Shigehiko Koga

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.

An evaluation of Bosniak's radiological classification of cystic renal masses.

Objective To determine the clinical usefulness of Bosniaks classification of cystic renal masses, the differentiation of which remains difficult despite significant advances in diagnostic imaging.

Systemic immune response after intravesical instillation of bacille Calmette–Guérin (BCG) for superficial bladder cancer

The mechanism of anti‐tumour activity by BCG is not known clearly. However, many studies suggest that immunological response is related to effectiveness of intravesical instillation of BCG in the therapy for superficial bladder carcinoma. Peripheral blood mononuclear cells (PBMC), urine and serum were obtained from patients with superficial carcinoma at various times during the course of BCG instillation. Urine of patients showed increased levels of IL‐1β, IL‐2, IL‐6, tumour necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ) and macrophage colony‐stimulating factor (M‐CSF) after BCG instillation. Levels of IL‐2 and IFN‐γ in the serum also increased after BCG instillation, but IL‐1β, IL‐6, TNF‐α and M‐CSF were not detectable. Maximal levels of IL‐2 and IFN‐γ in the urine or serum were shown after the fourth instillation. BCG‐induced killer cell activity in PBMC increased significantly after the third BCG instillation. These results suggest that BCG instillation involved not only local immunological efforts but also systemic immune responses. Tumour‐free patients produced higher BCG‐induced killer cell activity than tumour recurrence patients. BCG‐induced killer cell activity may be useful for monitoring the effectiveness of intravesical BCG instillation.

Outcome of surgery in cystic renal cell carcinoma.

OBJECTIVES To review cases of cystic renal cell carcinoma treated surgically at our institution and define their clinical and histopathologic features. METHODS Between 1986 and 1998, 21 patients with cystic renal cell carcinoma were treated surgically. Cystic renal cell carcinoma was categorized using Hartmans classification. RESULTS Histopathologic examination demonstrated cystic necrosis in 11 patients, multilocular cystic renal cell carcinoma in 9, and unilocular cystic renal cell carcinoma in 1 patient. Tumors were incidentally found during an evaluation of unrelated disease or a general health checkup in 14 patients (67%). The mean tumor size was 5.6 cm (range 0.5 to 12) for cystic necrosis and 5.4 cm (range 2 to 9) for multilocular cystic renal cell carcinoma. All 9 cases of multilocular cystic renal cell carcinoma were of the clear cell type and tumor grade 1. The mean follow-up period was 65 months (range 9 to 141). The 5-year disease-specific survival rates for multilocular cystic renal cell carcinoma and cystic necrosis were 100% and 80%, respectively. CONCLUSIONS The prognosis for patients with cystic renal cell carcinoma is better than that for patients with solid tumors. In particular, the prognosis of multilocular cystic renal cell carcinoma is excellent. Multilocular cystic renal cell carcinoma represents a distinct subtype of renal cell carcinoma that can be completely cured by surgery.

The diagnostic value of bone scan in patients with renal cell carcinoma.

PURPOSE Bone scan is performed as part of the evaluation of bone metastasis. We assessed the diagnostic value of bone scan in patients with renal cell carcinoma. MATERIALS AND METHODS Bone scan was performed at presentation in 205 patients with confirmed renal cell carcinoma. Abnormal hot areas were further evaluated by x-ray, computerized tomography or surgery. RESULTS Of the 56 patients (27%) with an abnormal bone scan 32 (57%) had osseous metastatic lesions. Overall bone metastasis was present in 34 of the 205 patients (17%). Bone scan had 94% sensitivity and 86% specificity. Of the 124 patients with clinically localized, stages T1-2N0M0 disease exclusive of bone metastasis 6 (5%) had bone metastasis only, whereas 28 of 81 (35%) with locally advanced or metastatic disease had bone metastasis, including 12 (35%) who complained of bone pain and 19 (56%) who presented with other symptoms due to local tumor growth or metastasis at other sites. Three patients (9%) were asymptomatic. There was osseous metastasis without other metastasis, enlarged regional lymph nodes or bone pain in 7 patients, including 1 with stage T1b (2% of all with that stage), 2 with stage T2 (5%), 1 with stage T3a (4%), 1 with stage T3b (6%), 1 with stage T3c (14%) and 1 with stage T4 (6%) disease. CONCLUSIONS Bone scan may be omitted in patients with stages T1-3aN0M0 tumors and no bone pain because of the low proportion of missed cases with bone metastasis.

Gene expression and immunohistochemical localization of basic fibroblast growth factor in renal cell carcinoma

Renal cell carcinoma is known as a neoplastic condition of renal tubular cells and usually shows a hypervascular tumor in angiographic examination. We examined the presence of basic fibroblast growth factor (bFGF) in human renal cell carcinoma. To determine if alterations in bFGF gene expression are present in human renal cell carcinoma, paired samples of normal and neoplastic renal tissue from 6 patients were analyzed for bFGF mRNA content by Northern blot hybridization. In 4 out of 6 patients, tumor tissue expressed bFGF mRNA 2 to 4 times greater than corresponding normal tissue. Two patients showed minimal elevation of tumor bFGF mRNA. The localization of bFGF in the renal cell carcinoma tissue was also examined using immunohistochemical staining, and it was found that bFGF was positively stained at the nuclei of tumor cells and the cell surface. These results suggest that increased expression of bFGF may be associated with neoplastic growth in renal tubular epithelial cells and neovascularization.

Predictive values of acute phase reactants, basic fetoprotein, and immunosuppressive acidic protein for staging and survival in renal cell carcinoma.

OBJECTIVES To determine the clinical significance and predictive value of three acute phase reactants (erythrocyte sedimentation rate, C-reactive protein, and ferritin), as well as basic fetoprotein (BFP) and immunosuppressive acidic protein, in patients with renal cell carcinoma. METHODS Erythrocyte sedimentation rate, C-reactive protein, ferritin, BFP, and immunosuppressive acidic protein levels were measured in 92 patients with renal cell carcinoma diagnosed in 1989 to 1999. The levels were compared with the clinical stage and nuclear grade, and their predictive values of survival were evaluated statistically. RESULTS All markers, with the exception of BFP, correlated with each other and with the clinical stage and nuclear grade. BFP did not correlate with the acute phase reactants. The log-rank test revealed that the levels of C-reactive protein, immunosuppressive acidic protein, and ferritin significantly influenced survival. Multivariate stepwise analysis identified ferritin as the only independent and significant prognostic marker (hazard ratio = 5.624, P = 0.001). However, when age, sex, clinical stage, and nuclear grade were entered into the same analysis, only clinical stage was an independent marker of prognosis. CONCLUSIONS The results of our study demonstrated that serum ferritin is the most useful marker among five tested factors for staging and predicting survival, although the clinical stage is the best parameter that predicts the prognosis of patients with renal cell carcinoma accurately.

Primary renal angiosarcoma: A case report and review of the literature

Primary renal angiosarcoma is very rare. To our knowledge, only 15 cases have been reported to date. A 77‐year‐old Japanese man with a unilateral kidney presented with massive hematuria followed by renal failure. A renal tumor was suspected and a left nephrectomy was performed. The histopathological diagnosis was angiosarcoma of the kidney. A hemorrhagic tumor measuring 10 × 5 cm and clotted blood was found in the modularly area. The atypical tumor cells had a sinusoidal and solid appearance, and showed Immunohistochemically positive reactions for some of the endothelial markers. The patient died about 21 months after the nephrectomy and the autopsy revealed massive metastases to the liver and retroperitoneum. One of the differential diagnoses of the case was anglomyolipoma, because the tumor cells were relatively bland in their histological appearance with entrapped fat cells in the pelvic area. Fifteen case reports with titles that included the term ‘hemangiosarcoma/anglosarcoma’, ‘hemangioendothelloma/endothelloma’ or ‘vascular sarcoma’ of the kidney were reviewed and compared to the present case.

Spontaneous peripelvic extravasation of urine

Spontaneous peripelvic extravasation of urine is relatively uncommon. We experienced 11 cases of spontaneous peripelvic extravasation. Urinary obstruction was caused by calculi in 9 cases, invasion by sigmoid carcinoma in 1 case and ureteral tumour (transitional cell carcinoma) in 1. Six patients presented with signs of peritonitis and 4 out of 9 with calculus did not develop microhaematuria.It is important to differentiate peripelvic extravasation from other acute abdominal conditions. We must pay special attention to patients with signs of peritonitis and normal urinalysis.

Acute Hemorrhagic Cystitis Caused by Adenovirus Following Renal Transplantation: Review of the Literature

We report on 4 male patients with acute hemorrhagic cystitis caused by adenovirus following renal transplantation. These patients showed symptoms of gross hematuria, urinary frequency, burning urination and fever. Adenovirus was isolated in all patients and 3 were positive for serotype 11. Complement-fixing antibody was positive for adenovirus in all cases. Acute hemorrhagic cystitis caused by adenovirus was self-limiting and reduction of immunosuppression was not required for its resolution. Clinical presentation of these patients is described and the literature is reviewed.