of them（D）. In all groups, all PCa characteristics were assessed, including the PSA level, Grade Group（GG）based on the Gleason score（GS）, the D’Amico criteria, and the maximum tumour length（TL）of the biopsy specimen. Results：Of the 67 patients, 16 were high-risk according to the D’Amico criteria, and 15 of these 16 high-risk patients（94％）belonged to either Group A or Group B. In addition, the mean TL and GG were longer and higher, respectively, in Group A than in the other groups（p＜0.05）. Furthermore, in Group B, 3 of the 4 high-risk patients（75％）were detected using DWI and DCEI. The lesions detected using DWI and DCEI had higher GSs and were in a higher GG. Conclusion：PCas of pathologically higher grades and clinically higher risk were more readily detectableusing multiple parameters

Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer

<p>Abstract</p> <p>Background</p> <p>Lymphovascular invasion (LVI) and lymph node metastasis are conventional pathological factors associated with an unfavorable prognosis of urothelial carcinoma of the upper urinary tract (UC-UUT), but little is known about the molecular mechanisms underlying LVI and nodal metastasis in this disease. Rac1 small GTPase (Rac1) is essential for tumor metastasis. Activated GTP-bound Rac1 (Rac1 activity) plays a key role in activating downstream effectors known as Pak (21-activated kinase), which are key regulators of cytoskeletal remolding, cell motility, and cell proliferation, and thus have a role in both carcinogenesis and tumor invasion.</p> <p>Methods</p> <p>We analyzed Rac1 activity and Pak1 protein expression in matched sets of tumor tissue, non-tumor tissue, and metastatic lymph node tissue obtained from the surgical specimens of 108 Japanese patients with UC-UUT.</p> <p>Results</p> <p>Rac1 activity and Pak1 protein levels were higher in tumor tissue and metastatic lymph node tissue than in non-tumor tissue (both <it>P </it>< 0.0001). A high level of Rac1 activity and Pak1 protein expression in the primary tumor was related to poor differentiation (<it>P </it>< 0.05), muscle invasion (<it>P </it>< 0.01), LVI (<it>P </it>< 0.0001), and lymph node metastasis (<it>P </it>< 0.0001). Kaplan-Meier survival analysis showed that an increase of Rac1 activity and Pak1 protein was associated with a shorter disease-free survival time (<it>P </it>< 0.01) and shorter overall survival (<it>P </it>< 0.001). Cox proportional hazards analysis revealed that high Rac1 activity, Pak1 protein expression and LVI were independent prognostic factors for shorter overall and disease-free survival times (<it>P </it>< 0.01) on univariate analysis, although only Pak1 and LVI had an influence (<it>P </it>< 0.05) according to multivariate analysis.</p> <p>Conclusions</p> <p>These findings suggest that Rac1 activity and Pak1 are involved in LVI and lymph node metastasis of UC-UUT, and may be prognostic markers for this disease.</p

Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis

<p>Abstract</p> <p>Background</p> <p>Interferon-α (IFN-α) is one of the central agents in immunotherapy for renal cell carcinoma (RCC) and binds to the IFN-α receptor (IFNAR). We investigated the role of IFNAR in RCC.</p> <p>Methods</p> <p>We quantified IFNAR mRNA expression in paired tumor and non-tumor samples from the surgical specimens of 103 consecutive patients with RCC using a real-time reverse transcription polymerase chain reaction (RT-PCR), and IFNAR2 protein using Western blotting.</p> <p>Results</p> <p>The absolute level of IFNAR1 and IFNAR2 mRNAs in tumor and non-tumor tissues did not correlate with the malignant and metastatic profiles. The relative yields of the PCR product from the tumor tissue to that from the corresponding non-tumor tissue (T/N) for the expression of IFNAR mRNAs were calculated. While the T/N ratio of IFNAR1 did not correlate with any factor, a high T/N ratio of IFNAR2 correlated with poor differentiation (<it>P </it>< 0.05), local invasion (<it>P </it>< 0.001), and metastasis (<it>P </it>< 0.0001). By multivariate analysis, a high T/N ratio of IFNAR2 predicted a shortened overall survival in all cases (<it>P </it>< 0.05) and a shorter disease-free survival in those without metastasis (M0; 68 cases, <it>P </it>< 0.05). Impressively, patients with a poorer response to IFN-α treatment had a higher IFNAR2 T/N ratio than those who had a good response (P < 0.05). IFNAR2c protein expression was higher in the primary tumors in patients with metastases (M1; 35 cases) compared to those without ( P < 0.0001).</p> <p>Conclusion</p> <p>IFNAR2 is associated with the progression of RCC.</p

Single minimum incision endoscopic radical nephrectomy for renal tumors with preoperative virtual navigation using 3D-CT volume-rendering

<p>Abstract</p> <p>Background</p> <p>Single minimum incision endoscopic surgery (MIES) involves the use of a flexible high-definition laparoscope to facilitate open surgery. We reviewed our method of radical nephrectomy for renal tumors, which is single MIES combined with preoperative virtual surgery employing three-dimensional CT images reconstructed by the volume rendering method (3D-CT images) in order to safely and appropriately approach the renal hilar vessels. We also assessed the usefulness of 3D-CT images.</p> <p>Methods</p> <p>Radical nephrectomy was done by single MIES via the translumbar approach in 80 consecutive patients. We performed the initial 20 MIES nephrectomies without preoperative 3D-CT images and the subsequent 60 MIES nephrectomies with preoperative 3D-CT images for evaluation of the renal hilar vessels and the relation of each tumor to the surrounding structures. On the basis of the 3D information, preoperative virtual surgery was performed with a computer.</p> <p>Results</p> <p>Single MIES nephrectomy was successful in all patients. In the 60 patients who underwent 3D-CT, the number of renal arteries and veins corresponded exactly with the preoperative 3D-CT data (100% sensitivity and 100% specificity). These 60 nephrectomies were completed with a shorter operating time and smaller blood loss than the initial 20 nephrectomies.</p> <p>Conclusions</p> <p>Single MIES radical nephrectomy combined with 3D-CT and virtual surgery achieved a shorter operating time and less blood loss, possibly due to safer and easier handling of the renal hilar vessels.</p

Clinical Significance of Serum Soluble T Cell Regulatory Molecules in Clear Cell Renal Cell Carcinoma

To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls ( &lt; 0.05). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage ( &lt; 0.001), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels ( &lt; 0.05). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage ( &lt; 0.05), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other ( = 0.550, &lt; 0.0001). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC

Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepcidin has an important role in iron metabolism. We investigated whether hepcidin was involved in renal cell carcinoma (RCC).</p> <p>Methods</p> <p>We measured serum hepcidin-25 levels in 32 patients by liquid chromatograpy (LC)-mass spectrometry (MS)/MS, and assessed hepcidin mRNA expression in paired tumor and non-tumor tissue samples from the surgical specimens of 53 consecutive patients with RCC by real-time reverse transcription polymerase chain reaction.</p> <p>Results</p> <p>The serum hepcidin-25 level was higher in patients with metastatic RCC than nonmetastatic RCC (<it>P </it>< 0.0001), and was positively correlated with the serum interleukin-6 and C-reactive protein levels (<it>P </it>< 0.001). Expression of hepcidin mRNA was lower in tumor tissues than in non-tumor tissues (<it>P </it>< 0.0001). The serum hepcidin-25 level was not correlated with the expression of hepcidin mRNA in the corresponding tumor tissue specimens from 32 patients. Hepcidin mRNA expression in tumor tissue was correlated with metastatic potential, but not with histological differentiation or tumor stage. Kaplan-Meier analysis showed that over expression of hepcidin mRNA was related to shorter overall survival in RCC patients. Univariate analysis (Cox proportional hazards model) showed that the hepcidin mRNA level was an independent prognostic factor for overall survival.</p> <p>Conclusion</p> <p>Our findings suggest that a high serum hepcidin-25 level may indicate the progression of RCC, and that upregulation of hepcidin mRNA expression in tumor tissue may be related to increased metastatic potential.</p

A Case of Renal Angiomyolipoma with Minimal Fat Mimicking Renal Cell Carcinoma

We present a case of renal angiomyolipoma (AML) with minimal fat mimicking renal cell carcinoma(RCC). AML is composed of variable amount of fat, smooth muscle and abnormal blood vessels. In general,AML can be differentiated from RCC with great accuracy using modern radiological techniques due to thefat component of the renal mass. In the present case, the renal tumor did not demonstrate intratumoral faton radiological studies. Surgery was performed and the renal tumor was removed. Histologically, the renaltumor showed abundant muscle that occupied almost the entire lesion, which demonstrated HMB-45 antigen.The tumor was diagnosed as renal AML