Hyperbaric oxygen therapy for radiation cystitis in patients with prostate cancer: a long-term follow-up study.

OBJECTIVE: To assess the safety and efficacy of hyperbaric oxygen (HBO) for treating radiation cystitis a long-term follow-up study was done in patients with prostate cancer, the second most common malignancy in Japan. PATIENTS AND METHODS: A total of 38 patients at an age of 68 ± 8 years with radiation cystitis following irradiation of prostate cancer were treated with HBO at 2 absolute atmospheric pressures for 90 min daily. The average number of HBO treatment sessions in each patient was 62 ± 12. The follow-up period was 11.6 ± 3.7 years. We evaluated objective and subjective symptoms periodically with special reference to the initiation timing of HBO therapy. RESULTS: High efficacy ratios of objective and subjective findings were obtained at 2 and 4 (79-95%) years, respectively. After 7 years' follow-up, these ratios decreased slightly (72-83%) but still remained stable thereafter (75-88%) without any serious accident. Comparison of late morbidity scores before and 11.6 years after HBO therapy showed significant improvement (p < 0.0005). Twenty-eight patients (74%) obtained nonrecurrent outcome. They had received 18% lower (p < 0.001) radiation dosage than recurrent patients. The interval between the onset of hematuria and start of HBO treatment in nonrecurrent patients was 30% shorter (p < 0.001) than that of recurrent patients. CONCLUSIONS: We elucidated the long-term safety and beneficial effect of HBO therapy of radiation cystitis in patients with prostate cancer. Early application of HBO treatment after the onset of hematuria appears to produce favorable outcome.

p53 antibodies in the serum of patients with prostate cancer.

UNLABELLED: We assessed the potential clinical utility of levels of p53-specific antibodies as a novel serum biomarker of prostate cancer that could be used in conjunction with level of PSA. MATERIAL AND METHODS: Serum levels of p53-specific antibodies in patients with relapsed, newly diagnosed prostate cancer and in patients with benign prostate hyperplasia were quantified by an enzyme-linked immunoabsorbent assay. RESULT: There was no significant difference (P=0.96) between the serum levels of p53-specific antibodies in patients with newly diagnosed prostate cancer and with benign prostatic hyperplasia. In the newly diagnosed prostate cancer group, stage T1c (n=8) showed the lowest p53-specific antibody level. However, the difference between T1c group and benign prostatic hyperplasia group was not significant (P=0.686). The relapsed cancer group tended to have low levels of the antibodies, and, there was no significant difference between the relapsed prostate cancer group and the benign prostatic hyperplasia group (P=0.14). The serum levels of p53-specific antibodies in patients with metastatic and with localized prostate cancer showed no significant difference (P=0.68). CONCLUSION: The use of titers of p53-specific antibodies to make differential diagnosis between prostate cancer and benign prostatic hyperplasia might have no role, and the antibodies should not be used as a marker of prostate cancer by itself. Because our study is based on small number of patients, further studies are necessary before its absolute validity can be determined.

Absence of Bcl-2 expression favors response to the short-term administration of diethylstilbestrol diphosphate in prostate Cancer.

BACKGROUND: Neoadjuvant hormone therapy remains a controversial issue in spite of multiple studies having been performed. METHODS: We performed short-term (10 days) treatment with diethylstilbestrol (DES) in 30 patients with stages T2 or T3 prostate cancer (PCa). All the patients underwent needle core prostate biopsy before and radical prostatectomy within a month after the start of the endocrine therapy. The histological effects in PCa and the changes in morphological and clinical parameters and their association were elucidated. RESULTS: Serum PSA (P < 0.001), Ki-67 PI (P = 0.022), and AR (P = 0.002) expression decreased after the treatment. An obvious effect (Grade 1-3) of endocrine treatment was seen in 11 of 30 patients and was associated with a prominent PSA decrease (P = 0.0274) and with older age (P = 0.0026). Pre-treatment specimens from a group without any effects of endocrine therapy had a higher frequency of Bcl-2 positivity (57.9%) compared to the group of Grade 1-3 effects (27.3%). Prostatectomy specimens presented with significantly higher AI in Bcl-2 negative cases (P = 0.0029) and pre treatment Bcl-2 was associated with a higher AI in Grade 1-3 patients (P = 0.0393). CONCLUSIONS: Older age is a predictor of histological effects in short-term hormone treatment of PCa. A lower Bcl-2 in biopsy specimens presented more frequently in the patients who experienced a prominent effect of endocrine therapy, and it was also useful to predict a significantly higher AI in Grade 1-3 patients. Histological effects are also associated with the PSA decrease, reflecting the clinically meaningful shrinkage of tumors and a decrease of tumor burden.

Therapeutic outcome of hyperbaric oxygen and basic fibroblast growth factor on intractable skin ulcer in legs: preliminary report.

BACKGROUND: Beneficial effects of hyperbaric oxygen on ischemic vascular diseases have been noted. Acceleration of wound healing with basic fibroblast growth factor has also been reported. The authors employed combination therapy of hyperbaric oxygen and basic fibroblast growth factor in patients with skin ulcer in legs refractory to conventional therapy. METHODS: Three men and four women were simultaneously treated with hyperbaric oxygen at 2 absolute atmospheric pressures for 90 minutes daily and spray treatment of basic fibroblast growth factor to the ulcer bed daily for an average of 2.6 months. Biopsy specimens obtained from ulcer tissues were divided into two pieces, one for histologic examination and the other for measuring fibrous protein. RESULTS: Ulcers were completely cured in five of seven patients. Two patients showed shrinkage of ulcer size. This combined therapy induced proliferation of connective tissue of the ulcer tissues, especially collagen and noncollagenous protein. CONCLUSIONS: Combined treatment with hyperbaric oxygen and basic fibroblast growth factor may be useful in patients with intractable skin ulcers in legs, and the shrinkage effect of this therapy is probably related to the proliferation of granulation tissues of the ulcer lesion.

c-Fos expression in the spinal cord after acute sacral segmental nerve stimulation.

AIMS: Sacral nerve stimulation (SNS) can provide subjective and objective relief of pelvic pain and chronic voiding symptoms, but its mechanism is poorly understood. It is well known that a noxious stimulus applied to one part of the body can reduce the response to a subsequent stimulus elsewhere in the body. This phenomenon, known as diffuse noxious inhibitory controls (DNIC), seems to be the mechanism by which pain can be reduced by concurrent noxious stimulation. METHODS: On the basis of the DNIC concept, we investigated the expression of a protein product of proto-oncogene c-Fos (c-Fos) in the rat spinal cord after acute electrical stimulation of the sacral segmental nerve with or without lower urinary tract irritation. Adult male Sprague-Dawley rats were treated either by sacral nerve stimulation (SNS) from the S1 sacral foramen or chemical irritation of the lower urinary tract (LUT) or both. Rats were perfused transcardially, and spinal cords were removed and processed for c-Fos immunohistochemistry. c-Fos expression in the central nervous system was detected by immunohistochemistry by using the avidin-biotin technique. The number of c-Fos-positive cells and their locations in the spinal cord were evaluated. RESULTS: SNS and LUT irritation resulted in significant increases in c-Fos-positive cells in L6 and S1 spinal segments. In the animals treated by SNS and LUT irritation, counts of c-Fos-positive cells in L6 and S1 segments were significantly smaller than expected. Distribution and number of c-Fos-positive cells in rats that received SNS and LUT irritation were almost the same as those induced by SNS alone in the S1 segment. CONCLUSIONS: SNS alone caused a near maximal response in c-Fos expression such that adding LUT irritation did not cause a linear increase in c-Fos. Subsequent LUT irritation could not induce additional expression of c-Fos within the spinal cord.

Localization and physiological implication of aldose reductase and sorbitol dehydrogenase in reproductive tracts and spermatozoa of male rats.

The polyol metabolizing pathway, which consists of two enzymes, aldose reductase (AR) and sorbitol dehydrogenase (SDH), converts glucose to fructose. The enzymatic activities, expression, and localization of AR and SDH were studied in reproductive tracts and spermatozoa of male rats by immunohistochemistry, Western blotting, and enzyme assays. Immunoreactivity to an AR antibody was observed mainly in epithelia of epididymis, seminal vesicle, vas deferens, and prostate gland in adult rats. Similar staining profiles were observed for these tissues when an SDH antibody was used. However, in testis, the cells that express these 2 enzymes differed; whereas AR was expressed in Sertoli cells and to lesser extent in spermatogenic cells, SDH was detected in spermatogenic cells of seminiferous tubules. This cell type-specific gene expression was confirmed in primary cultured cells isolated from rat testes. SDH protein levels were higher during spermatid elongation, and large amounts of SDH were carried over to the spermatozoa. Because one of the functions of members of the aldo-keto reductase superfamily is to detoxify harmful carbonyl compounds, an intrinsic function of AR in Sertoli cells may be to catalyze the reduction of cytotoxic metabolites, such as lipid peroxidation products and steroid hormones, which are produced during spermatogenesis. Because uterine fluid and seminal plasma both contain sorbitol, it is likely that SDH in spermatozoa converts sorbitol to fructose for use as an energy source.

Retroperitoneal schwannoma extending into the intravertebral foramen.

A 35-year-old Japanese man first visited the hospital for episodes of numbness in the right medial femoral region and loss of muscular strength in the right thigh. A CT scan of the abdomen showed a 10 x 9-cm well-circumscribed in homogeneous multilayered mass, in contact with the lumbar vertebrae. MRI demonstrated a hypodense and hyperdense mixed mass. Tumor extension into the L(2)/L(3) intravertebral foramen was shown. To avoid spinal cord damage, we chose enucleation of the tumor in the intravertebral foramen. A follow-up CT after 1 year showed no evidence of a recurrent mass. In conclusion, we advocate the nerve-sparing operation in cases like that of our patient.

Relationship between the shape of passive urethral resistance relation and prostatic histology in patients with benign prostatic hyperplasia.

We assessed the relationship between the type of passive urethral resistance relation (PURR) and prostatic histology in 28 patients with benign prostatic hyperplasia (BPH), who underwent transurethral resection of the prostate. PURR was classified into three types according to pressure-flow plots, and resected specimens were analyzed by quantitative morphometry. Patient age, prostatic volume and the area densities of each histological component did not show significant differences among the three groups. However, there was a trend to correlation between prostates with a high glandular component and urethral compliance. Further studies of larger populations are needed to validate this assumption.

Apoptosis and expression of apoptosis-related genes in the mouse testis following heat exposure.

OBJECTIVE: To investigate molecular mechanisms of germ cell apoptosis induced by heat exposure in mice. DESIGN: Controlled laboratory study. SETTING: Departments of Urology and Biochemistry, Yamagata University School of Medicine, Yamagata, Japan. ANIMAL(S): Forty-four male B6D2F1 mice. INTERVENTION(S): Heat exposure, 43 degrees C for 15 minutes. MAIN OUTCOME MEASURE(S): Testicular germ cell apoptosis (percentages of apoptotic tubules and apoptotic cells) was assessed by using DNA nick-end labeling, and expression of Bcl-2 family, Fas-FasL system, and p53 was evaluated by using Western analysis. RESULT(S): Bilateral testicular weights decreased significantly from 3 days after heat exposure. Percentages of apoptotic tubules and apoptotic germ cells increased significantly from 1 day after heat exposure. There were no significant changes in the levels of Bcl-xl, Bad, and Bax after heat exposure. However, Bcl-2 expression level decreased significantly 7 days after heat exposure. In contrast, the expression level of Fas and p53 increased significantly from 1 day to 3 days after heat exposure, respectively. Expression level of FasL elevated significantly at days 1 and 2 but declined from day 3. CONCLUSION(S): Germ cell apoptosis induced by heat exposure is mainly mediated by the Fas-FasL system.

Spinal substance P immunoreactivity is enhanced by acute chemical stimulation of the rat prostate.

OBJECTIVES: To investigate the role substance P (SP) plays in prostatic inflammation, we evaluated SP immunoreactivity within the spinal cord after irritation of the prostate. Because alpha-adrenergic blockade attenuates nociceptor-induced pain, the effects of an alpha-adrenergic blocker on SP immunoreactivity were also evaluated. SP is considered a mediator of nociception in the spinal cord. Immunoreactivity of SP is enhanced after acute chemical stimulation of somata. METHODS: Rats received chemical irritation of the prostate with or without pretreatment with tamsulosin. They were killed after 1 hour, and immunohistochemical staining for SP was performed. SP immunoreactive areas were quantified in the dorsal spinal cord of the L5 to S2 segments. RESULTS: Chemical irritation of the prostate increased SP immunoreactive areas in the L6 to S2 segments. Enhancement was observed in the whole dorsal spinal cord regions. This enhancement was significantly attenuated by tamsulosin in the L6 and S1 segments. CONCLUSIONS: SP probably plays a significant role in mediating nociceptive processing from the prostate. Tamsulosin can attenuate nociception-induced SP upregulation within the spinal cord.

Spinal NK1 receptor is upregulated after chronic bladder irritation.

It has been suggested that there is a significant upregulation of the NK1 receptor (NK1R) on neurons in the dorsal spinal cord after long-term somatic inflammation. This upregulation appears to play a significant role in central sensitization in chronic pain states. However, it is not clear whether such a change is also observed after chronic visceral (bladder) inflammation. Changes in NK1R immunoreactivity after chronic bladder irritation were investigated in order to evaluate the existence of hypersensitive states in the spinal cord after chronic bladder irritation. Experiments were performed on a total of 12 adult female Sprague-Dawley rats. In six animals, cyclophosphamide (CPA) was administered intraperitoneally for 2 weeks. Another six animals were given intraperitoneal saline injections and served as the control group. After these treatments, immunohistochemical staining for NK1Rs and substance P in rat lumbosacral spinal cord was performed. In CPA-treated animals, NK1R-positive areas and staining intensity within the dorsal spinal cord were significantly increased in the L5 to S2 spinal cord areas, especially in the L6 and S1 segments. In the L6 spinal segment, CPA-treatment enhanced NK1R immunostaining in the medial and the lateral dorsal horn, as well as in the lateral laminae including the sacral parasympathetic nucleus to a lesser extent. In CPA-treated animals, substance P staining intensity increased in the same regions in which NK1R immunoreactivity was increased. This finding probably implies the upregulation of spinal NK1R and the occurrence of central sensitization within the spinal cord after chronic visceral inflammation.