Gastrointestinal stromal tumor of the rectum.

Gastrointestinal stromal tumors (GISTs) are characterized by remarkable variability in their differentiation potential, but most of these lesions do not display convincing smooth muscle or neuronal differentiation. The GISTs arising from the rectum or anal canal are extremely uncommon. We present a case of immunohistochemically proven GIST of the rectum, which was characterized by homogenous isointensity mass without necrosis or hemorrhage on T2-weighted image and by enhancement on gadolinium-enhanced study.

[Immunohistochemical study of p53 and Ki-67 overexpression in grade 3 superficial bladder tumor in relationship to tumor recurrence and prognosis].

PURPOSE: The major drawback of the current treatment for superficial bladder tumor is the high rate of recurrence. Especially, the tumor with grade 3 component has a tendency to recur and progress in stage. However, we have difficulty in predicting tumor recurrence and stage progression accurately by conventional clinicopathological factors. We evaluated the efficacy of p53 and Ki-67 overexpression as a predictor of recurrence or prognosis in patients with superficial bladder tumor of grade 3. MATERIALS AND METHODS: Samples were obtained from 41 patients with superficial transitional cell carcinoma of the bladder of grade 3 who were treated by transurethral resection (TUR). The immunohistochemical study was performed using the antibodies against the p53 protein and Ki-67 antigen on formalin-fixed, paraffinembedded tissue specimens from initial tumors. We evaluated the correlation between these results and several clinicopathological factors. RESULTS: The p53 index and the Ki-67 index in pTa, pT1a and pT1b tumors were 26.4 +/- 30.1%, 28.6 +/- 30.0%, and 34.6 +/- 32.6% (p53) and 20.5 +/- 22.5%, 20.0 +/- 29.3%, and 29.2 +/- 28.4% (Ki-67). There was no significant difference between the each index and tumor stage. Eighteen cases (43.9%) had intravesical recurrence. The p53 index of the initial tumor from the tumor free cases (n = 23), recurrent cases without stage progression (n = 12), and stage progression cases (n = 6) were 19.7 +/- 28.2%, 42.0 +/- 28.7%, and 42.5 +/- 32.0%. Between the recurrence-free cases and the recurrent cases without progression, the p53 index of the initial tumor had statistical significance (p < 0.05). The Ki-67 index was shown to be the same pattern as the p53 index, but there was not statistical significance. Four of patients with stage progression had tumor progression within six months. Three of the patients with tumors with stage progression died of the cancer. In multivariate analysis, tumor multiplicity (p = 0.01), BCG intravesical instillation (p = 0.04), p53 index (p = 0.01) and Ki-67 index (p = 0.02) were the positive risk factors for tumor recurrence, but only the p53 index was the positive risk factor for prognosis fo the patients (p = 0.03). CONCLUSION: These results suggest that the immunohistochemical study of p53 overexpression is a useful predictor for tumor recurrence and prognosis in patients with superficial bladder tumor with grade 3.

MT neurons in the macaque exhibited two types of bimodal direction tuning as predicted by a model for visual motion detection.

We previously proposed a model for detecting local image velocity on the magnocellular visual pathway (Kawakami & Okamoto (1996) Vision Research, 36, 117-147). The model detects visual motion in two stages using the hierarchical network that includes component and pattern cells in area MT. To validate the model, we predicted two types of bimodal direction tuning for MT neurons. The first type is characteristic of component cells. The tuning is bimodal when stimulated with high-speed spots, but unimodal for low-speed spots or for bars. The interval between the two peaks widens as the spot's speed increases. The second type is characteristic of pattern cells. The tuning is bimodal when stimulated with low-speed bars, but unimodal for high-speed bars or for spots. The interval widens as the bar's speed decreases. To confirm this prediction, we studied the change of direction tuning curves for moving spots and bars in area MT of macaque monkeys. Out of 35 neurons measured at various speeds, six component cells and four pattern cells revealed the predicted bimodal tunings. This result provided neurophysiological support for the validity of the model. We believe ours is the first systematic study that records the two types of bimodality in MT neurons.

High responsiveness of cytosolic free calcium concentration to angiotensin II in cultured pulmonary arterial myocytes from pulmonary hypertensive rats.

Pulmonary arterial myocytes were cultured from normotensive and pulmonary hypertensive rats. Microfluorimetry of Ca2+ signals in fluo-3-loaded single myocytes at day 7 of culture was performed by a laser-scanned confocal imaging system. The resting level of cytoplasmic Ca2+ concentration ([Ca2+]i) in vascular myocytes obtained from hypertensive rats was higher than that in cultured myocytes obtained from normotensive rats. Angiotensin II elevated [Ca2+]i in the vascular myocytes cultured from both normotensive and hypertensive rats. However, a rise of [Ca2+]i induced by angiotensin II in the vascular myocytes obtained from pulmonary hypertensive rats was higher than that obtained from normotensive rats. On the other hand, the response of [Ca2+]i to A23187 did not differ between the vascular myocytes cultured from normotensive and hypertensive rats. The present results suggest that the resting and angiotensin II-responsive levels of [Ca2+]i in pulmonary arterial myocytes cultured from pulmonary hypertensive rats are higher than those cultured from normotensive rats.

Responsiveness of cytosolic free calcium concentration in cultured rat pulmonary arterial smooth muscle cells: confocal microscopic measurement.

Rat pulmonary arterial smooth muscle cells were primarily cultured. alpha-actins in pulmonary arterial smooth muscle cells at day 7 of culture were observed by an immunofluorescence staining method using anti-alpha-actin antibody. Microfluorimetry of Ca2+ signals in fluo-3-loaded single smooth cell at day 7 of culture was performed by a laser-scanned confocal imaging system. The effects of several kinds of Ca(2+)-mobilizing drugs on cytoplasmic Ca2+ concentration ([Ca2+]i) were examined. KCl, a depolarizing agent, and norepinephrine, an alpha-adrenergic agonist, equally increased [Ca2+]i. Angiotensin II, a receptor agonist, and caffeine, a Ca(2+)-induced Ca2+ releaser, elevated [Ca2+]i in the same manner but was more potent than KCl and norepinephrine. Br-A23187, a Ca2+ ionophore, most potently increased [Ca2+]i. The present results suggest that drug receptors on plasma membrane, Ca2+ entry pathways and Ca(2+)-releasing mechanisms act normally, and that our cultured pulmonary arterial smooth muscle cells may be a good model for the study on the essential role of Ca2+ in vasoconstriction.

[Urinary neopterin levels in patients with genitourinary tract malignancies].

BACKGROUND: Neopterin is released from macrophages upon stimulation with gamma-interferon, secreted by activated T cell. Therefore it has been recognized as a useful indicator of the activation of the T cell-macrophage system. Increased neopterin levels are observed in patients with acute graft rejections, viral infections, auto-immune diseases and several malignancies. Urinary neopterin concentrations were determined in patients with genitourinary tract malignancies to evaluate the usefulness of neopterin as a tumor marker. METHODS: Urinary neopterin concentrations were determined by high-performance liquid chromatography in 90 patients with genitourinary tract malignancies and 28 patients with benign urological tumors and 34 healthy subjects. RESULTS: Increased urinary neopterin levels were observed in 52% of the patients with genitourinary tract malignancies and 7% with benign urological tumors. The positivity rate in patients with renal cell carcinoma (RCC), renal pelvic and ureteral tumor, bladder tumor (BT), prostatic carcinoma (PC) and testicular tumor was 68%, 80%, 47% and 30%, respectively. The difference in the urinary neopterin levels between low and high stages was highly significant (p < 0.0005) in patients with RCC (stage I-II vs. stage III-IV) and BT (T1S-1 VS. T2-4). The urinary neopterin levels were also correlated with the tumor grade in patients with RCC and PC. CONCLUSION: Our study suggests that urinary neopterin levels may supplement laboratory examinations for patients with genitourinary tract malignancies, providing useful information in evaluating the tumor stage and follow-up of the disease.

[Histopathological prognostic factors in 146 patients with renal cell carcinoma: comparison between incidental and non-incidental cases].

To characterize the prognostic factors among pathological structural pattern, cell type, infiltration, and incidental or non-incidental renal cell carcinoma (RCC), we reviewed the records of 146 patients with RCC who underwent nephrectomy at our institute. The patients were 26 to 86 years old (mean age 58). The men-to-women ratio was 3.2:1. The tumor originated in the right kidney in 83 patients and in the left in 63. The solid pattern was associated with poorer survival than other patterns (p < 0.01). Spindle or pleomorphic cell type had poorer survival than common type (p < 0.01). The number of incidentally discovered RCC has increased since 1986, and survival is better than in non-incidental RCC, because of smaller tumor size, low stage tumor (stages 1, 2; 83.6%), and fewer papillary or solid type. In addition, there were no spindle or pleomorphic cell type, grade 3 or INF gamma-positive case. Survival is good even when the tumor is large.

[The advantage of a thin flexible ureteroscope with a new real-time processing system].

To observe the upper urinary tract more clearly with a thin flexible endoscope, we developed a novel real-time processing system. This system enhances the parts of the dark cladding around the core by individual strong brightness of each image fiber. The upper urinary tract in eight patients was examined using a thin flexible endoscope with this system at retrograde pyelography or at urological operation. Six patients had hydronephrosis and 2 had filling defects in the renal pelvis or calyx. The endoscope was 0.75 mm in diameter and had 300 pixels of image fiber. The objective portion could be assessed successfully in seven of eight. Significantly finer and colorful image could be obtained with this system compared with the conventional method and the epithelium could be clearly observed. We conclude that this real-time processing system remarkably improves the quality of image obtained with the thin flexible ureteroscope and makes it a more promising modality in the diagnosis and treatment of the upper urinary tract.

[Immunological study of interferon-gamma therapy for advanced renal cell carcinoma].

Immunologic and anti-tumor effects of interferon-gamma were studied in six patients with advanced renal cell carcinoma. A daily dose of 10 x 10(6) JRU/m2 of interferon-gamma (IFN-gamma) was given consecutively for five days and the treatment reiterated nine days later. Then the same dose was given every two days for three times and this regimen was also reiterated nine days later. Peripheral blood lymphocytes were analyzed before and one, three, five and eight weeks after the initial administration of IFN-gamma. Although the total number of lymphocytes and monocytes were not changed, CD8 (23.4 to 31.2%, p < 0.05), CD16 (12.4 to 19.3%, p < 0.01) and LeuHLA-DR (29.0 to 39.5%, p < 0.01) positive lymphocytes were significantly increased after the therapy. Non-induced LAK activity (0.6 to 10.8%, p < 0.05) and serum neopterin (3.5 to 10.8 nmol/L, p < 0.01) were also increased. These immunological parameters drastically changed during the consecutive administration of IFN-gamma, and tended to return to the previous value after this period. However, tumor regression was not clinically obtained. Our findings indicate that interferon-gamma stimulated the anti-tumor activity of the host, and administration of IFN-gamma is thought to be of immunological significance even in the advanced high stage cases.

[Absorption of tetrahydropyranyl adriamycin administered intravesically immediately after transurethral resection of bladder carcinoma].

Absorption of tetrahydropyranyl adriamycin (THP) administered immediately after transurethral resection of bladder carcinoma (TUR-Bt) has not been reported. In this study, we have examined the absorption of THP and the systemic toxicity in the early post-TUR period. Of 21 patients with bladder carcinoma, 10 had a solitary tumor and 11 multiple tumors. Twenty mg THP in 40 ml of sterile water was intravesically administered on days 1, 3, 5, 7, 14 and 28, and then every 4th week. The THP solution was retained for 2 hours. The blood THP concentration was measured 30 minutes and 2 hours after the intravesical administration on days 1, 7 and 28. No systemic side effects were observed. Thirteen of the 38 (34%) samples contained a detectable level (more than 1 ng/ml) of THP on the post-TUR-Bt on day 1, 8, of 42 (19%) on day 7, and 3 of 18 (17%) on day 28. Altogether, 24 of the 98 (24%) samples contained more than 1 ng/ml THP. The highest blood THP level was 23 ng/ml on day 1. The differences between frequency of detection of blood THP in the samples at 30 minutes and 2 hours were not statistically significant. The difference between average concentration of blood THP of patients with solitary and multiple tumors also was not significant. These results indicate that intravesical THP administration starting within 24 hours after TUR-Bt can not result in significant systemic absorption of THP, and the systemic toxicity can be avoided.

[Serum uptake of doxorubicin intravesically administered soon after transurethral resection of bladder carcinoma].

To obtain the maximum prophylactic effect of intravesical chemotherapy on the bladder tumor recurrence treatment should be started early. Since 1983, we have been initiating prophylactic instillation of doxorubicin hydrochloride (DXR) on the first post-transurethral resection (TUR) day. This study was conducted to define serum uptake of DXR and systemic toxicity in the early post-TUR period. Fifteen TURs were carried out on 14 patients with superficial bladder carcinoma. DXR (30 mg) in normal saline (30 ml) was intravesically administered 1, 3, 5, 7 and 14 days after TUR, and every 4 weeks thereafter. DXR solution was kept in the bladder for 2 hours. The serum DXR concentration was measured 30 minutes and 2 hours after the instillation through 1 to 5 days after TUR. Intolerable vesical irritability was seen in 4 of 60 instillations. No systemic side effects, however, were observed. Three of 24 samples contained a detectable level (10 ng/ml) of DXR on the post-TUR day 1, 6 of 22 samples on the post-TUR day 3, and 6 of 14 samples on the post-TUR day 5. Overall, 15 of 60 samples contained more than 10 ng/ml DXR. The highest serum DXR level was 47 ng/ml at the post-TUR day 1. Frequency of detection and average levels of serum DXR in 30-minute and 2-hour samples were not significantly different. Average concentrations in patients with multiple or diffuse tumor and solitary tumor were also not significantly different. These results indicate that intravesical instillation starting within 24 hours after TUR does not produce significant serum uptake of DXR, and systemic toxicity can thereby be avoided.

[Chemosensitivity testing on human bladder cancer cell lines, using MTT-assay].

Sensitivity of human transitional cancer cells to anticancer agents was evaluated utilizing cultured cell lines. T-24, MGH-U1 and KU-1. Simultaneously, chemosensitivity tests combined with 42 degrees C hyperthermia were performed. Cells inoculated in 96-well multiplates for 48 hours, were exposed to graded concentrations of doxorubicin (DOX), mitomycin C (MMC), bleomycin (BLM), peplomycin (PEP), cis-diamminedichloroplatinum (II) (CDDP) for 2 to 48 hours. After additional culture for 48 hours, viable cell numbers were estimated by the dye exclusion assay (DEA) and tetrazolium-based colorimetric assay (MTT-assay). In 2-hour exposure, most of anti-cancer agents did not significantly suppress the growth of the cell lines. Only DOX suppressed the cell growth. In 6-hour and 48-hour exposure, DOX, MMC and CDDP showed significant growth inhibitory effect on the transitional cancer cell lines. The effect of BLM and PEP was insufficient. The hyperthermia of 42 degrees C enhanced the growth inhibitory effect of MMC and CDDP, but did not influence the effect of DOX. In comparison of DEA and MTT-assay, viable cell numbers measured by DEA well correlated with the optical density in MTT-assay. Since MTT-assay is a semiautomated, rapid and inexpensive assay with good reproducibility, it can be a useful substitute for DEA in chemosensitivity testing of cancer cells.