Preoperative parameters, including percent of positive biopsy cores, in predicting pathological findings after radical prostatectomy

OBJECTIVES: We investigated whether preoperative parameters predict pathological stage at radical prostatectomy for patients with clinically localized prostatic cancer. MATERIALS AND METHODS: We studied a total of 160 men with clinically localized prostatic cancer (less than or equal to clinical T2) who underwent radical rertropubic prostatectomy at Wakayama Medical University. Clinical Ts patients are not included in this study. Preoperative parameters include patient age, Body Mass Index, preoperative serum PSA value, biopsy Gleason score, clinical stage, the percent of positive biopsy cores (%PosBx) and the percent of positive biopsy cores on the dominant side (%DomPosBx). Univariate and multivariate analysis were performed to examine the prognostic significance of these preoperative parameters. Significant independent factors were combined to create a table to predict pathologically organ confined disease. RESULTS: Univariate analysis showed preoperative serum PSA value (p< 0.001), biopsy Gleason score (p =0.001), clinical stage (p = 0.026), %PosBx (p= 0.002) and %DomPosBx (p=0.003) were significantly related to the pathological stage. On multivariate analysis, serum PSA value (p< 0.01), biopsy Gleason score (p<0.05) and %DomPosBx (p<0.05) were significant independent predictors of pathological stage. CONCLUSION: We provide two model combinations using preoperative clinical factors, one is a combination of serum PSA and biopsy Gleason score and the other is a combination of serum PSA and %DomPosBx, which define a new preoperative model for predicting pathological organ confined prostatic cancer. These combinations are useful and provide important information for urologists to determine the appropriate treatment strategy for clinically localized prostatic cancer.     

Comprehensive analysis of gene expression in testes producing haploid germ cells using DNA microarray analysis

The comprehensive changes in testicular gene expression before and after haploid germ cell differentiation were examined using microarray analysis. Approximately 14,000 expressed sequence tag (EST) clones of Mouse FANTOM Array ver.1 were hybridized with probes generated from mRNA of adult and juvenile (17 days postpartum) testes before the onset of spermiogenesis. Of 1315 genes that exhibited reproducible changes in expression (p < 0.05), 46% exhibited an increase of twofold or more in adults compared to juveniles, and 22% a decrease of twofold or more. The analysis not only confirmed the reported haploid-specific expression of several known genes, but also provided new information on the differential expression of various other genes, including upregulated genes such as Allc and Skd3 and downregulated genes such as hbb b1, before or after the onset of spermiogenesis. Based on the fundamental difference in expression profiles, and molecular functions of the encoded products, the genes were classified into several groups: postmeiotically upregulated genes encoding various enzymes, structural and regulatory proteins, and chaperones, and downregulated genes encoding haemoglobins and oxidation/reduction-related proteins or the machinery associated with protein synthesis, such as ribosomal proteins.     

Hepatocyte growth factor and transforming growth factor β1 contribute to regeneration of small-for-size liver graft immediately after transplantation

Although the ability of the liver to regenerate to a predetermined size after resection made adult-to-adult living donor liver transplantation (LDLT) possible, there is little information regarding the growth regulatory mechanism for a small-for-size graft. Forty-one cases of LDLT were divided into two groups by graft volume to standard liver volume ratio (GV/SLV); small graft group (Group S, GV/SLV<40%, n=16) and non-small graft group (Group NS, GV/SLV>40%, n=25). The regeneration rate (GV at 1 week/harvested GV) and serum levels of hepatocyte growth factor (HGF), transforming growth factor- (TGF-) and transforming growth factor-1 (TGF-1) were compared between two groups. The regeneration rates in Group S were significantly higher than that of Group NS (217±12% and 178±10%, respectively, P<0.01). The serum HGF levels of Group S were significantly higher than those of Group NS on POD 1. The TGF-1 levels of Group S were significantly higher than those of Group NS on POD 3 and 5. The TGF- levels were not different at any time points studied. These results indicate that a small-for-size graft retains the capacity to regenerate faster by modulation of expression pattern of HGF and TGF-1 immediately after LDLT. After the acceleration of the regenerative response by HGF, subsequent elevation of TGF-1 synergistically controls graft size, regulating uncontrolled proliferation of hepatocytes.     

Case of autosomal dominant polycystic kidney disease associated with congenital hepatic fibrosis

A 31-year-old man was admitted to the hospital because of a low-grade fever, general malaise, nausea, vomiting, and a poor appetite. On admission his renal function was severely deteriorated (serum creatinine 16.12 mg/dl, BUN 163 mg/dl), and he had severe anemia (Hb 7.5 g/dl) and thrombocytopenia (67,000/microl). A radiological examination revealed the presence of multiple cysts in his kidneys bilaterally. The patient was diagnosed as having end-stage renal disease due to polycystic kidney disease, and hemodialysis was started on the day of admission. After the initiation of hemodialysis, his symptoms and laboratory tests improved, except for anemia and thrombocytopenia. He was noted to have marked splenomegaly and dilation of the portal vein, raising the suspicion of portal hypertension as the cause of the splenomegaly and pancytopenia. To treat his pancytopenia (anemia and thrombocytopenia) and to determine the reason for his portal hypertension, a splenectomy and open-wedge biopsy of the liver were performed. Histological findings in the liver included extensive fibrosis of the portal areas with an excess of moderately dilated bile ducts, compatible with a diagnosis of congenital hepatic fibrosis. After splenectomy, his red blood cell and platelet counts returned to normal, and he was discharged on maintenance dialysis. Congenital hepatic fibrosis is often associated with autosomal recessive polycystic kidney disease (ARPKD), but not with autosomal dominant polycystic kidney disease (ADPKD). However, both his mother and older brother had multiple renal cysts, indicating that this was an unusual case of ADPKD complicated by congenital hepatic fibrosis.     

A case of hepatoblastoma occurring in an adult

We present herein a rare case of hepatoblastoma occurring in an adult male. The patient was 22 years old and his laboratory investigations on admission showed a marked elevation of α-fetoprotein in the serum. CT scan and other examinations revealed a primary tumor, 6.5 cm in size, in the left hepatic lobe with metastasis in the head of the pancreas. Thus, left hepatic lobectomy and pancreaticoduodenectomy were performed, but metastasis to the right hepatic lobe, left lung and abdominal skin were found 2 months later. Despite repeated courses of chemotherapy with adriamycin and cisplatin, the patient died 9 months after his operation. Pathological findings revealed poorly differentiated type hepatoblastoma. A review of the literature revealed only twelve other such cases.     

Mutations of the p53 and ras genes in childhood t(1;19)-acute lymphoblastic leukemia

We have investigated the alterations of p53 and ras genes including H-, K-, and N-ras genes in 22 acute lymphoblastic leukemia (ALL) cases and five cell lines carrying t(1;19) by use of polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis and direct sequencing. The mutations of the p53 gene were found in 2 of 20 t(1;19)-ALL cases at diagnosis (10%), all of 4 cases at relapse (100%), and 4 of the 5 cell lines (80%). Four of the five patients who died had missense mutations at codons 49, 177, 179, and 248. In cases examined sequentially, one had the same point mutation at codon 179 at both diagnosis and relapse, and another had the same p53 gene mutation at codon 240 both in leukemic cells at relapse and in a cell line derived at that time. The other case had no mutation at diagnosis but had the mutation at codon 177 at relapse and cell lines derived from blast cells at diagnosis, suggesting that a small number of leukemic cells with the p53 gene mutation at diagnosis might have escaped PCR-SSCP analysis. In cell lines, SCMC-L9 had three point mutations in the p53 gene at codons 175, 248, and 358, whereas SCMC-L10 had frame shift at codons 209-211. One case had a rare polymorphism at codon 11. We found only one mutation of the N-ras gene that was a 2-bp substitution of GGT(Gly) to GTC(Val) at codon 13 among 22 t(1;19)-ALL cases and five cell lines. This case showed no mutation of the p53 gene and has had a good course. These results suggest that in t(1;19)-ALL, mutations of the p53 and ras genes are infrequent at diagnosis and that p53 gene alterations may be associated with relapse phase or progression of t(1;19)-ALL.