Mass Screening for Neuroblastoma and Estimation of Costs

ABSTRACT. On the basis of epidemiological data and medical costs for patients with neuroblastoma, we have calculated the cost of mass screening for neuroblastoma with high performance liquid chromatography (HPLC) compared to the cost when it is not performed. If the sensitivity of the mass screening is 80 % and 22 000 infants are screened annually the cost will be 27809000 yen ($191800). If mass screening is not performed, the cost will be 28 446 000 yen ($196 200). The difference in cost (637 000 yen or $4 400) is fairly small. If the sensitivity is 75 % and 16 500 infants are screened, the difference is also small (174000 yen or $1 200). Therefore, mass screening with the HPLC method will not be an undue financial burden. But re-screening at an older age will be done with less financially favorable results, considering that the sensitivity may not be as high as that of the first screening and that mothers are somewhat reluctant about re-screening. The balance of the cost of mass screening by qualitative methods may also be less favorable, since the detection rate is low.     

Successful treatment for squamous cell carcinoma of the female urethra with combined radio- and chemotherapy

We report on two cases of women with locally advanced squamous cell carcinoma of the urethra. Patient 1 also displayed regional lymph node metastasis. Treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5-fluorouracil and cisplatin. Complete response was obtained in both patients, including the inguinal lymph nodes of Patient 1. Patient 1 experienced recurrent inguinal lymph node metastasis on the contralateral side at 42 months after initial treatment, and the same treatment was performed followed by surgical excision. Both patients remain alive with no evidence of disease, at 12 months after recurrence in Patient 1, and at 27 months after treatment in Patient 2.     

Clinical outcome of retroperitoneal lymph node dissection after induction chemotherapy for metastatic non-seminomatous germ cell tumors

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) following induction chemotherapy has been considered a critical component in the comprehensive management of advanced non-seminomatous germ cell tumors (NSGCT). The objectives of the present study were to review the clinical outcome of patients who underwent RPLND and to evaluate the probability of necrosis alone, based on some readily available clinical data for these patients. METHODS: Forty-seven consecutive patients with NSGCT were treated with first-line chemotherapy at our institution between January 1993 and September 2002. Twenty-four of these patients, who underwent RPLND with normal values of tumor markers after induction chemotherapy, were included in the study. The cause-specific survival rate was calculated using the Kaplan-Meier method. Various predictive factors for the histology were analyzed using multivariate analysis. RESULTS: The pathological findings at resection were necrosis alone in 62.5% of cases, teratoma in 25.0%, and viable cancer in 12.5%. The cause-specific 3-year survival rate of patients who underwent complete and incomplete resection was 100% and 50.0%, respectively. Among several clinical factors, prechemotherapy tumor size less than 50 mm was found to be an independent predictor of necrosis alone (hazard ratio = 4.45, P= 0.04). CONCLUSION: Metastatic tumor size before chemotherapy appears to be one of the most important factors for the prediction of necrosis alone in the resected specimens of RPLND. The prognosis of patients might be influenced by the degree to which resection has been completed.     

Exogenous activated protein C inhibits the progression of diabetic nephropathy

Summary. Background: Activated protein C (APC) can regulate immune and inflammatory responses and apoptosis. Protein C transgenic mice develop less diabetic nephropathy but whether exogenous administration of APC suppresses established diabetic nephropathy is unknown. Objectives: We investigated the therapeutic potential of APC in mice with streptozotocin‐induced diabetic nephropathy. Methods: Diabetes was induced in unilaterally nephrectomized C57/Bl6 mice using intraperitoneal (i.p.) injection of streptozotocin. Four weeks later, the mice were treated with i.p. exogenous APC every other day for 1 month. Results: APC‐treated mice had a significantly improved blood nitrogen urea‐to‐creatinine ratio, urine total protein to creatinine ratio and proteinuria, and had significantly less renal fibrosis as measured by the levels of collagen and hydroxyproline. The renal tissue concentration of monocyte chemoattractant protein‐1 (MCP‐1), vascular endothelial growth factor (VEGF) and the RNA expression of platelet‐derived growth factor (PDGF), transforming growth factor‐β1 and connective tissue growth factor (CTGF) were significantly lower in APC‐treated mice than in untreated animals. The percentage of apoptotic cells was reduced and the expression of podocin, nephrin and WT‐1 in the glomeruli was significantly improved in mice treated with APC compared with untreated mice. The levels of coagulation markers were not affected by APC treatment. Conclusion: Exogenous APC improves renal function and mitigates pathological changes in mice with diabetic nephropathy by suppressing the expression of fibrogenic cytokines, growth factors and apoptosis, suggesting its potential usefulness for the therapy of this disease.     

Is a limited lymphadenectomy targeting obturator nodes alone an adequate procedure for Japanese men undergoing radical prostatectomy?

BACKGROUND: The objective of the present study was to investigate the significance of pelvic lymphadenectomy during radical prostatectomy in Japanese men with prostate cancer. METHODS: A total of 178 consecutive patients who underwent radical prostatectomy and standard pelvic lymphadenectomy targeting the external iliac nodes and obturator fossa for clinically localized prostate cancer were studied. The median observation period of this series was 18 months (range: 3-36 months). RESULTS: Lymph node metastases were detected in 13 patients; that is, positive nodes were located in the external iliac nodes alone in seven patients, the obturator fossa alone in four patients, and both external iliac nodes and obturator fossa in two patients. Of these 13 patients, all of the seven with more than one positive node demonstrated biochemical recurrence, whereas five of the six with single node involvement remained without signs of biochemical recurrence. Furthermore, a single positive node was located in the external iliac region in five of the six patients. When a group at high-risk for lymph node metastasis was defined as those meeting more than two of the following three criteria: (i) pretreatment serum prostate specific antigen value > or = 20 ng/mL; (ii) biopsy Gleason sum > or = 8; or (iii) percentage of positive biopsy core > or = 50%, the incidence of lymph node metastasis was 24.5% in the high-risk group and 0.8% in the low-risk group. CONCLUSIONS: These findings suggest that limited dissection of the obturator node alone may not be sufficient for Japanese men undergoing radical prostatectomy; therefore, we recommend performing standard pelvic lymphadenectomy targeting both the external iliac nodes and the obturator fossa for patients at high-risk of lymph node involvement.     

Microscopic venous invasion in renal cell carcinoma as a predictor of recurrence after radical surgery

BACKGROUND: The objective of the present study was to investigate the significance of microscopic venous invasion (MVI) as a prognostic factor for patients with renal cell carcinoma (RCC) who underwent radical surgery. METHODS: The study included a total of 157 consecutive patients with non-metastatic RCC who underwent radical surgery between January 1986 and December 2002. The median follow-up period was 45 months (range 6-162 months). Microscopic venous invasion was defined by the presence of a cancer cell in blood vessels based on the examination of hematoxylin-eosin stained specimens. Other prognostic variables were assessed by multivariate analysis to determine whether there was a significant impact on cancer-specific and recurrence-free survivals. RESULTS: Microscopic venous invasion was found in 70 patients, and of this number, 17 (24.7%) developed a tumor recurrence and 12 (17.1%) died of cancer progression, while only six (6.9%) of the remaining 87 patients without MVI presented with disease-recurrence and three (3.5%) died of cancer. Among the factors examined, the presence of MVI was significantly associated with age, mode of detection, tumor size, pathological stage and tumor grade; however, only pathological stage was an independent predictor for disease-recurrence, and none of these factors were available to predict cancer-specific survival in multivariate analyses. In 120 patients with pT1 or pT2 disease, MVI was noted in 36 patients. In this subgroup, recurrence-free survival rates in patients with MVI were significantly lower than those in patients without MVI, and MVI was the only independent prognostic predictor for disease-recurrence in a multivariate analysis. CONCLUSION: Microscopic venous invasion is not an independent prognostic factor in patients with non-metastatic RCC who underwent radical surgery; however, it could be the only independent predictor of disease-recurrence after radical surgery for patients with pT1 or pT2 disease.     

Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model

BACKGROUND: The objectives of this study were to evaluate the antitumor effects of the simultaneous introduction of interleukin 12 (IL-12) and IL-18 genes into a mouse bladder cancer cell line (MBT2). We intended to compare these with those of either gene alone and to investigate the mechanism of the effects induced by the transfer of IL-12 and/or IL-18 genes in this model system. METHODS: We transfected the IL-12 and/or IL-18 genes into MBT2 cells by the liposome-mediated gene transfer method. We confirmed the secretion of IL-12 and/or IL-18 by enzyme-linked immunosorbent assay. Parental (MBT2/P), IL-12-transfected (MBT2/IL-12), IL-18-transfected (MBT2/IL-18) or both IL-12- and IL-18-transfected (MBT2/Both) cells were subcutaneously or intravenously injected into syngeneic C3H mice. To analyze the mechanism of tumor rejection, these clones were subcutaneously injected into naive nude mice and those depleted with natural killer (NK) cells by antibody. RESULTS: MBT2/IL-12, MBT2/IL-18 and MBT2/Both were completely rejected when they were injected subcutaneously or intravenously into syngeneic mice. However, MBT2/IL-12, but not MBT2/IL-18, could grow in nude mice. Moreover, the antitumor effect of MBT2/IL-18 was partially abrogated when injected into nude mice of which NK cells were depleted by antibody treatment. MBT2/Both was completely rejected in both nude mice with and without NK cells. CONCLUSION: The results of the present study indicate that T cells and NK cells seem to play important roles in the antitumor effects by the secretion of IL-12 and IL-18, respectively, and MBT2/Both possesses both mechanisms.     

Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy

BACKGROUND: We analyzed the outcome of repeated transrectal ultrasound (TRUS)-guided systematic prostate biopsy in Japanese men whose clinical findings were suspected of prostate cancer after previous negative biopsies. METHODS: Between January 1993 and March 2002, 1045 patients underwent TRUS-guided prostate biopsy. Among them, 104 patients underwent repeat biopsy due to indications of persistent elevated serum prostate-specific antigen (PSA), abnormal digital rectal examination (DRE) or TRUS, increased PSA velocity, and/or previous suspicious biopsy findings. Several clinicopathological factors were evaluated for their ability to predict the detection of prostate cancer on repeat biopsy. RESULTS: Prostate cancer was detected in 22 of 104 patients (21.2%) who underwent repeat biopsies. PSA concentration and PSA density at both the initial and repeat biopsies, and PSA velocity in men with positive repeat biopsy were significantly greater than those in men with negative repeat biopsy. The incidence of abnormal findings in DRE and TRUS at initial biopsy in men with positive repeat biopsy was also significantly higher than that in men with negative repeat biopsy. However, neither the presence of prostatic intraepithelial neoplasia nor number of biopsy cores at initial biopsy had a significant association with the results of the repeat biopsy. Furthermore, multivariate analysis revealed that PSA and PSA density at both the initial and repeat biopsies, PSA velocity, and DRE and TRUS findings at initial biopsy were independent predictors of malignant disease on repeat biopsy. CONCLUSION: Despite an initial negative biopsy, repeat TRUS-guided biopsy should be carried out to exclude prostate cancer in cases of suspicious clinical findings, such as elevated PSA or PSA-related parameters, or abnormal findings of DRE or TRUS.