[A Retrospective Study on the Malignancies after Renal Transplantation].

Detection of post-transplant malignant tumors and the analysis of the associated risk factors is important for monitoring the progress after renal transplantation. In this study, we retrospectively examined the medical records of 298 patients who underwent renal transplantation at two facilities in Nagasaki Prefecture (Nagasaki University Hospital and National Hospital Organization Nagasaki Medical Center). Of the 298 patients, 45 (15.1%) patients had developed malignant tumors with 50 lesions. The most common type of malignant tumor was skin cancer (eight patients; 17.8%), followed by renal cancer (six patients; 13.3%), and pancreatic cancer and colorectal cancer, (four patients; 9.0% each). Five patients (11.1%) had multiple cancers, four of whom had skin cancer. The cumulative incidence within 10 and 20 years after renal transplantation was 6.0 and 17.9%, respectively. Univariate analysis identified age at transplantation and administration of cyclosporine and rituximab as risk factors, while multivariate analysis identified age at transplantation and administration of rituximab as independent factors. The administration of rituximab was associated with the development of malignant tumors. However, further investigation is required to establish the association with post-transplant malignant neoplasms.

De novo minimal change disease after ABO-incompatible kidney transplantation.

We report the clinical and pathological findings of a case of de novo minimal change disease (MCD) after ABO-incompatible living kidney transplantation. A 62-yr-old man with end-stage renal disease associated with type I diabetes received ABO-incompatible kidney transplantation from his 58-yr-old wife. Although allograft function was excellent immediately after surgery, massive proteinuria (35 g/d) appeared on post-transplantation day 5. After the allograft biopsy taken on post-transplantation day 6, he was treated with 12 cycles of plasma exchange, but the nephrotic-range proteinuria showed no remission. The biopsy specimen showed no significant pathological findings on light microscopy, but electron microscopy showed diffuse effacement of podocyte foot processes. Based on the diagnosis of de novo MCD, the patient received intravenous methylprednisolone pulse therapy, followed by high-dose steroid maintenance therapy. The steroid therapy induced complete remission of nephrotic syndrome and stable allograft function immediately, which was also maintained at one yr after the transplantation.

Prediction of Nonadherence and Renal Prognosis by Pre-Transplantation Serum Phosphate Levels.

BACKGROUND Identifying characteristics of patients at high risk of poor adherence before transplantation would be advantageous. However, the optimal approach for characterizing such patients remains unknown. We aimed to evaluate the association between factors for hemodialysis nonadherence and post-transplant renal prognosis. We hypothesized that these factors would influence post-transplantation adherence and worsen renal prognosis. MATERIAL AND METHODS We reviewed patients on hemodialysis who underwent kidney transplantation at our hospital between 2000 and 2017 to identify risk factors associated with poor prognosis. The patients' background and pre-transplantation data, known hemodialysis nonadherence factors, serum phosphate and potassium levels, and interdialytic weight gains were evaluated. The primary endpoint was renal death. We also evaluated the fluctuation of calcineurin inhibitor concentration and weight gain after transplantation. RESULTS Seventy-seven patients were eligible, and the mean observational period was 83.2 months (standard deviation, 50.5). Thirteen patients reached the endpoint. Cox proportional hazards regression analysis showed that pre-transplantation serum phosphate level was a risk factor for renal death (p<0.05), while serum potassium levels and weight gain were not. In addition, fluctuation of calcineurin inhibitor concentration was observed in patients with higher phosphate levels before transplantation (p=0.03). Weight gain after transplantation was not associated with the hemodialysis nonadherence factors. CONCLUSIONS High pre-transplantation serum phosphate levels are considered to represent poor drug adherence and/or an unhealthy lifestyle. Patient education that conveys the importance of adhering to medications and provides nutritional guidance is crucial for improving post-transplantation renal prognosis.

Expression of matrix metalloproteinase-7 on cancer cells and tissue endothelial cells in renal cell carcinoma: prognostic implications and clinical significance for invasion and metastasis.

PURPOSE: The expression of matrix metalloproteinase-7 (MMP-7) correlates with the malignant potential of various tumors and patient survival. We investigated the clinical and prognostic significance of MMP-7 expression in cancer cells and endothelial cells in human renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: We reviewed tissue samples of 156 patients with RCC who had undergone radical operation. MMP-7 expression was examined by immunohistochemistry. Sections containing MMP-7-positive vessels were also stained for CD34. The density of MMP-7-positive vessels was determined by a computer-aided image analysis system. Multivariate analysis was done to assess relevant variables for invasion, metastasis, and cause-specific survival. RESULTS: The proportion of MMP-7-expressing tumor cells were significantly higher (P < 0.001) than that of normal cells. MMP-7-positive vessels were considered blood vessels based on staining for CD34, and their density was increased in tumor areas. The proportion of MMP-7-expressing cancer cells and density of MMP-7-positive vessels correlated with grade, pathologic tumor stage, and metastasis. Multivariate analysis showed that MMP-7 expression on cancer cells correlated with pathologic tumor stage only, whereas MMP-7-positive vessel density correlated with metastasis only. The elevated status of MMP-7 in cancer tissues was an independent predictor for cause-specific survival (odds ratio, 8.61; P = 0.040) by multivariate analysis. CONCLUSIONS: Our results showed that MMP-7 influences tumor progression by regulating invasion and angiogenesis. Multivariate analysis showed that MMP-7 status of cancer tissues was strong predictor of poor prognosis. Our results suggest that MMP-7 targeting treatment may be a potential target against RCC.

Expression of matrix metalloproteinase-10 in non-metastatic prostate cancer: Correlation with an imbalance in cell proliferation and apoptosis.

Matrix metalloproteinases (MMPs) are associated with cell invasion under various physiological and pathological conditions. Among MMPs, MMP-10 is reported to correlate with a high pT stage and progression in a variety of cancer types. However, the clinical and pathological significance of MMP-10 in human prostate cancer tissues remains unclear. This study aimed to clarify the role of MMP-10 in non-metastatic prostate cancer. Sixty-three specimens were obtained by radical prostatectomy. MMP-10 expression, Ki-67, CD34 and apoptotic cells were examined using an immunohistochemical technique and the terminal deoxynucleotidyl transferase-mediated nick end-labeling method. The proliferation index (PI), apoptotic index (AI), microvessel density (MVD) and cell renewal index (CRI=PI/AI) were calculated. The relationship between MMP-10 expression and clinicopathological features, as well as PI, AI, MVD and CRI were investigated. MMP-10 was mainly detected in cancer cell cytoplasm, and the proportion of MMP-10-expressing cancer cells (median 13.8%) was significantly higher (P<0.001) than non-tumoral gland cells (2.4%). Similarly, the proportion of MMP-10-expressing cancer cells was significantly higher (P=0.007) in stage pT3 (median 22.3%) than in pT2 (11.3%) tumors and was correlated with blood vessel invasion (P=0.025). In addition, its expression level correlated significantly with CRI (r=0.34, P=0.001), but not with PI, AI or MVD. Multivariate analysis identified MMP-10 expression to be closely associated with pT stage (OR 3.76, 95% CI 1.14-12.34, P=0.029). Our results suggest that the overexpression of MMP-10 produces an imbalance in cancer cell proliferation and apoptosis, thereby contributing to cancer cell progression of non-metastatic prostate cancer.

Clinical significance and prognostic value of S100A4 and matrix metalloproteinase-14 in patients with organ-confined bladder cancer.

Various therapeutic modalities are available for treatment of bladder cancer, and their effectiveness and patient outcome often depend on cancer cell invasiveness. However, the mechanisms underlying the early steps of bladder cancer cell invasion remain unknown. This study aimed to clarify the relationships between S100A4 expression and bladder cancer invasion of surrounding muscles, prognosis and expression of matrix metalloproteinase (MMP)-14 in patients with organ-confined bladder cancer. S100A4 and MMP-14 expression was analyzed in 85 cases of organ-confined (pTa, pT1 and pT2) bladder cancer using immunohistochemical technique. The expression levels were compared among the pTa, pT1 and pT2 tumors. In addition, the predictive values of S100A4 or MMP-14 expression for muscle invasion, metastasis and survival were investigated, as was the possible correlation between the expression of the two proteins. The proportion of S100A4-positive cancer cells in pT2 tumors (53%) was significantly higher (p<0.001) than in pTa (38.7%) or pT1 (40.9%) tumors; there was no difference between pTa and pT1. The results were similar for MMP-14 expression, which was significantly correlated with S100A4 expression (r=0.360, p<0.001). S100A4 expression predicted metastasis-free survival (p=0.009), but not cause-specific survival. The results implicated S100A4 in the early steps of muscle invasion via MMP-14, but not for mucosal invasion. S100A4 is therefore a potential therapeutic target for bladder cancer, and its expression is a risk factor for muscle invasion in patients with superficial tumors. In addition, S100A4 expression may be a useful prognostic factor for metastasis in patients with organ-confined bladder cancer.

Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy.

PURPOSE: X-linked inhibitor of apoptosis (XIAP) has high affinity and strong inhibitory activity on apoptosis-related caspase-3. The relationships between expression of XIAP and cleaved caspase-3, and response to neo-adjuvant hormonal therapy (NHT) remain elusive. The aim was to investigate whether NHT influences with XIAP expression in prostate cancer patients. In addition, the relationship between XIAP expression and apoptosis in patients who did or did not receive NHT was also investigated. METHODS: Eighty-three patients who had undergone radical prostatectomy were examined retrospectively and divided into NHT group (n = 40) and non-NHT group (n = 43). Immunohistochemistry was used to analyze the expressions of XIAP and cleaved caspase-3. The apoptotic cells reconfirmed the number of terminal deoxynucleotidyl transferase-mediated nick and labeling (TUNEL)-positive cells. RESULTS: In the non-NHT group, the proportion of TUNEL-positive cells correlated with expression of cleaved caspase-3 (r = 0.592, P < 0.001), and the expression of XIAP correlated negatively with that of cleaved caspase-3 and TUNEL-positive cells (r = -0.464, P < 0.001 and r = 0.431, P = 0.002, respectively). The expression of cleaved caspase-3, but not that of XIAP, was higher in NHT group than non-NHT group (P = 0.017). In the NHT group, there was no significant correlation between XIAP expression and cleaved caspase-3 expression or the proportion of TUNEL-positive cells. CONCLUSIONS: NHT did not influence XIAP expression. We speculate that the inhibition of XIAP expression may reinforce the apoptotic effect of NHT and improve the prognosis in patients with prostate cancer.

Lymphangiogenesis and angiogenesis in conventional renal cell carcinoma: association with vascular endothelial growth factors A to D immunohistochemistry.

OBJECTIVES: Lymphangiogenesis is associated with tumor progression in various cancers and is regulated by vascular endothelial growth factors (VEGFs). However, little is known about the pathologic roles of lymphangiogenesis in renal cell carcinoma (RCC). We investigated the relationships between various clinicopathologic features and lymphangiogenesis, angiogenesis, and expression of VEGFs in RCC. METHODS: The TNM stage and grade of 107 conventional RCC were reviewed. Lymph vessel density (LVD) and microvessel density (MVD) were measured by quantitative immunohistochemistry using anti-D2-40 antibody and anti-CD34 antibody, respectively. Expression levels of VEGF-A, B, C, and D were examined by immunostaining. RESULTS: D2-40-positive lymphatic vessels were detected mainly in the peritumoral area. However, no significant difference was found between LVD in peritumoral areas of the RCC tissues and the normal kidney (P = 0.238). Intratumoral D2-40-positive lymphatic vessels were detected in only six specimens, and neither intratumoral nor peritumoral LVD correlated with the clinicopathologic features. VEGF-A expression correlated with MVD (r = 0.50, P <0.001), but not with LVD, and was also associated with pT stage, the presence of metastasis, and tumor grade. No other members of the VEGF family showed any correlation with LVD, MVD, or the clinicopathologic features. CONCLUSIONS: Lymphangiogenesis seems to play a minimal role in the progression of human RCC. Only VEGF-A, but not B, C, or D, was associated with the histopathologic features and MVD of RCC.

Expression of matrix metalloproteinase-10 in renal cell carcinoma and its prognostic role.

OBJECTIVES: Matrix metalloproteinase (MMP)-10 is associated with malignant aggressiveness in various cancers, but its importance has not been investigated in conventional renal cell carcinoma (CRCC). The purpose of this study was to determine the clinical significance and malignant potential of MMP-10 in human CRCC tissues. PATIENTS AND METHODS: Specimens were obtained from 103 CRCC patients who underwent radical surgery and were examined by immunohistochemistry for MMP-10 expression. The proportions of Ki-67-stained cells (proliferation index: PI) and densities of CD34-positive vessels (microvessel density: MVD) were measured by a computer-aided image analysis system. The relationships between MMP-10 expression and clinicopathologic features and various parameters including tumour size, PI, MVD, and survival were investigated by univariate and multivariate analyses. RESULTS: MMP-10 expression was mainly detected in cancer cell cytoplasm, and 45 (43.7%) CRCCs were considered MMP-10-positive. MMP-10 expression correlated with grade (p=0.006) and pT stage (p<0.001), and it was a significant and independent factor for high pT stage in multivariate analysis model. MMP-10 expression was associated with MVD (p = 0.022) but not tumour size or PI. MMP-10 expression in CRCC was a significant predictor of poor outcome by log-rank test (p = 0.013) but not by multivariate analysis. CONCLUSIONS: MMP-10 seems to play an important role in renal cancer cell invasion and is a potentially useful therapeutic target to prevent CRCC tumour progression.