Secretory IgA accumulated in the airspaces of idiopathic pulmonary fibrosis and promoted VEGF, TGF-ß and IL-8 production by A549 cells.

Secretory IgA (SIgA) is a well-known mucosal-surface molecule in first-line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non-IPF subjects. An in-vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß and interleukin (IL)-8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA-induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF-ß and IL-8.

Secretory immunoglobulin A induces human lung fibroblasts to produce inflammatory cytokines and undergo activation.

Immunoglobulin (Ig)A is the most abundant immunoglobulin in humans, and in the airway mucosa secretory IgA (sIgA) plays a pivotal role in first-line defense against invading pathogens and antigens. IgA has been reported to also have pathogenic effects, including possible worsening of the prognosis of idiopathic pulmonary fibrosis (IPF). However, the precise effects of IgA on lung fibroblasts remain unclear, and we aimed to elucidate how IgA activates human lung fibroblasts. We found that sIgA, but not monomeric IgA (mIgA), induced interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production by normal human lung fibroblasts (NHLFs) at both the protein and mRNA levels. sIgA also promoted proliferation of NHLFs and collagen gel contraction comparable to with transforming growth factor (TGF)-ß, which is involved in fibrogenesis in IPF. Also, Western blot analysis and real-time quantitative polymerase chain reaction (PCR) revealed that sIgA enhanced production of α-smooth muscle actin (α-SMA) and collagen type I (Col I) by NHLFs. Flow cytometry showed that NHLFs bound sIgA, and among the known IgA receptors, NHLFs significantly expressed CD71 (transferrin receptor). Transfection of siRNA targeting CD71 partially but significantly suppressed cytokine production by NHLFs co-cultured with sIgA. Our findings suggest that sIgA may promote human lung inflammation and fibrosis by enhancing production of inflammatory or fibrogenic cytokines as well as extracellular matrix, inducing fibroblast differentiation into myofibroblasts and promoting human lung fibroblast proliferation. sIgA's enhancement of cytokine production may be due partially to its binding to CD71 or the secretory component.

Evaluation of the relationship between salivary concentration of anti-heat shock protein immunoglobulin and clinical manifestations of Behçet's disease.

OBJECTIVE: This study investigated the relationship between the concentration of anti-heat shock protein (HSP) 60 antibody in resting saliva and the severity of Behçet's disease (BD). METHOD: Sixty-five patients diagnosed with BD at Tokyo Medical and Dental University Hospital were enrolled in this study. Based on clinical severity scores, patients were categorized as having mild, moderate, or severe BD. Periodontal status was evaluated with the Community Periodontal Index (CPI), and anti-HSP60 antibody concentrations in resting saliva were measured with an enzyme-linked immunosorbent assay. RESULTS: The mean antibody concentration in patients in the moderate group was significantly higher than concentrations in the mild and severe groups. No significant difference was found between the mild and severe groups. Gingival inflammation, identified with the CPI, was associated with a higher antibody concentration. The antibody concentration in patients who had stomatitis for more than 2 weeks was significantly higher than in those with stomatitis for less than 2 weeks. The antibody concentration in patients who had taken colchicine was significantly lower than that in subjects who had not. CONCLUSION: These results suggest that the concentration of anti-HSP60 antibody in resting saliva may be effective as a non-invasive indicator for the diagnosis (screening) and prognostication of BD.

Involvement of brown adipose tissue in subcutaneous fat necrosis of the newborn.

BACKGROUND: Subcutaneous fat necrosis (SCFN) of the newborn is a rare condition that manifests within days after birth. The interscapular region, axillae and shoulders are the most commonly affected sites, corresponding to anatomic sites of brown adipose tissue (BAT) in newborns. OBJECTIVE: We postulated a specific involvement of BAT in SCFN and searched for brown adipocytes at affected sites. METHODS: Biopsy specimens were immunostained with antibodies against uncoupling protein 1 (UCP-1) and examined by electron microscopy. We also examined BAT by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and computed tomography (PET-CT) scanning. RESULTS: A few cells in biopsy specimens from two patients bound antibodies against UCP-1, and brown adipocytes were detected at several stages of degeneration. PET-CT scans revealed lower uptake of (18)F-FDG at major sites of SCFN. CONCLUSION: SCFN and BAT can be found at the same sites, suggesting a pathophysiological connection.

Pure laparoscopic hepatectomy for hepatocellular carcinoma patients with severe liver cirrhosis.

Hepatocellular carcinoma often arises in cirrhotic livers. Patients with severe liver cirrhosis who undergo hepatectomy often develop postoperative liver failure, even if the hepatectomy is limited. Here, we report six patients with severe liver cirrhosis (Child-Pugh B/C and indocyanine green retention rate at 15 min ≥ 40%) who underwent pure laparoscopic hepatectomy. Their perioperative course was favorable and comparable to that of other hepatocellular carcinoma patients with mild-moderate liver cirrhosis. In patients with severe liver cirrhosis, pure laparoscopic hepatectomy minimizes the disturbance in collateral blood and lymphatic flow caused by laparotomy and liver mobilization, as well as the mesenchymal injury caused by compression of the liver. It limits complications such as massive ascites, which can lead to severe postoperative liver failure. Good candidates for the procedure include patients with severe liver cirrhosis who have tumors on the liver surface and in whom adaptation to ablation therapy is difficult and/or who experience local recurrence after repeat treatments.

Successful treatment by double-filtration plasmapheresis of a patient with bullous pemphigoid: effects in vivo on transcripts of several genes for chemokines and cytokines in peripheral blood mononuclear cells.

The involvement of various cytokines and chemokines has been reported in the pathogenesis of bullous pemphigoid (BP). Double-filtration plasmapheresis (DFPP) is an effective treatment for BP but the mechanism of action remains unclear. Using semiquantitative reverse transcription-polymerase chain reaction, we examined levels of transcripts for various cytokines and chemokines in freshly isolated peripheral blood mononuclear cells in a patient with BP before and after DFPP treatment. DFPP was performed four times. Relative levels of transcripts for interleukin (IL)-8, macrophage inflammatory protein (MIP)-1alpha and IL-5, and the ratio of relative levels of transcripts for IL-4 and interferon (IFN)-gamma, were higher, before treatment, than in healthy controls, and decreased when the extent of the lesions was reduced. Relative levels of transcripts for tumour necrosis factor (TNF)-alpha and IL-4 also decreased with regression of lesions, although they were similar to or lower than the corresponding levels in healthy individuals. When eruptions recurred, relative levels of transcripts for IL-8, MIP-1alpha, RANTES (regulated upon activation normal T cell expressed and secreted), IL-2, IFN-gamma and TNF-alpha were very much higher than those prior to the recurrence, while relative levels of mRNAs for IL-4 and IL-5 did not increase. Relative levels of transcripts for IL-8, MIP-1alpha, TNF-alpha and IL-2 were lower at the end of each individual DFPP and after the four treatments than at the beginning of treatment. Our observations suggest that cytokines and chemokines produced in mononuclear cells play important roles in the pathogenesis of BP and that regulation of their expression might be involved in the therapeutic effects of DFPP in BP.

Changes in sodium transport in epithelial cells in a rat ileal-augmented bladder model.

OBJECTIVE: To investigate changes in the morphology and sodium transport ability of intestinal epithelium diverted to the urinary tract, using an in vitro sodium-binding benzofuran isophthalate (SBFI) technique, as the effects of long-term urine exposure on the transport of electrolytes through intestine are incompletely understood. MATERIALS AND METHODS: Ileal augmentation cystoplasty was conducted in female Sprague-Dawley rats; at 3 and 12 months after surgery the serum concentration of sodium, chloride and potassium were measured. Sodium transport in the ileal epithelial cells diverted to the urinary tract was evaluated using SBFI, as the value of the 340/380 nm excitation ratio measured with fluorescence spectrophotometry. The villous height and the number of villi per ileal length were obtained from haematoxylin and eosin-stained sections. RESULTS: After 3 months the mean (sd) serum sodium concentrations in normal and augmented rats were 140.4 (2.5) and 140.7 (3.5) mmol/L, respectively; the chloride concentration in normal rats was 97.0 (2.9), and in augmented rats at 3 and 12 months it was 102.4 (2.9) and 99.0 (3.7) mmol/L, respectively. At 3 months, chloride concentrations were significantly higher in augmented than in normal rats (P < 0.05). The mean (sd) 340/380 nm ratio increased by 0.85 (0.09) in the normal ileum, and by 0.73 (0.15) and 0.49 (0.23) in the ileum of augmented rats at 3 and 12 months, respectively; the difference between normal and augmented ileum at 12 months was significant (P < 0.05). At 12 months the villous height in the augmented ileum, at 227.6 (16.0) micro m, was significantly less than in the normal ileum, at 803.4 (66.2) micro m (P < 0.05). However, the number of villi/mm ileum in normal and augmented rats at 12 months was 13.7 (1.5) and 15.0 (0.8), respectively, and not significantly different. CONCLUSION: Sodium transport decreased significantly after long-term exposure to urine; the improvement in metabolic change was probably attributable to alterations of electrolyte transport and atrophic changes of the villus.

Health-related quality of life after radical cystectomy for bladder cancer: a comparison of ileal conduit and orthotopic bladder replacement.

OBJECTIVE: To compare the health-related quality of life (HRQoL) after radical cystectomy in patients with an ileal conduit or an orthotopic neobladder. PATIENTS AND METHODS: The study included 85 men who underwent radical cystectomy for bladder cancer, comprising 48 with an orthotopic neobladder (26 with an ileal and 22 with a colon neobladder) and 37 with an ileal conduit. HRQoL was evaluated using the Short Form-36 survey containing 36 questions assessing eight aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. RESULTS: The mean follow-up periods for patients with a neobladder (ileal and sigmoid) and with an ileal conduit was 45.9 (38.2 and 53.1, respectively) and 130.9 months, respectively. Scale scores were not affected by the duration of follow-up in either group. There was no significant difference in any scale scores between the neobladder and ileal conduit groups. However, general health and social functioning in both the neobladder and ileal conduit groups appeared to be significantly lower than those in the general population in the USA. Furthermore, patients with a colon neobladder had a significantly higher score for role-emotional functioning than those with an ileal neobladder, while there was no significant difference in the remaining seven scores between patients with ileal and colon neobladders. CONCLUSIONS: Six of the eight scales of HRQoL were favourable in both patients with a neobladder or an ileal conduit, and there was no significant difference between these groups. In addition, the HRQoL of patients with an orthotopic neobladder (except for role-emotional functioning) was unaffected by the segment of the intestine used for neobladder construction. Therefore, patients with both types of urinary diversion were generally satisfied with their overall health and quality of life.

Significance of prostate-specific antigen--alpha(1)-antichymotrypsin complex for diagnosis and staging of prostate cancer.

OBJECTIVE: To evaluate the clinical significance of measuring the prostate-specific antigen-alpha(1)-antichymotrypsin (PSA-ACT) for differentiating prostate cancer from benign prostate hypertrophy (BPH) and for the staging of prostate cancer. METHODS: Before treatment, total PSA (tPSA) and PSA-ACT were measured in 120 patients with prostate cancer and in 150 patients with BPH using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, the tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. RESULTS: tPSA, PSAD, PSA-ACT and ACTD levels in patients with prostate cancer paralleled the clinical stage and were significantly higher than those in patients with BPH. Furthermore, these four values were significantly higher in patients with pathologically extraprostatic disease than those with organ-confined disease. Receiver operating characteristics analysis among patients with PSA values of 4.1-10 ng/ml revealed that the areas under the curve for tPSA and ACTD were similar to those for PSA-ACT and ACTD, respectively and that no significant differences in the differentiation between prostate cancer and BPH were observed among these parameters. CONCLUSIONS: Measurement of PSA-ACT provides useful information for the clinical staging of prostate cancer and differential diagnosis between prostate cancer and BPH; however, compared with tPSA, PSA-ACT may not be significantly superior in the diagnosis and staging of prostate cancer.

Over expression of inhibitor of caspase 3 activated deoxyribonuclease in human renal cell carcinoma cells enhances their resistance to cytotoxic chemotherapy in vivo.

PURPOSE: We determined whether inhibitor of caspase-3 activated deoxyribonuclease (ICAD) enhances resistance to apoptotic stimuli or inhibits DNA fragmentation by inactivating caspase-3 activated deoxyribonuclease. MATERIALS AND METHODS: The liposome mediated gene transfer method was used to introduce ICAD complementary DNA into ACHN cells and the expression of ICAD protein per clone was evaluated by Western blot analysis. Effects of cisplatin treatment on growth inhibition and apoptosis in the ACHN sublines were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, DNA fragmentation assay and Western blot analysis of poly(ADP-ribose) polymerase protein. The limiting dilution assay was also performed to examine the effect of cisplatin treatment under anchorage independent conditions. Furthermore, nude mice bearing the ACHN sublines were given intraperitoneal injection of 5 mg./kg. cisplatin 1 and 2 weeks after the implantation of tumor cells and changes in tumor volume was measured. RESULTS: ICAD transfected ACHN cells inhibited DNA degradation after cisplatin treatment but not control vector only transfected ACHN cells, whereas a similar degree of apoptotic cell death induced by cisplatin in ICAD and control vector only transfected ACHN cells was observed on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Western blot analysis of poly(ADP-ribose) polymerase protein. However, the limiting dilution assay revealed that ICAD transfected ACHN cells had high resistance to pretreatment with cisplatin compared with control vector only transfected ACHN cells. Moreover, although there was no significant difference in the in vivo growth of ACHN sublines, cisplatin treatment induced the elimination of control vector only transfected ACHN cell tumors. In contrast, most ICAD transfected ACHN cell tumors continued to grow after cisplatin treatment. CONCLUSIONS: These findings suggest that when ICAD is over expressed in tumor cells, it renders them highly resistant to therapy induced apoptosis, resulting in enhanced tumor progression.

Role of percutaneous image-guided biopsy in the evaluation of renal masses.

OBJECTIVE: The objective of the present study was to evaluate the indications, accuracy, complications and impact of image-guided percutaneous biopsy of renal masses. MATERIALS AND METHODS: Between 1994 and 1999, percutaneous biopsies under ultrasonography or computerized tomography guidance were performed in 33 patients with renal mass (22 men and 11 women, mean age 57.5 years, range 21-88). We retrospectively analyzed the relationship between clinical and histopathological findings, and discuss the appropriateness of the indications for image-guided percutaneous biopsy in the diagnosis of renal masses. RESULTS: The indications used in our institution were as follows: (1) clinical and radiological findings to suggest a diagnosis other than primary renal cell carcinoma (RCC) (n = 15); (2) suspicious lesions of RCC in multiple cystic renal masses (n = 7); (3) differentiation of transitional cell carcinoma of the renal pelvis from RCC (n = 7); (4) differentiation of angiomyolipoma from RCC (n = 4). Sufficient amounts of tissues were obtained from all patients for pathological diagnosis. Among 33 patients, 21 (63.6%) were diagnosed positive for malignancy, and 15 underwent surgical intervention. The histopathological findings between percutaneous biopsy and surgically resected tissue were identical in 13 cases (86.7%). No patient developed major complications requiring surgical treatment. CONCLUSION: If performed under appropriate selection of patients, percutaneous image-guided biopsy is a safe, reliable and accurate method of managing suspicious and/or indeterminate renal mass, and may contribute to the selection of appropriate clinical management by avoiding unnecessary procedures.

Prognostic variables in patients who have undergone radical cystectomy for transitional cell carcinoma of the bladder.

OBJECTIVE: To evaluate whether several clinicopathological factors could be used as prognostic predictors in patients who have undergone radical cystectomy for transitional cell carcinoma (TCC) of the bladder. METHODS: Between January 1985 and June 2000, 154 patients underwent radical cystectomy and pelvic lymphadenectomy for TCC of the bladder at a single institution. Their clinicopathological findings were analyzed based on the criteria of the Japanese Urological Association. RESULTS: Histopathological examination revealed that the tumor grade was 1 or 2 in 22 patients and 3 in 132 patients; the pathological stage was pT1 or less in 30 patients, pT2 in 51 patients, pT3 in 53 patients and pT4 in 20 patients. Vascular involvement and lymph node metastasis were found in 85 and 33 patients, respectively. The cause-specific 5-year survival rate was 64.2% for all patients, 74.4% for patients with grade 1 or 2 tumors, 62.9% for those with grade 3 tumors; 90.9% for those with stage pT1 or less, 77.9% for those with stage pT2, 45.0% for those with stage pT3 and 29.2% for those with stage pT4 (p < 0.001); 83.2% for patients without vascular involvement and 42.0% for those with vascular invasion (p < 0.001); and 76.5% for patients without lymph node metastasis and 22.7% for those with lymph node metastasis (p < 0.001). Multivariate analysis revealed a strong independent correlation of the pathological stage and lymph node metastasis with poor prognosis and, furthermore, the incidence of lymph node metastasis was significantly related to the increase in pathological stage. CONCLUSIONS: In this series, the pathological stage, lymph node metastasis and vascular involvement, but not tumor grade, were significantly useful prognostic factors in patients who have undergone radical cystectomy for TCC and among them only pathological stage and lymph node metastasis could be used as independent predictors for poor prognosis.

Usefulness of Ureteropyeloscopy for diagnosis of upper urinary tract tumors.

BACKGROUND: Upper urinary tract tumors have historically been diagnosed using urinary cytology examination and radiography. As the technique and instrumentation of ureteroscopic inspection and biopsy have advanced, ureteroscopic examination has become more routine. We studied the applicability and safety of using ureteropyeloscopy to diagnose upper urinary tract tumors. PATIENTS AND METHODS: Between January 1994 and October 1999, 50 patients at Kobe University Hospital underwent ureteropyeloscopy for suspected upper urinary tract tumors. RESULTS: The sensitivity values of radiography, urinary cytology, and ureteroscopy were 96%, 60%, and 92%, respectively. The specificity values of the three procedures examination were 12%, 84%, and 88%, respectively. No major complications or dissemination of malignant cells were evident. CONCLUSION: Ureteroscopic examination is a safe, sensitive, and specific means of detecting upper urinary tract tumors.

Increased Fas ligand expression in the tumor tissue and serum of patients with testicular germ cell tumors with seminomatous elements.

OBJECTIVES: To measure the expression levels of Fas and Fas ligand (FasL) in testicular germ cell tumor (TGCT) and to determine whether the serum level of soluble FasL (sFasL) could be used as a marker for patients with TGCT. METHODS: The expression of Fas and FasL in 51 specimens obtained from patients with TGCT was examined by reverse transcriptase-polymerase chain reaction, and the results were confirmed by Western blot analysis. The serum levels of sFasL in 24 patients with TGCT were measured using an enzyme-linked immunosorbent assay system. RESULTS: Of 33 TGCT specimens that included seminomatous elements, Fas and FasL was expressed in 24 (73%) and 24 (73%), respectively. On the other hand, 10 (56%) and 2 (11%) specimens expressed Fas and FasL, respectively, in 18 TGCT specimens without seminomatous elements. Moreover, the serum levels of sFasL were significantly higher in patients with TGCT with a seminomatous element than in those without it. CONCLUSIONS: These results indicate that FasL is strongly expressed in tumor tissue and is present at high levels in the serum of patients with TGCT with a seminomatous element compared with those without it and that the serum levels of sFasL could be used as a novel diagnostic marker for TGCT with seminomatous elements.

Cutaneous necrosis after superficial temporal artery-to-middle cerebral artery anastomosis: is it predictable or avoidable?

OBJECTIVE: This study was carried out to determine whether a relationship exists between cutaneous necrosis after superficial temporal artery-to-middle cerebral artery anastomosis and background risk factors or surgical methods, and to determine whether such necrosis is predictable or avoidable. METHODS: Forty-seven patients (a total of 51 sides) with atherosclerotic lesions of the internal carotid artery or middle cerebral artery who underwent superficial temporal artery-to-middle cerebral artery anastomosis at the National Kyushu Medical Center Hospital between September 1, 1994, and August 31, 1999, were reviewed. Each procedure was analyzed to determine whether cutaneous necrosis was present postoperatively around the donor site, whether preexisting risk factors (hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, and arteriosclerosis obliterans) were present, and whether a flap or cutdown method or a single or double anastomosis was performed. RESULTS: Postoperative necrosis was clearly related to arteriosclerosis obliterans (P < 0.003). The tendency for a relationship between necrosis and smoking was noted. Although statistical analysis failed to demonstrate a significant difference, necrosis was found with the flap method but not with the cutdown method. CONCLUSION: Further study is needed using greater numbers to clarify the relationship between the surgical method and the presence of necrosis. To prevent cutaneous necrosis, however, it may be preferable to use the cutdown method in patients with the preexisting risk factors of arteriosclerosis obliterans or in smokers.

Y-chromosome microdeletion and phenotype in cytogenetically normal men with idiopathic azoospermia.

OBJECTIVE: To determine the prevalence of microdeletions of the long arm of chromosome Y within the AZFa, AZFb, and AZFc subregions in patients with idiopathic azoospermia, and then correlate the microdeletions with clinical phenotypes to determine the most important subregion for screening. DESIGN: Controlled clinical study. SETTING: Male infertility clinic, Kobe University Hospital. PATIENT(S): Among 89 consecutive azoospermic patients, those whose infertility was related to known hereditary, endocrine, or obstructive causes or a cytogenetic abnormality were excluded; 54 remaining patients were studied using a polymerase chain reaction (PCR). Of these patients, 33 had Sertoli cell only syndrome, 10 had maturation arrest, and 11 had hypospermatogenesis. INTERVENTION(S): Blood and semen samples and testicular biopsies were obtained from all of the participants. MAIN OUTCOME MEASURE(S): We performed semen analysis, polymerase chain amplification of 28 DNA loci on the long arm of the Y chromosome involving the DAZ (deleted in azoospermia), and measured the plasma FSH, LH, testosterone, prolactin, and estradiol levels. RESULT(S): Microdeletions were detected in 14 of the 54 patients (nine with Sertoli cell only, three with maturation arrest, and two with hypospermatogenesis). Most microdeletions involved AZFb or AZFc. Patients with hypospermatogenesis or maturation arrest showed deletion only in AZFc. The DAZ gene was deleted in four patients with Sertoli cell only and one patient with maturation arrest. The RBM gene was deleted in two patients with Sertoli cell only who had particularly large deletions, but in no patients with arrest or hypospermatogenesis. CONCLUSION(S): Cytogenetically azoospermic patients should be examined for microdeletions before undertaking assisted reproduction. AZFc may be the most important subregion to screen. In addition, intact AZFa and AZFb subregions may be important for the presence of germ cells.

Significance of serum inhibin B concentration for evaluating improvement in spermatogenesis after varicocelectomy.

BACKGROUND: The study aim was to clarify the relationship of serum inhibin B concentrations to recovery of spermatogenic function after varicocelectomy, both as a predictor of improvement in the seminogram and as a means of monitoring hormonal function after surgery. METHODS: Fifty-two varicocele patients, including five with normal sperm concentrations, were studied. Changes in the seminogram, serum hormone concentrations and serum inhibin B were evaluated in the 47 oligozoospermic patients after surgery. Preoperative inhibin B concentrations correlated significantly with serum concentrations of FSH (r = 0.598, P < 0.0001) and testosterone (r = 0.380, P < 0.02). Inhibin B concentrations also correlated significantly with sperm concentration (r = 0.351, P < 0.02) and total testicular volume (r = 0.578, P < 0.0001). No significant correlation was seen between inhibin B and the Johnsen score. Preoperative concentrations of inhibin B were higher in patients who increased their sperm concentration after surgery (responders) than in those without improved concentrations (non-responders). No significant difference was observed between pre- and postoperative inhibin B concentrations in responders or non-responders. However, 15 of 25 (60%) patients with increased inhibin B showed improvement of the seminogram, while only five of 22 (23%) patients with no change or a decrease in inhibin B had any improvement (P < 0.05). CONCLUSIONS: Preoperative serum inhibin B concentration could not reliably predict a response to varicocelectomy. However, a change in serum inhibin B concentration after varicocelectomy might be helpful to evaluate the improvement of testicular function after varicocelectomy.

Long-term results of neoadjuvant hormonal therapy prior to radical prostatectomy in patients with clinically localized prostate cancer: biochemical and pathological effects.

The objective of this study was to evaluate the long-term biochemical and pathological effects induced by neoadjuvant hormonal therapy (NHT) in patients with clinically localized disease. Between March 1993 and May 1997, 24 patients with clinically localized prostate cancer received NHT for 3 to 11 months (median: 5 months) using luteinizing hormone-releasing hormone analogue prior to radical prostatectomy and pelvic lymphadenectomy. The clinical stage was T1 in 1 patient, T2 in 17 and T3 in 6, the pretreatment serum prostate-specific antigen (PSA) value was < or = 10 ng/ml in 5 patients, 10 to 20 ng/ml in 4 and > 20 ng/ml in 15 (mean: 34.7 micrograms/l), and the Gleason score was < or = 4 in 9 patients, 5 to 7 in 11 and > 8 in 3. The mean prostate specific antigen (PSA) value 3 months after NHT had reduced below 2 ng/ml in 18 of the 24 patients (67%), and finally decreased by an average of 95% (i.e., 1.9 ng/ml) prior to surgery. The pathological stage was pT0 in 2 patients, pT2 in 10 and pT3 in 12. The incidence of organ-confined disease (OCD) was significantly higher in patients with clinical stage T1 or T2a than with T2b or T3, with pretreatment PSA values < or = 10 ng/ml than with PSA values > 10 ng/ml, and with PSA values < or = 2 than with PSA values > 2 at 3 months after NHT; in contrast, the Gleason score had no significant impact on the rate of OCD. After a median follow-up of 49 months (range 34 to 85 months), 6 patients (25%) had a recurrence evidenced by rising PSA, and the 3-year recurrence-free survival rate was 79%. These results suggest that NHT appears not to be of significant additional benefit to patients who have a higher clinical T stage, higher pretreatment PSA values and/or in patients whose PSA values do not normalize early in the treatment process.