Pathological effects of neoadjuvant hormonal therapy help predict progression of prostate cancer after radical prostatectomy

BACKGROUND: It is not clear whether pathological changes following neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy have any value as predictors of progression in prostate cancer. METHODS: We conducted a study of 100 patients with prostate cancer who underwent radical prostatectomy following NHT. We used the Japanese general rule as the criterion to assess the biochemical recurrence rate and pathological changes after NHT. RESULTS: In terms of preoperative risk factors, the probability of recurrence was significantly higher for patients with more than 20 ng/mL of pretreatment serum prostate-specific antigen (PSA) and/or a Gleason score of 7 or higher for biopsy specimens. We defined these pretreatment findings as high-risk factors. Among 65 patients with high-risk factors, patients with a post-NHT pathological effect of grade 3 according to the Japanese general rule showed no recurrence, whereas patients with a grade 0 had a poor prognosis. Patients with a PSA nadir 0.5 ng/mL or less tended to have a better prognosis. CONCLUSION: Despite preoperative high-risk factors, patients showing good pathological effects after NHT tend to have a favorable prognosis after radical prostatectomy. Therefore; assessment of the pathological effects of NHT using the Japanese general rule as the criterion proved to be useful for the prediction of biochemical recurrence.     

Protective effect of OK-432 (streptococcal preparation) on murine fulminant hepatitis following mouse hepatitis virus infection

The effects of OK-432 (streptococcal preparation) on murine fulminant hepatitis were investigated. Hepatitis was induced by injection of mouse hepatitis virus type 2 (MHV-2) at a strength of either 1 x 10(3) or 1 x 10(4) plaque-forming units (PFU). Mice without OK-432 treatment died within 5 days, whereas mice preinoculated with OK-432 showed survival rates of 50% (1 x 10(3) PFU) or 10% (1 x 10(4) PFU) after 60 days. Survival time was not prolonged if OK-432 was injected after MHV-2. Examined histologically, mice not treated with OK-432 showed severe haemorrhagic necrosis of the liver, often panlobular. Treated mice showed less necrosis; the least necrosis was observed in those injected with OK-432 before MHV-3. In those mice injected first with OK-432 and then with 1 x 10(3) PFU of MHV-2 that survived 7 days, autopsy showed a very slight and focal hepatic necrosis, with follicular infiltration by lymphocytes and macrophages. Mitogenic reaction of spleen cells was remarkably less than normal in mice with MHV-2 injection. However, mice injected with OK-432 before MHV-2 (same treatment as mice showing high survival rates) showed relatively high reactivity in comparison with mice not treated with OK-432.     

Controlled Study of Therapeutic Granulocyte Transfusions in Granulocytopenic Patients with Severe Infections

The effectiveness of therapeutic granulocyte transfusions wasstudied in a controlled trial involving 75 granulocytopenicpatients with severe infections. Patients who had granulocytecounts of less than 200/mm³ and no response to antibiotic therapywere assigned to receive antibiotic therapy alone or granulocytetransfusions plus antibiotic therapy. Granulocytes were collectedby filtration leukapheresis (FL), intermittent flow centrifugeleukapheresis (IFCL) or continuous flow centrifuge leukapheresis(CFCL). Therapeutic effects of granulocyte transfusions wereevaluated on the basis of 20-day survival after entry into thestudy. The patients were divided into three groups: 1) 22 patientsreceived antibiotic therapy alone for 29 infectious episodes(control group); 2) 27 patients received 131 transfusions ofgranulocytes collected by FL for 31 infectious episodes (FLgroup); 3) 26 patients received 139 transfusions of granulocytescollected by IFCL and CFCL for 27 infectious episodes (IFCL& CFCL group). The overall survival of the transfused patientswas not significantly different from that of the untransfusedpatients. Similarly, there was no significant difference insurvival between the transfused and untransfused patients whenthe data concerning septicemia were analyzed. When patientsshowed bone-marrow recovery, which was indicated by recoveryof granulocytes to 500/mm³ or more during the study, 20-daysurvival was observed in 13 of 14 untransfused patients andin all of 26 transfused patients. In contrast, the survivalrate for the patients without bone-marrow recovery was 13% (2/15)in the control group, 39% (7/18) in the FL group and 57% (8/14)in the IFCL & CFCL group respectively. Thus, the survivalrate was significantly higher for the transfused than for theuntransfused patients. These observations suggest that therapeutic granulocyte transfusionsmay be of limited value in improving the outcome of severe infectionsin persistently granulocytopenic patients. Since bone-marrowrecovery is a critical factor for the prognosis of severe infections,therapeutic granulocyte transfusions do not provide any beneficialeffects in granulocytopenic patients whose bone-marrow functionwill recover.     

Viral hepatitis in Japan: Update

Viral hepatitis is defined as a hepatitis virus infection in which hepatic inflammation and necrosis lead to a characteristic feature. It is caused by at least five viral agents with specific epidemio-logical attributes and distinctive immunoserologic findings. The well-characterized forms are hepatitis A, B, C, D and E viruses. Recent status and the current progress of viral hepatitis in Japan are discussed in the present article.     

Comparison of two in vivo models for prostate cancer: Orthotopic and intratesticular inoculation of LNCaP or PC-3 cells

BACKGROUND: The critical events in the clinical course of prostate cancer are the occurrence of metastasis and the induction of the hormone-refractory status of the disease. In order to investigate the factors responsible for these events, we need appropriate in vivo models. MATERIALS AND METHODS: Orthotopic and intratesticular models were created by the injection of LNCaP cells or PC-3 cells into the prostate or testis of severe combined immunodeficient mice. RESULTS: LNCaP cells in the intratesticular model showed a higher incidence of tumor formation and lymph node metastasis when compared with those in the orthotopic model, while PC-3 cells were highly tumorigenic and metastastic in both models. A high concentration of androgens might play a role in tumor aggressiveness of LNCaP cells, given that enhanced mRNA expressions of integrin alphaV and vascular endothelial growth factor was induced by dehydrotestosterone administration in vitro. The high expression of metastasis-related genes, including the urokinase plasminogen activator system, metalloproteinases and vascular endothelial growth factor-C, might be attributed to the high metastatic potential in both models. Interestingly, testicular xenografts of LNCaP cells were able to survive on the subcutis back of castrated male mice as well female mice. CONCLUSIONS: Intratesticular models of prostate cancer appear to be suitable for studying the mechanisms of metastasis and for evaluating various treatment strategies.     

Recurrence pattern for superficial bladder cancer

AIM: Patients with superficial bladder tumors sometimes have long recurrence-free intervals. We evaluated whether patients with long recurrence-free periods had subsequent recurrences. We also clarified how these patients should be followed. MATERIALS AND METHODS: We enrolled 244 patients with superficial bladder cancer (62 pTa and 182 pT1) treated by transurethral resection of bladder tumor (TURBT) and adjuvant chemotherapy with pirarubicin. Median follow up was 75.5 months. Patients were stratified by the length of their recurrence-free interval. RESULTS: Recurrences occurred in 124 patients (50.8%). Of 185 patients who did not have a recurrence for the first 3 years, subsequent recurrences occurred in 65 patients; in more than half the first recurrence developed after 5 years or more. Ta tumors had a low recurrence rate (14.5%) with the first recurrence often developing after a long recurrence-free period. Of 40 patients who remained recurrence-free for 3 years or more after at least one recurrence occurred, 16 patients (40%) had subsequent recurrences. Furthermore, most of these patients who remained free of recurrence for more than 5 years eventually had a recurrence. The overall progression rate was 15.6%, and this did not relate to the length of the recurrence-free interval. CONCLUSION: When patients did not have a recurrence for the first 3 years, tumors subsequently often recurred, even in pTa tumors. In patients with at least once recurrence, subsequent recurrences appear to occur irrespective of the length of the recurrence-free period. Thus, we recommend that all patients with superficial bladder tumors be followed for as long as possible.     

Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: A retrospective multicenter study

AIM: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. METHODS: A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. RESULTS: The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level < or =20 ng/mL, Gleason score < or =7, and time to nadir PSA < or =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. CONCLUSIONS: The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.     

Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome

Summary. Acute megakaryoblastic leukaemia (M7) and transient myeloproliferative disorder in Down's syndrome (TMD) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers. To clarify properties of the blast cells in M7 and TMD cases, we examined erythroid markers expression in blasts from six cases with M7 and seven cases with TMD in this study. Erythroid-specific mRNAs encoding 7-globin and erythroid 6-aminolevulinate synthase were found to be expressed in blasts from most of these cases, indicating that majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes. We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in all these cases. These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells.     

High prevalence of antibodies to recombinant CENP-B in primary biliary cirrhosis: Nuclear immunofluorescence patterns and ELISA reactivities

The purpose of the present study is to evaluate the centromeric pattern on human laryngeal tumour (HEp-2) cells by indirect immunofluorescent (IIF) test and to compare their reactivities with a newly developed recombinant centromere protein B enzyme linked immunosorbent assay (CENP-B ELISA) test using sera of antinuclear antibody (ANA)-reactive primary biliary cirrhosis (PBC) patients. Antimitochondrial antibody (AMA) subtypes (PDC-E2, BCOADC-E2, OGDC, protein X, and PDC-E1α) by Western blot were also investigated to see whether they have any effect on the expression of CENP-B reactivities. A centromeric pattern (anticentromere antibody [ACA]) was detected in 11 of 25 (44%) PBC patients whereas CENP-B reactivity was found in 15 (60%) of them. There were some differences in IIF patterns and CENP-B reactivities. One PBC serum with indistinguishable ANA pattern reacted with CENP-B. Eight of 15 (53%) CENP-B reactive patients had other autoimmune-like disorders. Of 181 healthy sera, none was reactive for ACA either by IIF or by ELISA test. There was a correlation between ACA IIF and CENP-B ELISA titres (r= 0.824, P < 0.001). However, no correlation was observed between either CENP-B or AMA reactivities and/or between either autoantibodies or laboratory and histologic indices of PBC. These findings suggest that recombinant CENP-B ELISA appears to be more sensitive in identifying ACA than IIF, underlying its potential value as a screening test for the diagnosis of PBC complicated with other autoimmune-like disorders. The presence of multiple autoantibodies in PBC sera may reflect heterogeneous antigens recognition, and requires further study to identify target antigens at cellular and molecular levels.     

Ten cases of congenital urethral stricture in childhood with enuresis

BACKGROUND: To report short-term clinical outcomes of endoscopic correction of congenital urethral stricture in 10 boys who suffer from enuresis resistant to conservative therapy. METHODS: Fifteen boys ranging between 5 and 15 years old consulted our clinics for nocturnal and diurnal enuresis which had not been improved by medication and behavioral therapy. Among them, voiding cystography revealed bulbar narrowing (Cobb's Collar) in 10 cases and vesico-ureteral reflux was found in four cases (seven ureters). Endoscopically, this lesion was recognized as a ring-form stenosis just distal to the urethral sphincter. It was incised with infantile urethrotome. RESULTS: Vesico-ureteral reflux was resolved in four ureters and improved in one. In all cases, daytime enuresis resolved dramatically and night enuresis became controllable. CONCLUSIONS: Boys who suffer from diurnal enuresis should immediately be explored for the existence of congenital urethral stenosis. Early resolution may bring about better urinary behavior.