Emphysematous pyelonephritis with complete duplication of the left urinary tract.

Emphysematous pyelonephritis (EPN) is a life-threatening bacterial infection and should be treated rapidly and carefully. We report a case of EPN with complete duplication of the left urinary tract. A 68-year-old woman was admitted to our hospital complaining of high-grade fever and left flank pain. An abdominal computed tomography scan showed gas was presented in the renal parenchyma, not only the pelvis and ureter. Based on these findings, a diagnosis of left EPN was made. A partial nephrectomy of the affected left upper pole moiety was performed and the patient underwent additional medical management. Other 83 cases of EPN from the Japanese literature were reviewed.

Prognosis of Japanese metastatic renal cell carcinoma patients in the cytokine era: a cooperative group report of 1463 patients.

BACKGROUND: Incidence rate of renal cell carcinoma (RCC) differs among countries. The rates of Asian countries are lower than those of countries in North America or Europe but are exceptionally high in Japanese males. Approximately 30% of patients with RCC have metastasis at initial diagnosis, and another 30% have metastasis after nephrectomy. Clinical studies of risk factors in patients with metastatic RCC (mRCC) are mainly based on data from non-Asian patients. OBJECTIVES: We aimed to investigate the prognosis of Japanese patients and their prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: The subjects of this study were 1463 patients who were clinically diagnosed with RCC with metastasis in 40 Japanese hospitals between January 1988 and November 2002. MEASUREMENTS: The primary end point was overall survival calculated from first diagnosis of mRCC to death or last follow-up. We also investigated the relationship between survival and clinical features. RESULTS AND LIMITATIONS: The median overall survival time was 21.4 mo. The estimated survival rates at 1, 3, 5, and 10 yr were 64.2%, 35.2%, 22.5%, and 9.1%, respectively; they contrasted with data from the United States of 54%, 19%, 10%, and 6%, respectively for the same periods. A high percentage of patients had undergone nephrectomy (80.5%) and metastasectomy (20.8%), both of which were shown to prolong survival. CONCLUSIONS: The median survival time in the present study was approximately twice as long as that of previous studies from North America or Europe. Early diagnosis of metastasis, nephrectomy, metastasectomy, and cytokine-based therapy seemed to improve the prognosis of RCC patients in the present study.

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.

[A case of metastatic tumor of spermatic cord from ascending colon carcinoma].

A 75-year-old man presented with a left inguinal mass two months after surgery for ascending colon cancer. Physical examination revealed a solid mass in the left inguinal area. High orchiectomy was performed under the diagnosis of spermatic cord tumor. Gross examination of the specimen revealed a 5.0 X 3.2 X 3.0 cm tumor in the spermatic cord. Pathological examination of the tumor was reported as poorly differentiated adenocarcinoma with features similar to those of previously resected colon cancer. He developed peritonitis carcinomatosa and died 6 months after left orchiectomy. To our knowledge, a metastatic tumor of the spermatic cord from colon or rectal cancer is rare. As previously reported, the prognosis of this case was also poor.

[Progress in therapeutic strategy for renal cell carcinoma].

The standard treatment for renal cell carcinoma (RCC) is surgery. Partial nephrectomy is often performed for treatment of small RCC. Radiofrequency ablation (RFA) offers another nephron-sparing minimally invasive approach. It is most successful for tumors not larger than 3 cm in diameter. The rate of severe complications of RFA is low. Further studies are necessary to determine the long-term efficacy of RFA in RCC. Metastatic RCC is currently mainly treated with cytokine-based therapy. Transient responses and moderate survival advantages have been achieved in a subset of patients. New therapies such as targeted molecular therapies are being developed to improve efficacy and treat those patients who are resistant to systemic immunotherapy. Targeted molecular therapies include inhibition of the Raf kinase pathway, inhibition of its receptor kinases, anti-vascular endothelial growth factor monoclonal antibody or the mammalian target of rapamycin pathway. Further clinical research will be required to develop a more effective therapy and the application of combined treatment modalities.

Interstitial expression of heat-shock protein 47 correlates with capillary deposition of complement split product C4d in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN), associated with late-allograft dysfunction is caused by alloantigen-dependent and -independent mechanisms, and eventually leads to interstitial fibrosis (ci). Activation of complement cascade is considered to be a poor prognostic marker of graft survival. This study was designed to examine the relationship between the expression of C4d and heat-shock protein 47 (HSP47, a collagen-specific chaperone) in the development of interstitial fibroproliferative lesions in CAN. METHODS: Sixty-three renal allograft biopsy specimens, obtained from 48 patients, were examined for the expression of C4d, HSP47, CD68 and alpha-smooth muscle actin (alpha-SMA) by immunohistochemistry. Double-staining was performed to determine the colocalization of C4d and HSP47. The relationship of between the expression of C4d, HSP47, CD68 and alpha-SMA and the clinical and histopathological parameters were statistically analysed. RESULTS: No expression of C4d was noted in the tubulointerstitium including peritubular capillary (PTC) of the control kidney. C4d was expressed in PTC in one-third of allograft renal tissues with morphological evidences of CAN. The interstitial cells around the fibrotic areas of the PTC of CAN were positive for the expression of HSP47. The deposition of C4d in PTC correlated with interstitial expression of HSP47 around the PTC. Most HSP47 expressing cells were phenotypically altered myofibroblasts, as determined by the dual staining of alpha-SMA. CONCLUSIONS: The increased expression of HSP47 positively correlated with the expression of C4d in PTC, and might contribute to the progression of interstitial ci in CAN.

Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitors in patients with renal cell carcinoma: correlation with tumor associated macrophage and prognosis.

PURPOSE: Urokinase-type plasminogen activator (uPA) has an important role in tumor progression through the degradation of extracellular matrix. In addition, uPA receptor (uPAR) and plasminogen activator inhibitors (PAIs), composed of PAI-1 and 2, are also known to affect such activities. Tumor associated macrophage (TAM) is an important regulator of tumor progression that is associated with the uPA system in various cancers. However, to our knowledge the clinical significance of PAI-2 and the relationship between the uPA system and TAM in human renal cell carcinoma (RCC) tissues have not been investigated. We investigated and clarified these issues. MATERIALS AND METHODS: The subjects of the current study were 106 consecutive surgically resected specimens from patients with RCC. The expression of uPA, uPAR, PAI-1 and PAI-2 was determined by immunohistochemistry. We also examined the relationships among these molecules, survival and TAM. RESULTS: The mean immunoreactive scores (range 0 to 6) of uPA, uPAR, PAI-1 and PAI-2 were 3.09, 2.22, 1.99 and 0.56, respectively. These scores correlated with the grade and presence of metastasis. The expression of uPA, uPAR and PAI-1 but not PAI-2 correlated negatively with cause specific survival. Of uPA family members multivariate analysis showed that PAI-1 independently influenced cause specific survival. TAM counts correlated with PAI-1 only (p <0.001). CONCLUSIONS: Our results suggest that PAI-1 is an important regulator of tumor progression and survival, and PAI-1 may modulate them via TAM. On the other hand, PAI-2 has a minimum role in survival. Our results may help discussions of treatment strategy in patients with RCC.

Predictive value of serum macrophage colony-stimulating factor for development of aortic calcification in haemodialysis patients: a 6 year longitudinal study.

BACKGROUND: Accelerated atherosclerosis is a major complication in patients on haemodialysis (HD). Macrophage colony-stimulating factor (MCSF) is a representative regulator of activation of monocytes and macrophages, and plays important roles in the development of atherosclerosis in HD patients. However, the long-term predictive value of the serum MCSF level for the development of aortic calcification under HD conditions has not been reported. METHODS: Serum MCSF level was measured in 40 HD patients. The aortic calcification index (ACI) was also calculated on computed tomography once each year for 6 years. Predictive value was examined by logistic regression analysis. RESULTS: At baseline, there was a significant correlation between serum MCSF and ACI (r = 0.43, P<0.01). A significant increase in ACI was first noted at 4 years post-baseline and the increase was maintained thereafter in the high MCSF group. No such changes were noted in the low MCSF group. Univariate analysis identified high levels of calcium x phosphorus product, triglyceride, C-reactive protein (CRP), MCSF and presence of diabetes mellitus as significant predictors for increased ACI at 6 years. However, among these five factors, high levels of CRP and MCSF were the only independent and significant predictors (odds ratio = 24.0, P = 0.03 and odds ratio = 22.8, P = 0.02, respectively). CONCLUSIONS: Our results demonstrated that MCSF is associated with the process of atherosclerosis in HD patients. Furthermore, the serum MCSF level is an independent long-term predictor of increased ACI. These results provide useful information for preventive strategies against atherosclerotic disease under HD conditions.

Expression of nm23-H1 gene product in sarcomatous cancer cells of renal cell carcinoma: correlation with tumor stage and expression of matrix metalloproteinase-2, matrix metalloproteinase-9, sialyl Lewis X, and c-erbB-2.

OBJECTIVES: To investigate the clinical significance of nm23-H1 gene product in sarcomatous cancer cells, because this is known as a tumor-metastasis suppressor. Renal cell carcinoma with sarcomatoid cancer cells is characterized by high malignant potential and a poor prognosis. METHODS: We investigated the expression of nm23-H1 gene product in the carcinomatous and sarcomatous component (CC and SC) of renal cell carcinoma using immunohistochemical techniques and the relationships between the expression and clinicopathologic features. We also examined the expression of matrix metalloproteinase (MMP)-2, MMP-9, sialyl Lewis X, and c-erbB-2 in the SC because these proteins are regulated by the nm23-H1 gene or its products. RESULTS: We examined 20 renal cell carcinoma specimens that contained an SC and CC. The CC of 12 of the 20 tumors stained positively for nm23-H1 gene product. In contrast, the SC of only 3 of the 20 stained positive. The reduced expression of nm23-H1 gene product in the SC correlated significantly with tumor invasion (P <0.01), but not with tumor size or metastasis. In contrast, the expression of the nm23-H1 gene product in the CC was not associated with these pathologic features. Expression of the nm23-H1 gene product correlated negatively with MMP-2 expression (r = -0.48, P = 0.03). Other factors did not show such significant correlations with nm23-H1 gene product expression. CONCLUSIONS: Our results suggest that low expression of nm23-H1 gene products may play important roles in tumor invasion, and that this process is mediated in part by overexpression of MMP-2.

Mucinous adenocarcinoma of the renal pelvis associated with transitional cell carcinoma in the renal pelvis and the bladder.

We report a case of mucinous adenocarcinoma of the renal pelvis associated with bladder carcinoma in situ (CIS). Transitional cell carcinoma (TCC) of the renal pelvis and CIS were also observed adjacent to the adenocarcinoma. Immunohistochemical assessment of the pelvic adenocarcinoma revealed positive expressions for mucin, epithelial membrane antigen, cytokeratin 7, cytokeratin 19 and carcinoembryonal antigen, but not vimentin or chromogranin. Based on the histopathological examinations, the adenocarcinoma of the renal pelvis in the present case may have a similar biological nature to conventional TCC and probably originated by development of pre-existing TCC of the renal pelvis.

Erectile dysfunction in hemodialysis patients with diabetes mellitus: association with age and hemoglobin A1c levels.

AIM: Erectile dysfunction (ED) is common in patients with diabetes mellitus (DM) as well as those undergoing hemodialysis (HD). The purpose of this study is to investigate the frequency and severity of ED in HD patients with DM and those without DM. In addition, we examined the relationship between erectile function and several risk factors, including presence of DM and hemoglobin A1c levels in HD patients. METHODS: This study involved 180 patients on HD, including 66 HD patients with DM (DM-HD) and 114 patients without DM (non-DM-HD). We evaluated erectile function using an abridged five-item version of the international index of erectile function (IIEF-5). Logistic regression analysis was used to investigate the relationship between presence of ED and several risk factors. RESULTS: The total score of IIEF-5 in DM-HD patients (9.5 +/- 4.2) was significantly lower than in non-DM-HD patients (13.5 +/- 5.7). The prevalence of severe ED was 42.4% and 18.4% in DM-HD patients and non-DM-HD patients, respectively. Age, cardiovascular disease history, and DM were identified as independent risk factors for the presence of ED. Furthermore, age and elevated hemoglobin A1c levels were identified as independent risk factors for the presence of severe ED. CONCLUSION: DM-HD patients are more likely to have ED, and particularly severe forms of ED, than non-DM-HD patients. DM and elevated hemoglobin A1c levels were associated with the presence of ED or severe ED, respectively. Aging was identified as an independent factor in both ED and severe ED.

Spontaneous peripelvic extravasation of urine due to an inflammatory aneurysm of the abdominal aorta.

A 71-year-old man presented complaining of severe left flank pain. A computed tomography scan of the abdomen disclosed a left peripelvic extravasation of urine and a 4.0-cm abdominal aortic aneurysm with a significant amount of perianeurysmal thickening and prominent left hydroureter. The patient was diagnosed as having an inflammatory aneurysm of the abdominal aorta (IAAA) with peripelvic extravasations of urine. We report the results of a patient with IAAA with ureteral obstruction successfully treated with steroid therapy and a ureteral stent.

Primary malignant lymphoma of the female urethra.

BACKGROUND: Malignant lymphoma rarely affects the genitourinary tract. We present a case of malignant lymphoma of the female urethra and review the associated literature to evaluate the management and prognosis. MATERIALS AND RESULTS: A 69-year-old woman presented with a 3-month history of dysuria and a red mass at the external urethra without lymphadenopathy. Pathological examination revealed malignant lymphoma. She was treated with excision of the mass and chemotherapy. Six months later she showed no urethral or other recurrence. An additional 17 cases similar to this one were found in the literature. The one-year survival rate was 91% for local stage and less than 35% for disseminated stage. A significant difference was observed between survival rates (log rank test; p = 0.013). CONCLUSION: It appears that therapy including excision, radiation and chemotherapy is effective for patients with local stage but not for patients with disseminated stage.

EPO-producing gastric carcinoma in a hemodialysis patient.

A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy. Serum erythropoietin level was 181 mU/mL (181 IU/L). Gastroscopy results showed rough mucosa with hemorrhaging caused by gastric cancer. The patient underwent distal gastrectomy, and serum erythropoietin level decreased to 27.1 mU/mL (27.1 IU/L) by postoperative day 8. Existence of erythropoietin in the tumor tissue was confirmed immunohistochemically. The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis.

Expression of thrombospondin-derived 4N1K peptide-containing proteins in renal cell carcinoma tissues is associated with a decrease in tumor growth and angiogenesis.

PURPOSE: We have reported that the 4N1K peptide (KRFYVVMWKK) from thrombospondin (TSP) 1 has antiangiogenic activities. The goal of this study was to examine whether the expression of 4N1K-containing proteins correlates with reduced growth of human renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: We examined the expression of 4N1K-containing proteins and TSP1, microvessel density, proliferation index, and apoptotic index in 119 surgically excised RCC tissues by immunohistochemical techniques. The correlation between the above variables and clinicopathological features was analyzed statistically. RESULTS: The antibody raised against the 4N1K peptide recognized protein fragments of matrix metalloproteinase 3-digested TSP1 and positively stained the sections of renal cancer tissues. These reactions disappeared when the antibody was preincubated with immobilized 4N1K peptide, suggesting that the reactions were 4N1K peptide specific. Although TSP1 expression did not correlate with various clinicopathological features and tumor size, all 4N1K-positive tumors were locally confined and of significantly smaller size (median, 3.3 cm; range, 2.0-4.4 cm) than 4N1K-negative tumors (median, 5.2 cm; range, 2.8-8.8 cm; P < 0.001). 4N1K-positive tumors exhibited significantly lower microvessel density and higher apoptotic index of tumor cells than 4N1K-negative tumors (P < 0.001 and P = 0.042, respectively). CONCLUSIONS: Our data suggest that expression of 4N1K-containing proteins in tumor tissues is associated with reduced angiogenesis and tumor growth; thus, it would be a potentially predictive marker for progression of RCC.

Expression of cyclooxygenase-2 in renal cell carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, expression of matrix metalloproteinase-2, and survival.

PURPOSE: Cyclooxygenase (COX)-2 plays an important role in tumor cell proliferation, resistance to apoptosis, angiogenesis, and invasion in various malignant tumors. However, the relationships between COX-2 expression and these biological processes, clinicopathological features, and survival rate in patients with renal cell carcinoma are not clear. EXPERIMENTAL DESIGN: Tumor sections surgically removed from 131 patients were examined for COX-2 expression by immunohistochemistry. We also examined Ki-67 labeling index, apoptotic index, microvessel density, and matrix metalloproteinase (MMP)-2 expression, and correlated COX-2 expression with various clinicopathological features and survival. RESULTS: Of 131 sections, 70 (53.4%) were positive for COX-2 expression. COX-2 expression was associated significantly with various clinicopathological features, and correlated with the Ki-67 labeling index, microvessel density, and MMP-2 expression (P < 0.01), but not with the apoptotic index (P = 0.054). COX-2 expression was also identified as an independent risk factor for large tumor size (>7 cm) in multivariate logistic regression model. COX proportional hazards analysis showed that distant metastasis and high T stage were independent prognostic factors [odds ratio (OR), 9.41; 95% confidence interval (CI), 2.16-41.11; P < 0.01 and OR, 5.19; 95% CI, 1.02-26.54; P = 0.048, respectively), whereas COX-2 expression was not (OR, 1.46; 95% CI, 0.24-9.00; P = 0.68). CONCLUSION: COX-2 expression in patients with renal cell carcinoma is associated with several clinicopathological factors, and appeared to play an important role in tumor cell proliferation and MMP-2 expression, but is not a significant prognostic factor.

[Clinical study of sarcomatoid renal cell carcinoma].

Patients with sarcomatoid renal cell carcinoma are rare and have poor survival. We evaluated 14 patients who had renal cell carcinoma with a sarcomatoid component between 1982 and 2000. There were 9 men and 5 women with a median age of 59.5 years (range 32 to 77). Seven patients had a tumor on the right side and 7 on the left side. Thirteen patients had some symptoms and 11 had metastases at the initial visit. Most of them were stage T4 and high nuclear grade cancer and showed elevated acute phase reactants. There were 7 patients followed by interferon therapy, and the cause-specific 5-year survival rate was less than 10%. We confirmed that renal cell carcinoma with a sarcomatoid component often showed local invasion, distant metastasis and poor prognosis.

Overexpression of hepatocyte growth factor receptor in renal carcinoma cells indirectly stimulates tumor growth in vivo.

We examined the role of increased expression of HGFR kinase in in vivo growth of renal carcinoma. Human renal carcinoma cell line, ACHN cells, was transfected with plasmid encoding wild-type HGFR gene to generate cell lines with increased HGFR protein. ACHN cells with elevated HGFR expression, denoted clones 8 and 10, respectively, showed higher basal kinase activities of HGFR and PI3-kinase than those of empty-vector (mock)-transfected cells. Clone 8 and 10 cells grew similar to mock cells in culture. In mice, tumors of these clones grew more rapidly than those of mock cells. Microvessel density of clone 8 or 10 tumors was higher than that of mock tumors. Clone 8 and 10 cells secreted vascular endothelial growth factor-A (VEGF-A) more than mock cells and the secretion was PI3-kinase inhibitor, LY294002-sensitive. Anti-VEGF-A neutralizing antibody significantly inhibited tumor growth of clones 8 and 10 in mice. These results indicate for the first time that overexpression of HGFR tyrosine kinase in renal carcinoma cells participates in rapid tumor growth in vivo.

Spontaneous rupture of an aneurysmal intrarenal arteriovenous fistula.

We present a 65-year-old woman who was found to have a spontaneous rupture of an aneurysmal intrarenal arteriovenous fistula. To our knowledge, the present case is only the 3rd reported in the literature. The preferred method of treatment of ruptures of arteriovenous fistulae is embolization. However, the process of choosing among embolization, surgery, or a combination of both procedures must be individualized for each patient based on vital signs and symptoms.

Severe arteriolar lesion mimicking drug-induced arteriolopathy in a long-term surviving renal allograft.

We report severe arteriolar lesion mimicking drug-induced arteriolopathy in a renal allograft of a 37-year-old Japanese male, who has been treated by conventional immunosuppressive therapy but not administered cyclosporin or tacrolimus for 16 years after renal transplantation. Renal biopsy also showed glomerular changes including transplant glomerulopathy and features of chronic vascular rejection. The cause of the arteriolar lesion remains uncertain. Although its pathogenesis may be multi-factorial, long-term usage of conventional immunosuppressive agents and/or vascular rejection may contribute to the occurrence of the arteriolar lesion. We propose that biopsy study is needed for further understanding of histopathological behaviours of renal grafts in long-term survivors.