[Roles of BPH impact index in the evaluation of impaired urination in patients with BPH].

OBJECTIVE: To assess the significance and current status of the benign prostatic hyperplasia (BPH) impact index (BII) in the evaluation of subjective symptoms of impaired urination in so-called QOL disease, BPH. PATIENTS AND METHODS: Over the past 2 year-period, in 159 patients with the diagnosis of BPH were asked to reply to each of the international prostate symptom score (I-PSS), QOL index and BII questionnaires. The subjective symptom scores (a total of 246 points) were evaluated from the viewpoint of clinical statistics in the search for any these and to find which questions cover the BII, most. RESULTS: 1) Statistically significant but moderate correlations were observed among I-PSS total score, QOL index and BII. The correlations among Qmax, BII and QOL were very weak. 2) Out of the 11 domains in both IPSS and BII, 2 questions of BII ("bothersomeness caused by urinary problems" and "degree of worry about well-being") and 4 questions of IPSS ("residual sense," " pollakisuria," "weak urinary stream" and "nocturia") were shared as QOL indices. Patient satisfaction was affected also by the questions in the BII. 3) Of the 7 BPH symptoms assessed in IPSS, 4 symptoms ("residual sense," "pollakisuria," "weak urinary stream" and "nocturia") affected the QOL index, and 4 symptoms ("urgency on micturition," "residual sense," "nocturia" and "strain at urination") affected BII. 4) Of the 7 symptoms assessed by IPSS, different symptoms affected each of the 4 BII questions. CONCLUSION: It is needed to assess BPH symptoms not only by the IPSS and QOL index but also based on BII to provide the detailed therapeutic instructions and thorough patients consultation.

Sarcomatoid renal cell carcinoma with a chromophobe component producing beta-human chorionic gonadotropin.

We report a case of sarcomatoid renal cell carcinoma with a chromophobe component showing significant elevation of beta-human chorionic gonadotropin (beta-HCG) in the peripheral blood. A 35-year-old man was hospitalized because of a large tumor of the left kidney and elevated serum levels of beta-HCG. Extended nephrectomy was performed, after which the serum beta-HCG level decreased. However, 3 months later, masses were discovered in the left renal bed and in the lung in association with elevated serum levels of beta-HCG. The patient was rehospitalized and received combination therapy with interferon-alpha and doxorubicin-based multiple chemotherapy (cyclophosphamide, vincristine, doxorubicin, and dacarbazine). The recurrent mass responded extremely well to treatment, and beta-HCG normalized. However, the patient died 14 months after nephrectomy because of eventual resistance to chemotherapy. Sarcomatoid renal cell carcinoma containing beta-HCG positive cells were pathologically diagnosed with immunohistochemical staining in the left kidney. Sarcomatoid renal cell carcinoma is a variant of renal adenocarcinoma which has a poor prognosis. This patient had an extremely rare sarcomatoid renal cell carcinoma associated with serum levels of beta-HCG which were elevated and strongly correlated with morphologic cancer activity. beta-HCG might be a useful serum marker for detecting and monitoring this renal cell carcinoma.

[Invasive squamous cell carcinoma of the bladder: report of 18 cases and review of literature].

PURPOSE: This study was undertaken to determine the most effective treatment for improvement of the prognosis of patients with squamous cell carcinoma of the bladder (SCC). MATERIALS AND METHODS: The subjects included 18 cases of invasive SCC (T2 or worse) we have experienced in the past 10 years. While clarifying the clinical patterns of these cases, the association between stage, therapy, and prognosis was studied. Of the cases of invasive SCC reported in Japan in the recent 20 years, 54 cases in which the stage, therapy, and prognosis were documented were selected, and the association between the therapy and outcome in each stage was studied. RESULTS: In our series, 11 cases are alive without cancer for over 2 years. Of the above patients, 7 underwent cystectomy. Cancer death was experienced in 7 patients. Of these patients, 3 underwent cystectomy, and 6 were classified as stage III or higher. As far as our study of the cases reported in Japan is concerned, the prognosis of the cases having undergone TUR or partial resection of the bladder alone was poor. But, even if patients underwent cystectomy, most of the patients was cancer death in the cases whose cancer was stage III or higher. In the patients receiving some supportive therapy, 4 patients receiving radiation plus cisplatin-based chemotherapy were all alive without for over 2 years. CONCLUSIONS: Total cystectomy is most appropriate as the type of operation for the cases of invasive SCC. But, the cases whose cancer was stage III or higher have high recurrence rate, and must be accompanied with some supportive therapy. We concluded that radiation plus cisplatin-based chemotherapy is a candidate of most effective supportive therapy to improve the prognosis of those patients in the supportive therapy.

[Clinical characteristics of 16 patients suspected preclinical Cushing's syndrome].

PURPOSE: In 1996, Japanese guidelines for the diagnosis of preclinical adrenal Cushing's syndrome were proposed. However, several patients with preclinical Cushing's syndrome (PCS) didn't clearly show that these diagnostic guidelines were universally applicable. The aim of the present study was to evaluate the validity of these diagnostic guidelines on the basis of our clinical experience. PATIENTS AND METHODS: We performed adrenalectomy for adrenal incidentaloma in 16 patients with suspected PCS at our university hospital from 1990 through 2002. Eight patients met the Japanese criteria for the diagnosis of PCS (PC group) and 8 did not (dexamethasone [DXM] suppression group). Clinical characteristics and pathology profiles were compared between the groups. RESULTS: No patients in the DXM suppression group showed responses of serum cortisol levels on a 1-mg overnight dexamethasone suppression test. Twenty-four-hour urinary levels of 17-hydroxycorticosteroids were significantly higher in the PC group than in the DXM suppression group. In all patients of both groups, adrenal scintigraphy showed marked accumulation of radioisotope in the adhesive, atrophic adrenal cortex. One patient of the DXM suppression group had severe adrenal symptoms after adrenalectomy. Several patients in the DMX suppression group showed clinical improvement after adrenalectomy, as well as did several patients in the PC group. CONCLUSION: Endocrine activity may have been higher in the PC group than in the DXM suppression group. However, because patients who failed a 1-mg DXM suppression test may in fact have autonomous cortisol secretion, adrenalectomy may still be indicated. Autonomous cortisol secretion might not be documented with the 1-mg overnight DXM suppression test; therefore, the results must be interpreted carefully.

[Retrospective analysis of uroepithelial malignancies detected in the renal pelvis and ureter over the past decade at the Jikei University Hospital].

The aim of this study was to investigate recent characteristics and alterations of upper urinary tract cancer based on experience at a single institution over the past decade. Ninety-nine patients with renal pelvic and ureteral cancer resected at the Jikei University Hospital from January 1991 through December 2000 were retrospectively analyzed. Cancer-specific survival by pathologic stage, grade, and various clinical parameters were calculated by the Kaplan-Meier method. Prognostic factors for survival were examined with univariate and multivariate analysis. Cox regression analysis was used for multivariate analysis. Twenty-eight percent of cancers had been detected incidentally without having caused any symptoms. The overall 3-year and 5-year cancer-specific survival rates were 78% and 70%, respectively. The 5-year survival rate was 100% in patients with G1 cancer and 38% in those with G3 cancer. The 5-year survival rate was significantly higher in patients with cancers of lower grade (p = 0.0089), and was also higher in patients with cancers of stage pT1 or lower than in patients with cancers of stage pT2 and higher (p = 0.0038). The survival of patients with recurrence in the bladder was significantly longer than that of patients with recurrence in other organs. Multivariate analysis indicated that patient age and pT were the most important prognostic factors, followed by the presence of symptoms at diagnosis. The incidence of asymptomatic upper urinary tract cancer is increasing at institutions in Japan. We conclude that the cancer grade and stage still have classical predictive value, but that the presence of symptoms at the time of diagnosis is also an important prognostic factor.

Transactivation of epidermal growth factor receptor after heparin-binding epidermal growth factor-like growth factor shedding in the migration of prostate cancer cells promoted by bombesin.

BACKGROUND: A pathway consisting of bombesin, G-protein coupling receptors (GPCRs), metalloproteases, pro-heparin-binding epidermal growth factor (proHB-EGF), and epidermal growth factor receptor (EGFR) has been reported in prostate cancer cells. The occurrence of HB-EGF shedding from proHB-EGF in this pathway, however, has not been proven directly. In addition, it is still unclear how much this pathway contributes to the migration of prostate cancer cells. In this study, we tried to directly elucidate HB-EGF shedding in this pathway and to determine its contribution to the migration of prostate cancer cells. METHODS: RT-PCR and indirect immunofluorescence staining for HB-EGF and its receptors, such as EGFR and HER4/erbB4, were performed on PC-3 cells. The influences of bombesin, anti-EGFR neutralizing monoclonal antibody, HB-EGF, and HB-EGF shedding inhibitor on the migration of PC-3 cells were studied by means of in vitro wound assays. The amount of HB-EGF shed from PC-3 cells with alkaline phosphatase-tagged HB-EGF in the presence of bombesin was determined by measuring AP activity. Immunoprecipitations and phosphotyrosine Western blotting were performed to detect EGFR transactivated by bombesin. RESULTS: PC-3 expressed HB-EGF and EGFR, but not HER4/erbB4. PC-3 migrated in the presence of bombesin, but its migration was partly inhibited by the neutralizing antibody against EGFR. PC-3 also migrated in the presence of HB-EGF, but HB-EGF shedding inhibitor partly inhibited this phenomenon. HB-EGF was shed from PC-3 cells in the presence of bombesin, and this shedding was inhibited by HB-EGF shedding inhibitor. In addition, the EGFR on PC-3 was activated in the presence of bombesin and inactivated in the presence of HB-EGF shedding inhibitor. CONCLUSIONS: These results indicated that HB-EGF shedding and the following transactivation of EGFR occurs in this pathway and that this pathway partly contributes to the migration of prostate cancer cells.

[Bilateral pyeloureteritis cystica: a case report].

We report here a case of bilateral pyeloureteritis cystica. A 67-year-old woman was admitted to our hospital with asymptomatic macrohematuria in September 1999. Drip infusion pyelography and enhanced computed tomography demonstrated multiple small, round filling defects in both renal pelvises and ureters. Ureteroscopy and cold punch biopsy were performed, and histological examination revealed pyeloureteritis cystica. This patient was not given adjuvant therapy but was carefully followed up for 3 years and 6 months postoperatively.

Clinical studies on inverted papilloma of the urinary tract: report of 48 cases and review of the literature.

PURPOSE: We report on 48 clinicopathologic cases of inverted papilloma and present the clinical significance attributed to these lesions in terms of the current literature. MATERIALS AND METHODS: From 1976 to 2002 we had experience with 48 cases of inverted papilloma in urinary tract. We present the clinical features of these cases and report the results of prognosis research. RESULTS: Patient age ranged from 24 to 82 years (mean 56). Coexistence of transitional cell carcinoma occurred in a different location in the bladder in 3 cases and within a single neoplasm in the ureter in 2. Followup data were available in 42 of the 48 cases. Followup ranged from 8 months to 23 years 6 months (mean 8 years 1 month). Of the 42 cases 3 (7%) had a recurrence and range from initial resection at 5 months, 1 year 4 months and 2 years 6 months, respectively. CONCLUSIONS: Our study suggests that there are 2 types of urinary inverted papilloma. The lesions in 1 type behave in a benign fashion and in another they have malignant potential. At this time we have no strategy with which to distinguish the 2 types of urinary inverted papilloma. Our results indicate that we must follow all cases for at least more than 2 years after initial treatment.

Xanthogranulomatous cystitis.

Xanthogranulomatous cystitis (XC) is a rare benign chronic inflammatory disease of unknown etiology. Herein we report a case of a 70-year-old woman who presented with frequent, postmicturition pain and lower abdominal discomfort. Cystoscopy revealed a mass at the dome of the bladder near the left wall. Enhanced computed tomography (CT) demonstrated a mass with a central cavity. The patient underwent partial cystectomy because the presence of bladder neoplasm could not be ruled out. She had has no recurrence of XC 29 months after the operation. The present case of XC is the 20th to be reported in the world.

[Mucinous adenocarcinoma of the prostate: a case report and review of 32 cases on immunohistochemical study of both PSA and CEA].

Mucinous adenocarcinoma of the prostate is extremely rare and its biological behavior is not well known. We report a case of mucinous adenocarcinoma of the prostate which stained positively for prostate specific antigen (PSA) and negatively for carcinoembryonic antigen (CEA) on immunohistochemical study. Our case contained conventional adenocarcinomas and no signet-ring cells. Thirty two cases of mucinous adenocarcinoma of the prostate which performed on immunohistochemical study of both PSA and CEA, including our case, were reviewed. 17 of the 23 cases of immunoreactive to PSA contained conventional adenocarcinomas, and 3 of the 10 cases of immunoreactive to CEA contained them, respectively. The 6 cases of immunoreactive to CEA only contained signet-ring cells. It indicated that there seemed to be the two types of mucinous adenocarcinoma of the prostate, the one which stained positively for PSA was the subtype of conventional adenocarcinomas, and the other which stained positively for CEA and negatively for PSA was derived from the intestinal metaplasia with atypia of the prostatic urethra.

[Carcinoma of urachus: report of 15 cases and review of literature--is total cystectomy the treatment of choice for urachal carcinoma?].

PURPOSE: This study was undertaken to determine the most appropriate type of operation for the improvement of the radical cure rate and QOL of patients with urachal cancer. We assessed the association between the stage, type of operation, and prognosis of cases we experienced and those reported in Japan. PATIENTS AND METHOD: The subjects included 15 cases of urachal cancer we have experienced in the past 14 years. While clarifying the clinical patterns of these cases, the association between stage, type of operation, and prognosis was studied. Of the cases of urachal cancer reported in Japan in the recent 20 years, 75 cases in which the stage, type of operation, and prognosis were documented were selected, and the association between the stage and outcome in each type of operation was studied. RESULTS: In regard to stage, all the cases were rated as more than IIIA. As for prognosis, 9 cases (60%) are alive without cancer at the present time with a mean survival time of 7 years. Of the above patients, 3 underwent cystectomy and 6 underwent en bloc segmental resection (herein after referred to en bloc). Recurrence or cancer death was experienced in 5 patients, 2 of which were classified as stage IIIA and 3 as IIID. Of these patients, one underwent en bloc, 3 partial resection of the bladder, and one underwent exploratory laparotomy. As far as our study of the cases reported in Japan is concerned, the prognosis of the cases having undergone only partial resection of the bladder was poor, while of the cases having undergone en bloc or total cystectomy 88-100% were alive without cancer for more than 2 years if their stage was classified as IIIA or below. On the other hand, prognosis was very poor whatever the type of operation in the cases whose cancer was stage IIIC or above. CONCLUSIONS: It appears that the en bloc is most appropriate as the type of operation for the cases of urachal cancer and that the application of total cystectomy is limited to some cases. In performing the en bloc, an extensive resection of the peritoneum, resection of the posterior sheath of the rectus muscle of the abdomen, and dissection of the intrapelvic lymph nodes in addition to the conventional types of operation should be carried out positively.

[Retrospective analysis of chief complaints of patients with urogenital malignancies over the past decade at the Jikei University Hospital].

We analyzed the chief complaints of patients with four major urogenital malignancies (renal cancer, renal pelvis and ureter cancer, bladder cancer and prostatic cancer) over the past decade (1990-1999) at the Jikei University Hospital. Over the last 10 years, a high percentage of renal cancers were detected incidentally. By contrast, prostatic cancers were more likely (10.5%) than other cancers to be detected on the basis of symptoms of metastasis. However, since 1995 more prostatic cancers are being detected with prostatic-specific antigen screening at the health checkups. Gross hematuria is the chief complaint of most patients with uroepithelial cancers (cancers of the renal pelvis, ureter and bladder cancer). Additionally, renal pelvis and ureter cancers were diagnosed with screening in a few patients in the past five years.

[Clinical studies on TUR-P using clinical path: report of 50 cases and review of literature].

PURPOSE: This study was undertaken to clarify the usefulness and problems involved in the clinical path of transurethral prostatectomy (TUR-P) in hospital. PATIENTS AND METHODS: The subjects consisted of 50 patients, for whom the Department of Urology, Jikei Medical University Hospital introduced its own clinical path and performed TUR-P during a period of 9 months from July 1999 to March 2000. The mean length of hospital stay, rate of postoperative complications, and the medical insurance claims made by these patients were clarified and compared with those of 73 patients before introduction of the clinical path. RESULTS: With the introduction of the clinical path, the length of hospital stay decreased by an average of 3.4 days and the total medical insurance claims decreased by an average of 18.5%. The rate of postoperative complications before and after introduction was almost equal. CONCLUSION: Our clinical path for TUR-P was well accepted by both patients and comedicals. However, the present medical treatment system in Japan is not as yet prepared to promote the introduction of this clinical path, and it will take some time before this clinical path is introduced on a full scale.

[Decrease in anticoagulant factors in patients with prostate cancer treated with diethylstilbestrol diphosphate].

PURPOSE: Estrogen has been highly evaluated as one of the most potent endocrine agents for the treatment of prostate cancer. Unfortunately, a high risk of cardiovascular complications is a clinically important adverse effect of estrogen therapy, and occasionally the complications are fatal. In recent years a high incidence (55%) of thrombotic events has been reported in patients with congenital protein S (PS) deficiency. The aim of this study is to determine the relationship between cardiovascular complications of estrogen therapy and anticoagulant factor levels in the serum of patients with prostate cancer. MATERIALS AND METHODS: Study 1 employed 99 patients with prostate cancer: 39 were untreated, 25 were treated with LH-RH agonist therapy alone, and 35 were treated with oral diethylstilbestrol diphosphate (DESdP) 300 mg per day. We measured the serum levels of anticoagulant factors, parameters antithrombin III (ATIII), protein C (PC), PS, coagulant and fibrinolytic factors in all patients. In study 2, the adverse effects of DESdP therapy on the serum levels of anticoagulant factors were examined in 8 patients with advanced prostate cancer. RESULTS: In study 1, the ATIII and PS levels of the patients treated with estrogen therapy were significantly lower than those in either the untreated patients or the patients treated with an LHRH agonist alone. Especially, both PS antigen (51.5 +/- 16.0%) and PS activity (42.9 +/- 16.0%) were markedly lower in estrogen-treated patients than in the untreated patients (102 +/- 20.8%, 100.6 +/- 20.7%, respectively) or the patients treated with an LH-RH agonist alone (97.9 +/- 16.8%, 91.5 +/- 17.7%, respectively, both p < 0.0001). PS was decreased to below the normal lower limit of normal in 82% (24/35) of the patients on estrogen therapy. In study 2, all 8 cases showed a significant decrease in PS after DESdP therapy. CONCLUSIONS: Our results showed that the PS levels in the oral DESdP group were almost the same as in patients with congenital PS deficiency. We conclude that decreased PS may play a role in the development of cardiovascular complications in prostate cancer patients on estrogen therapy.

Mosaic-like structure of penicillin-binding protein 2 Gene (penA) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime.

Neisseria gonorrhoeae strains with reduced susceptibility to cefixime (MICs, 0.25 to 0.5 micro g/ml) were isolated from male urethritis patients in Tokyo, Japan, in 2000 and 2001. The resistance to cephems including cefixime and penicillin was transferred to a susceptible recipient, N. gonorrhoeae ATCC 19424, by transformation of the penicillin-binding protein 2 gene (penA) that had been amplified by PCR from a strain with reduced susceptibility to cefixime (MIC, 0.5 micro g/ml). The sequences of penA in the strains with reduced susceptibilities to cefixime were different from those of other susceptible isolates and did not correspond to the reported N. gonorrhoeae penA gene sequences. Some regions in the transpeptidase-encoding domain in this penA gene were similar to those in the penA genes of Neisseria perflava (N. sicca), Neisseria cinerea, Neisseria flavescens, and Neisseria meningitidis. These results showed that a mosaic-like structure in the penA gene conferred reductions in the levels of susceptibility of N. gonorrhoeae to cephems and penicillin in a manner similar to that found for N. meningitidis and Streptococcus pneumoniae.

[Fatal septic shock caused by transrectal needle biopsy of the prostate; a case report].

A 46-year-old man refer to us because of hemospermia. The prostatic gland was normal in size and consistency at rectal examination. Serum prostate specific antigen was 7.04 ng/ml. Magnetic resonance imaging showed an area of low signal intensity on T2-weighted images in the left peripheral gland, possibly indicative of carcinoma. Transrectal prostate biopsy was performed after intravenous administration of piperacillin. He developed chills and fever (39 degrees C) the next morning following biopsy. He was taken unconscious into the hospital where a diagnosis of septic shock caused by Escherichia coli was made. Five days later, he died. His general condition deteriorated notwithstanding intensive treatment. Postmortem blood cultures were positive for a piperacillin resistant Escherichia coli. Histological examination of the biopsies showed a benign prostatic hyperplasia. Autopsy showed diffuse tissue damage in the heart, lung, liver and kidneys. The prostate had numerous microabscesses. Currently, transrectal prostate biopsy is considered a generally reliable procedure to detect adenocarcinoma of the prostate. Our case seems to the sixth case report of fatal complications.

Malignant mesothelioma of testicular tunica vaginalis.

We report here a case with malignant mesothelioma of testicular tunica vaginalis. An 81-year-old Japanese man with left hydrocele was referred for operation. When hydrocelectomy was performed, a thick wall of tunica vaginalis without malignancy was observed. Seven months after hydrocelectomy, a hard irregular mass was noticed in the left scrotum, therefore inguinal orchiectomy was performed. Pathologically, the mass showed severe atypia and mitosis. The diagnosis of malignant mesothelioma was made. He refused any adjuvant treatment and died 1 year later from multiple metastases to the paraaortic lymph nodes and lumbar supine.

[Polyorchidism with undiscending testis: a case report].

We report here the 21st case of polyorchidism in Japan. A 3-year-old boy with left undiscending testis was referred to our hospital for orchiopexy. At surgery, the undiscending testis was identified as two testes. We performed left orchiopexy, because these tests had no malignancy.

[A case of lung collapse caused by endobronchial metastasis from renal cell carcinoma reinflated with laser and electrosurgical snaring].

A 62-year-old woman, who had undergone left nephrectomy for renal cell carcinoma and had received interferon-alpha for metastasis to the lung, was hospitalized because of cough, dyspnea and anorexia 16 months after nephrectomy. Chest radiography showed collapse of the right lung. We performed bronchoscopy and found a red polypoid tumor completely obstructing the right bronchus. Biopsy specimens showed clear cell carcinoma, similar to previous specimens of renal cell carcinoma. We removed the endobronchial tumor with laser and electrosurgical snaring, after which the right lung reinflated.

Ultrastructure of human pheochromocytoma cells cultured for long periods.

We conducted ultrastructural analysis of human pheochromocytoma (PC) cells maintained in primary culture for about 10 months. The cells were first isolated by the enzymatic treatment of a surgically resected tissue specimen obtained from a 37-year-old man with PC, a condition which is characterized by elevated blood levels of adrenaline and noradrenaline. It was found that noradrenaline production in the medium continued until the 90th day of culture (1330 pg/ml). The production level decreased to 20 pg/ml on the 180th day, and to 18 pg/ml on the 300th day. Examination under a transmission electron microscope (TEM) at 4 weeks of culture revealed electron-dense granules (about 200 nm in size and, presumably, rich in catecholamines), which were also observed in the tumor cells from the original PC tissue. Neurite-like processes grew at around 1 week of culture, and were still maintained at 6 months of culture. But, after 6 months of culture, the neurite-like processes contained a rosary-like elevated structure, which was suggestive of cell degeneration, as determined by a plasma polymerization replica method and observed with a scanning electron microscope. When cells were examined under the TEM, fewer electron-dense granules were observed in the cell bodies, with more numerous lipofuscin-like granules and filaments. Thus, electron-dense granules, which, presumably, contain catecholamines, were seen in a long-term culture of human PC cells. These granules decreased in number in parallel with the decrease in catecholamine levels in the culture.