Efficacy of S-1 in patients with castration-resistant prostate cancer: a phase II study.

OBJECTIVES: This study was conducted to evaluate the efficacy and safety of S-1, an oral fluoropyrimidine derivative, in Japanese patients with castration-resistant prostate cancer (CRPC). The primary endpoint was prostate-specific antigen (PSA) response. METHODS: In this open-label phase II study, S-1 was started at a dose of 80, 100 or 120 mg daily based on body surface area (BSA) for 28 days, followed by 14 days of rest. Patients with histological proof of prostate cancer refractory to hormonal therapies were eligible. Patients who received prior chemotherapy were excluded. All patients provided written informed consent. To observe 20% confirmed PSA response, 33 assessable patients were needed. Treatment was continued until disease progression or the development of intolerable toxicity. RESULTS: A total of 35 eligible patients were enrolled. The median number of treatment cycles was 3. PSA response was observed in 8 patients (22.9%, 90% CI 11.9-37.5), including 3 in which (8.6%) the PSA level normalized. The median overall survival was 25.4 months. The most common treatment-related grade 3 toxicity was anorexia (14.3%). There was no death during the study. CONCLUSION: S-1 monotherapy is active against castration-resistant prostate cancer and has acceptable toxicity.

[One-week effects of Tamsulosin on benign prostatic hyperplasia assessed with a daily symptom score].

The early effects of Tamsulosin within one week of administration on lower urinary tract symptoms in patients with benign prostatic hyperplasia (BPH) were investigated. Patients with newly diagnosed BPH were randomized into a Tamsulosin group and a Eviprostat group. Changes in subjective symptoms daily for 7 days after the start of administration and in the 4th week (8 times in total) were evaluated using seven symptoms in the International Prostate Symptom Score (IPSS) and the quality of life (QOL) index entered in a self-scoring diary kept by the patients daily. In the Tamsulosin group, the IPSS total score showed significant improvements. Significant improvements were observed in the incomplete emptying and frequency scores from the day after the start of administration, in the intermittence and straining scores from day 2, in the urgency and weak stream scores from day 3 and in the nocturia score from day 5. The QOL index significantly improved on day 7. In comparison with Eviprostat, Tamsulosin showed a stronger improvement tendency in the total IPSS, voiding symptoms score and incomplete emptying score and the difference was significant. The difference between the two groups was especially marked for the intermittence and weak stream scores and Tamsulosin showed significantly better early effects. Tamsulosin also showed significantly better early effects than Eviprostat in the QOL index. In conclusion, it was clear that Tamsulosin caused significant improvement in lower urinary tract symptoms associated with BPH as a whole from a very early stage within one week after administration.

[A comparative study assessing clinical effects of naftopidil and tamsulosin hydrochloride on benign prostatic hyperplasia with overactive bladder].

PURPOSE: We compared the efficacy of naftopidil with that of tamsulosin hydrochloride for 154 symptomatic benign prostatic hyperplasia (BPH) patients who also suffered from overactive bladder (OAB) symptoms. MATERIALS AND METHODS: Naftopidil and tamsulosin hydrochloride were administered for eight weeks. The international prostate symptom score (IPSS), QOL index, maximum flow rate (Q(max)), residual urine volume (RUV) and side effect profile were determined before the administration and after eight weeks of treatment. RESULTS: In the naftopidil group, seven parameters of IPSS and QOL index were improved significantly at the endpoint compared to the baseline. In the tamsulosin group, all parameters except frequency and straining were also improved. Both drugs improved the Q(max) at the endpoint, too. The RUV did not change in both groups. Naftopidil was also superior to tamsulosin hydrochloride regarding general treatment outcome by the Japanese clinical guideline of urinary disturbance. CONCLUSIONS: This study demonstrated that naftopidil was clinically efficacious in the treatment of BPH patients with OAB.

A case of ganglioneuroma in which 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol scintigraphy showed high uptake in the adrenal gland leading to a misdiagnosis.

We experienced a case in which 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol (131I-adosterol) scintigraphy showed high uptake in the right adrenal gland. We diagnosed functional cortical adenoma because of the finding of 131I-adosterol scintigraphy. However, no positive findings for the existence of cortical adenoma were obtained in other examinations and we performed right adrenalectomy. Unexpectedly, pathological finding showed the right adrenal gland was occupied with a large ganglioneuroma. This is an instructive case in which 131I-adosterol scintigraphy showed abnormal high uptake in the adrenal gland, in spite of the fact that the adrenal gland was occupied by a tumor derived from adrenal medulla.

Metastasis to the orbit from transitional cell carcinoma of the bladder.

PURPOSE: To demonstrate the pathological features of the extremely rare metastatic transitional cell carcinoma (TCC) from the bladder to the orbit, and to review the literature on metastatic TCC to the orbit. METHODS: A 74-year-old man experienced 2 weeks of red eye, proptosis, diplopia, pain, and visual loss in the right eye. Three years previous to the current presentation, the patient had undergone a transurethral resection for superficial and moderately differentiated TCC of the bladder. A transseptal anterior orbitotomy was performed. RESULTS: Histopathological examination of the orbital lesion revealed nests of carcinomatous cells. Atypical pleomorphic cells with vacuolated cytoplasm were evident. The cellular morphology of the orbital lesion was identical to that of the primary TCC. There have been 12 previously reported cases of metastases to the orbit from TCC of the bladder, with the time from onset of primary TCC to observation of ocular symptoms ranging from 3 weeks to 11 years. Mean survival after orbital metastasis developed from TCC was 3.0 months. CONCLUSION: This study presents a detailed description of the pathological features of metastatic TCC in the orbit. In cases of orbital metastasis from TCC, patient prognosis is very poor.

[Simultaneous renal cell carcinoma and urothelial carcinoma in ipsilateral kidney, report of two cases].

Two cases of simultaneously developed renal tumors (renal cell carcinoma and renal pelvic urothelial carcinoma) in the ipsilateral kidney are reported. These underwent radical surgery under the diagnosis of renal cell carcinoma or renal pelvic urothelial carcinoma, respectively. The risk of incorrect preoperative diagnosis is discussed in terms of insufficient surgical margins. The liberal use of frozen section diagnosis and more radical resection if applicable may be the key to solve such dilemmas.

[A case of pheochromocytoma associated with incidental multiple renal cell carcinoma originating from acquired cystic disease of the kidney in hemodialysis].

The patient was a 52-year-old woman maintained on peritoneal dialysis for 9 years and on hemodialysis for 7 years. This patient complained of palpitations and hypertensive attack during the hemodialysis. Computed tomography and magnetic resonance imaging demonstrated the presence of right adrenal tumor(1.5 x 1.5 cm) and bilateral multiple renal cysts. Right adrenal pheochromocytoma was confirmed by elevated serum level of catecholamines and diagnosed by 131I-MIBG scintigram. This patient underwent right adrenalectomy and nephrectomy in consideration of future generation of cancer in the acquired cystic kidney. Histological examination confirmed malignant pheochromocytoma and small multiple renal cell carcinomas. The patient was alive without any recurrence 6 months postoperatively. To our knowledge, this is the fifth case of adrenal pheochromocytoma and renal cell carcinoma associated ACDK in a hemodialysis patient in the Japanese literature.

[Primary, nonviral, hepatocellular carcinoma in patients with prostate cancer treated by hormone therapy: 2 case reports].

We studied two cases of primary, hepatocellular carcinoma (HCC) that occurred following hormone therapy (estrogen therapy in one case and total androgen blockade therapy in another) for stage D2 prostate cancer. Prostate cancer is considered to be hormone-dependent, and androgens appear to be important hormonal factors. However, hepatocellular carcinoma has been shown to have both estrogen and androgen receptors, suggesting that this may be dependent on estrogen or androgen. Reported here are two unique cases of hepatocellular carcinoma in patients with prostate cancer; the pathogenesis of HCC in these patients was suspected to be related to diethylstilbestrol (DES) therapy and antiandrogen therapy for their prostate cancer.

[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.

A new organic superconductor, beta-(BDA-TTP)2GaCl4 [BDA-TTP = 2,5-(1,3-dithian-2-ylidene)-1,3,4,6-tetrathiapentalene].

The preparation, crystal structure and physical properties of beta-(BDA-TTP)2GaCl4 has been investigated; the salt exhibits superconductivity at 3.1 K (onset) under a hydrostatic pressure of 7.6 kbar.

2-(1,3-Dithiolan-2-ylidene)-5-(1,3-dithian-2-ylidene)-1,3,4,6- tetrathiapentalene(DHDA-TTP), a hybrid of BDH-TTP and BDA-TTP, and its metallic cation-radical salts.

The synthesis and electrochemical properties of the DHDA-TTP donor, a hybrid of 2,5-bis(1,3-dithiolan-2-ylidene)-1,3,4,6-tetrathiapentalene (BDH-TTP) and 2,5-bis(1,3-dithian-2-ylidene)-1,3,4,6-tetrathiapentalene (BDA-TTP), has been investigated, and its ability to form metallic cation-radical salts is elucidated.

A new organic superconductor, (DODHT)2BF4 x H2O.

In addition to two organic superconductors (DODHT)2X [DODHT = (1,4-dioxane-2,3-diyldithio)dihydrotetrathiafulvalene; X = PF6 and AsF6] previously reported by us, the BF4 salt of DODHT containing one water molecule [(DODHT)2BF4 x H2O] has been found to undergo a superconducting transition at 3.2 K under a hydrostatic pressure of 15.5 kbar.

Facile Dehydrogenation of alpha-Amino Acids Chelated to a Ruthenium(II) Ion: (alpha-Imino acidato)ruthenium(II) Complexes.

(alpha-Imino acidato)ruthenium(II) complexes, [Ru(II){N(R(1))=C(R(2))CO(2)}L(2)](+) (R(1) = R(2) = Me or R(1) = R(2) = -(CH(2))(3)-; L = 2,2'-bipyridine (=bpy) or 1,10-phenanthroline (=phen)), were obtained by anodic oxidation at a constant potential of the corresponding (alpha-amino acidato)ruthenium(II) complexes, N-methylalaninato or prolinato complexes, in good to excellent yields. (alpha-Imino acidato)ruthenium(II) complexes are stable in neutral or acidic aqueous solution. The half-wave potentials of alpha-imino acidato complexes are 0.73-0.78 V (vs SCE), which are more positive than those of the corresponding alpha-amino acidato complexes, 0.55-0.59 V. The crystal structure of [Ru(pro-H(2))(bpy)(2)]ClO(4).3H(2)O (pro-H(2) = 1,2-didehydroprolinato) has been determined by single-crystal X-ray analysis. Crystallographic data: space group C2/c, a = 21.73(1) Å, b = 19.33(1) Å, c = 14.58(1) Å, beta = 114.91(5) degrees, Z = 8, R = 0.0352. The length of the C=N double bond of the alpha-imino acidate moiety is 1.294(5) Å, and Ru-N(imino nitrogen) = 2.042(3) Å. The chelate ring of the alpha-imino acidato ligand is planar.

[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.

[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.

[A case of complete self-mutilation of penis].

Self-mutilation of the penis is extremely rare. A 69-year-old man was admitted after having amputated his own penis completely from its root. He had no history of psychiatric illness, but his physical condition on admission was abnormal. We performed urethrocutaneostomy, rather than replantation of the penis, because of the danger that he would reinjure himself. The patient was treated by a psychiatrist under a diagnosis of alcoholic dementia. To our knowledge, this is the 24th case of self-mutilation of the penis reported in the Japanese literature.

[Malignant fibrous histiocytoma of perirenal tissue: a case report].

A 75-year-old woman was admitted to our hospital with an extremely large retroperitoneal tumor that had been detected with ultrasound on a routine health check. She had no complaint except lumbar pain. Computed tomography revealed a heterogenous tumor located outside the right kidney which was enhanced gradually. Doppler ultrasound showed mild vascularity in the tumor. We performed tumorectomy and right nephrectomy because the tumor was adherent to the right kidney. The tumor was 16 x 11 x 7 cm in size and weighed 621 g. The histopathological diagnosis was malignant fibrous histiocytoma. The tumor was considered to have arisen from perirenal tissue.

[Prostatic cancer in a young adult: a report of 2 cases].

Patients younger than 45 years with prostate cancer are rare. Between 1999 and 2002, we studied two cases of prostate cancer in men aged under 45 years. Case 1; a 45-year-old man admitted with the chief complaint of urination disorder. Serum level of prostate-specific antigen (PSA) was 5,000 ng/ml or higher. Transrectal needle biopsy of the prostate revealed moderately differentiated adenocarcinoma. Computed tomography (CT) and bone scan showed para-aorta lymph node metastasis and bone metastasis. Hormone therapy was performed. Case 2; a 37-year-old man admitted with the chief complaint of pollakisuria and sense of residual urine. Serum level of prostate-specific antigen (PSA) was 24 ng/ml. Magnetic resonance imaging (MRI) showed that the prostate tumor invaded the bladder wall. Transrectal needle biopsy revealed poorly differentiated adenocarcinoma. Hormone therapy and radiation therapy were performed. Twenty-one cases reported in Japan in addition to the present cases are reviewed.

[Schwannoma with purely cystic form originating from the adrenal area: a case report].

A 62-year-old woman was hospitalized with complaints of right upper abdominal discomfort. Various imaging studies showed an extremely large suprarenal mass with solitary cystic formation. Partial adrenalectomy was successfully performed through the transperitoneal approach. The resected mass measured 12 x 10 x 10 cm and weighed 600 g. A pathological examination showed an Antoni-B predominant-type benign schwannoma containing a large volume of degenerative fluid. Our search of literature yielded few reports of solitary cystic schwannomas in the retroperitoneal cavity or throughout the body. This unusual cystic manifestation is thought to be a terminal stage of degeneration of a long-standing schwannoma.

[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.