Establishment of a novel species- and tissue-specific metastasis model of human prostate cancer in humanized non-obese diabetic/severe combined immunodeficient mice engrafted with human adult lung and bone.

Bone is the most common site of metastasis in prostate cancer (PC), and to generate an animal model to investigate the basis of the unique organ tropism of PC cells for bone, we engrafted humanized non-obese diabetic/severe combined immunodeficient (NOD/SCID-hu) mice with human adult bone (HAB) and lung (HAL). Human PC cell lines LNCaP (1 x 10(7)) and PC-3 (5 x 10(6)) were injected into male NOD/SCID-hu mice via the lateral tail vein at 3-4 weeks after implantation. At 8 weeks after the injection, LNCaP and PC-3 cells had metastasized specifically to HAB in 35 and 65%, respectively, of the mice. The tumors formed by LNCaP appeared to be the osteoblastic type, whereas the PC-3 tumors consisted of osteolytic lesions without any surrounding osteogenic response. A feature of experimental metastasis of PC in NOD/SCID-hu mice was its specificity for HAB tissue. Human PC cells had no or very low metastatic potential in regard to implanted HAL, mouse bone, or native mouse bone. These findings indicate that metastasis of PC cells to HAB is both species and tissue specific. The availability of this small animal model could provide a useful tool for identifying and analyzing important features of the human PC metastatic process that cannot be addressed in conventional metastasis models.

Image analysis of microvessel surface area predicts radiosensitivity in early-stage laryngeal carcinoma treated with radiotherapy.

PURPOSE: The tissue oxygenation level, which is theoretically governed by distance from blood vessels, is one of the most important modulators of the radiosensitivity of carcinoma. A computed image analysis system for the detection of tissue oxygenation was developed to establish a method of predicting radiosensitivity in early-stage laryngeal carcinoma treated by curative radiotherapy. EXPERIMENTAL DESIGN: Microvessel structures labeled with CD31 antigen were investigated in 55 patients undergoing curative radiotherapy for T1 and T2 laryngeal carcinoma. We calculated (a) microvessel density [(MVD) vessels/field] under a microscope; (b) the ratio of the total microvessel number (TN):tumor area (TA) [TN:TA; vessels/mm2]; (c) the ratio of the total microvessel perimeter (TP):TA (TP:TA; mm/mm2); and (d) the ratio of tumor tissue area >150 microm from microvessels (hypoxic ratio; %) as parameters of tissue oxygenation in each whole biopsy specimen by using an image analyzer. We compared each of these factors with radiosensitivity. RESULTS: Mann-Whitney's U test revealed that tumors with a high MVD (median, 42 vessels/field), high TN:TA ratio (median=40.9 vessels/mm2), high TP:TA ratio (median, 2.92 mm/mm2), and low hypoxic ratio (median, 30.3%) had significantly greater radiosensitivity than tumors with a low MVD, low TN:TA ratio, low TP:TA ratio or high hypoxic ratio (P = 0.002, P = 0.0004, P < 0.0001, and P = 0.004, respectively). CONCLUSIONS: Prediction of radiosensitivity on the basis of the TP:TA ratio can be used as an efficient means of avoiding ineffective radiation, complications after salvage surgery, and prolonged hospital stays.

Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy.

Curative radiotherapy is the first choice of therapy for T1 and T2 stage laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation. Patients with recurrent tumors who undergo salvage surgery require prolonged nasal feeding. Therefore, clinical interest has been focused on elucidating a predictive factor indicating which tumors are likely to be radiosensitive before radiotherapy. We analyzed the relations between radiosensitivity and clinicopathological factors (gender, tumor location, histological factors, and clinical tumor-node-metastasis stage), expression of apoptosis-related proteins (p53, bax, bcl-2), apoptotic index using the terminal deoxynucleotidyltransferase-mediated nick end labeling method, expression of cell proliferation-related proteins (Ki-67-labeling index and epidermal growth factor receptor overexpression) and microvessel density (MVD, vessels/field = 0.391 mm2) in biopsy specimens from 31 LSCC patients given radiotherapy (total radiotherapy dose of 52-70 Gy over 4-6.5 weeks). Univariate analysis revealed that tumors with a high MVD (> or =35 vessels/field) showed better radiosensitivity than those with a low MVD (<35 vessels/field, P = 0.008) and that a high Ki-67-labeling index (> or =40%) was weakly associated with radiosensitivity (P = 0.056). Multivariate analysis and Kaplan-Meier analysis showed that MVD alone had significant predictive power for radiosensitivity in T1 and T2 stage LSCCs after radiotherapy (P = 0.012, 0.0003, respectively). No significant association between clinicopathological factors, or of overexpression of p53, bax, bcl-2, epidermal growth factor receptor, or apoptotic index, with radiosensitivity was found. These results indicate that MVD is a potentially useful clinical factor predicting radiosensitivity for patients with early stage LSCCs before treatment.

[Transurethral resection of the prostate for patients with dementia].

During the period from July 1995 to June 1996 we performed transurethral resection of the prostate (TURP) on 824 patients with benign prostatic hyperplasia (BPH). Among them, 13 were dementia patients between 74 and 96 years old; they presented with urinary hesitancy in 6, retention in 4, frequency in 2 and incontinence in 1 patient. Past history included stroke in 7, hypertension in 6, pulmonary tuberculosis in 4, diabetes in 3, asthma in 2, angina pectoris in 1, Parkinson's disease in 1, pneumonia in 1, and hepatitis in 1. Careful preoperative examination revealed that they were proper candidates for TURP. They underwent TURP under spinal anesthesia. The mean operative time was 34 min, ranging from 20 to 60 min. The adenoma resected weighed 24 g on the average, ranging from 7.5 to 48 g. During surgery, although hypotension was noted in 2 patients, there was no serious morbidity. Their mental condition was well controlled with ketamine and diazepam during and after surgery. Postoperative complications included acute myocardial infarction in 1, multiple gastric ulcer in 1, and decubitus in 1. None died within 3 months after TURP, 3 died there after, and 10 patients were alive at the mean follow-up period of 26 months. Six patients reported good urination, 3 reported some improvement in urination after surgery, although requiring intermittent catheterization and 1 developed mild incontinence. In conclusion, TURP appears to provide some benefit in selected patients with dementia and should not be considered to be a contraindication for such patients.

Compensatory renal hypertrophy and changes of renal function following nephrectomy.

We studied the changes in the serum creatinine level and the volume of the remaining kidney following nephrectomy using contrast-enhanced compounded tomogram (CT) scans. Twenty-five patients undergoing nephrectomy for renal cell carcinoma without obvious disease in the remaining kidney were carefully followed for a period of at least two years at our hospital. Twelve patients received follow-up CT scans each year after nephrectomy. The ellipsoid volume of the kidney was calculated by measuring the 3-dimensional size on CT scans. The mean relative volume (%) of the remaining kidney increased up to year 3 postoperatively, and the final mean relative volume at varying periods from years 2 to 7 was 120%. Kidneys that were smaller prior to nephrectomy showed a tendency to have a larger final relative volume after nephrectomy, although there was no significant correlation between the kidney volume prior to nephrectomy and at final measurement. The mean serum creatinine level was significantly increased at one year after nephrectomy, but it decreased significantly over time. Therefore, both compensatory renal hypertrophy and improved renal function seemed to be established within several years after nephrectomy. However, the improvement of serum creatinine was delayed compared with the increase of kidney volume. That is, renal plasma flow might be increased early by compensatory renal hypertrophy, followed within a few years by an increase in glomerular filtration and a decrease of serum creatinine.

[Retroperitoneal schwannoma arising from the adrenal area: a case report].

A 67-year-old woman presented with upper abdominal pain and was found to have a suprarenal tumor by ultrasonography and CT scanning. Under a diagnosis of non-functioning adrenal tumor, we made an extraperitoneal approach via a lumbar incision and removed the tumor together with the left adrenal gland. There was minimal blood loss. The resected tumor was firm and had a yellowish-white cut surface. The lesion measured 60 x 40 x 35 mm and weighed 50 g. The pathological diagnosis was benign schwannoma, mainly of the Antoni type A. This is the 27th case of benign schwannoma in the adrenal area reported in the Japanese literature.

[Renal transplantation for patients with systemic lupus erythematosus: report of two cases].

Renal transplantation for patients with systemic lupus erythematosus (SLE) remains controversial. We performed living-tissue related renal transplantation on a 45-year-old woman with SLE and an eight-month history of hemodialysis. We also did cadaveric renal transplantation on a 41-year-old man with SLE and a 12-year history of hemodialysis. Serological tests including tests for antinuclear antibodies and complements were negative prior to surgery and throughout the course in both cases. The latter patients survived herpes-zoster virus infection in month 6 and bacterial pneumonia in month 9 after transplantation. Neither patient experienced any rejection or relapse of lupus nephritis after the procedure, and both maintained good renal allograft functions. The recurrence of lupus nephritis is reportedly extremely rare, i.e., with a possibility rate of less than 1% in transplant patients with burnt-out SLE. To the best of our knowledge, these cases are the 27th and 28th case reports of renal transplantation for SLE patients in Japanese literature.

[Giant prostatic hypertrophy: a case report].

Benign prostate hypertrophy weighing more than 200 g is defined as giant prostatic hypertrophy. An 81-year-old man presented with urinary retention and underwent retropubic prostatectomy. Blood loss was 1,850 ml and he received 800 ml of autologous blood. The removed specimen weighed 267 g and pathology revealed benign hyperplasia of the prostate. We collected 32 such cases from the Japanese literature.

Retroperitoneoscopic heminephrectomy of the right upper collecting system emptying into an ectopic ureterocele in a 5-year-old girl: a case report.

A 5-year-old girl with a history of recurrent urinary tract infection since the age of 14 months was diagnosed as having a right duplicated urinary collecting system with the upper ureter ectopically opening in the urethra. She underwent retroperitoneoscopic heminephrectomy for a right dysplastic kidney and open ureterocelectomy and reimplantation of the refluxing lower ureter via Pfannenstiel incision. She survived the procedure without serious complications and resumed normal daily activities by day 6. To the best of our knowledge, this case is the 16th case of laparoscopic heminephrectomy for pediatric patients and the first case treated by the retroperitoneal approach in the English literature.

[Cadaveric renal transplantation for Goodpasture's syndrome: a case report].

A 19-year-old man with a history of histologically-proven Goodpasture's syndrome (hemoptysis, rapidly progressive glomerulonephritis, and positive anti-glomerular basement membrane (anti-GBM) antibody) was maintained on hemodialysis for 21 months. After steroid pulse therapy and plasmapheresis, his anti-GBM antibody disappeared. His stable condition on dialysis and a session of plasmapheresis prior to surgery allowed him to undergo cadaveric renal transplantation from a 34-year-old man. The blood type was identical (group A and Rh (+)), and there was 1 and 0 mismatch of HLA class 1 and 2, respectively. The initial immunosuppressants included cyclosporine, methylprednisolone, mizoribine, azathioprine, and anti-lymphocyte globulin (ALG). The transplanted kidney regained function on day 6 and he was free from hemodialysis. Circulating anti-GBM antibody was negative after surgery. The graft has functioned well for almost 4 years after transplantation without any episodes of renal or pulmonary complications. To the best of our knowledge, this is the first report of renal transplantation for Goodpasture's syndrome in the Japanese literature.

Robotic-assisted laparoscopic radical prostatectomy: initial 15 cases in Japan.

Recently, we have introduced robotic-assisted laparoscopic radical prostatectomy (RALP) in Japan. This article describes the details of a training program to shorten the learning curve in the absence of an urologist with expertise in robotic surgery. Five months after a 2-day training course of robotic surgery, RALP was first performed in Japan, and a total of 15 cases were performed in the subsequent 4 months. Our training program consisted of: (1) image training using surgical operation videos, (2) dry lab training using a sham pelvic cavity model, and (3) intraoperative mentoring. The operative procedure was divided into five consecutive stages, and time required to complete each stage was recorded. Robotic radical prostatectomy was completed in all patients without conversion to open surgery, except for the first patient in whom a restriction to a 2-h operation had been imposed by the ethics committee. The mean console time and the mean intraoperative blood loss (including urine) reduced from 264.2 min and 459.4 ml, respectively, in the first 11 cases, to 151 min and 133.3 ml, respectively, in the last three cases. With direct intraoperative guidance by the mentor during cases 13 and 14, the operation time was reduced at all five stages of the operative procedure. Our training program proved remarkably effective in reducing the learning curve of RALP in Japan, where there is no person with expertise in robotic surgery.

Vitamin B6 deficiency augments endogenous oxalogenesis after intravenous L-hydroxyproline loading in rats.

The effects of an intravenous hydroxyproline load on endogenous oxalogenesis were compared in rats fed a standard diet or a vitamin B6-deficient diet. Twelve male Wistar rats were randomized to two groups and were fed either a standard diet (control group) or a vitamin B6-deficient diet for 3 weeks. Then the animals were intravenously administered 100 mg (762.6 micromol)/ml hydroxyproline. In the control group, infusion of hydroxyproline increased the 5-h urinary oxalate and glycolate excretion above baseline to 0.27% (2.02 +/- 1.11 micromol) and 0.32% (2.43 +/- 1.60 micromol) of the administered dose (mol/mol), while it was respectively 2.01% (15.24 +/- 2.13 micromol) and 0.00% (-0.02 +/- 0.19 micromol) of the dose in the vitamin B6-deficient group. Therefore, vitamin B6 deficiency augmented endogenous synthesis of oxalate from hydroxyproline by 7.56-fold (15.24/2.02) compared with that in the control group. Urinary citrate excretion was significantly lower at baseline and all other times in the vitamin B6-deficient group compared with the control group. In conclusions, L-hydroxyproline loading augmented endogenous oxalogenesis in the vitamin B6-deficient group without causing hyperglycolic aciduria, and also led to significant hypocitraturia. These findings suggest that hydroxyproline is not metabolized to oxalate via glycolate, but rather via the 4-hydroxyglutamate to glyoxylate pathway (usually requiring vitamin B6-dependent enzymes) even in the presence of vitamin B6 deficiency.

Transitional cell carcinoma of the renal pelvis forming tumor thrombus in the vena cava.

A 47-year-old man presented with a left renal incidentaloma without hematuria. The tumor was complicated by inferior vena cava (IVC) thrombus extending from Th11 to L4. A temporary IVC filter was introduced prior to surgery. A midline incision was used to perform a left radical nephrectomy and en bloc lymphadenectomy with excision of the inferior vena cava from above the level of the left renal vein to 2.5 cm above the confluence of the common iliac veins. The pathological diagnosis was invasive transitional cell carcinoma. The tumor thrombus consisted of transitional cell carcinoma that histologically invaded the walls of the IVC. He died of cancer 17 months after the operation for the liver metastases. This is the 18th case report of such a presentation in the literature.

Prostate-specific antigen induces osteoplastic changes by an autonomous mechanism.

The high prevalence of osteoplastic bone metastasis in prostate cancer (PC) is believed to be attributable to the production of osteoblast-stimulating factors by PC cells. Prostate-specific antigen (PSA) is a serine protease and an important serological marker for PC. Exposure of osteoblasts to PSA in vitro was found to result in cell proliferation and marked upregulation of transforming growth factor-beta (TGF-beta) mRNA expression. This PSA-induced increase in osteoblast proliferation was inhibited by anti-TGF-beta antibodies and serine protease inhibitors. In vivo, PSA markedly enhanced osteoplastic changes in human adult bone implanted into NOD/SCID mice without PC cells, and alpha(1)-antichymotrypsin prevented the PSA-induced increase in bone volume. PSA promotes osteoplastic change by activating an osteoblast autonomous mechanism that is independent of the production of bone growth factors by PC cells.