Analysis of Histological Heterogeneity in Renal Cell Carcinoma: Tumor Size-Related Histological Change and its Prognostic Significance

Background: It is well recognized that the histology of renal cell carcinoma (RCC) is often heterogenous. It is also believed that the prognosis of patients with large tumors is generally poorer than those with small tumors. However, there has been no detailed study on changes in histological features of RCCs associated with tumor growth. This study was conducted to investigate whether there are any specific histological changes related to tumor size and to study the prognostic value of histological parameters in RCCs. Methods: The presence or absence of each histological component (3 cell types and 5 histological architectures) was investigated in 110 RCCs. The tumor size-associated changes in the histological composition of the RCCs were evaluated, and the prognostic significance of the histological parameters was analyzed using univariate and multivariate analysis. Results: The percentage of RCCs with multiple cell types increased with tumor size, whereas increases in multiplicity were not as prominent in the histological architectures. Several characteristic changes, however, were observed in both cell types and architectures. RCCs with a pure clear cell, pure alveolar pattern or cystic architectural pattern decreased, while those with granular or spindle/pleomorphic cell types, or papillary or solid architectural patterns increased with tumor size. A univariate analysis revealed that a clear cell type and an alveolar or cystic architectural pattern were associated with a better prognosis, while spindle/pleomorphic cells and a solid architecture pattern correlated with a poorer prognosis. Multivariate analysis of cell types and architectures showed, however, that only the presence of spindle/pleomorphic cell types and a solid architecture were independent prognostic variables. Conclusion: The histological composition of RCCs varied according to the size of the tumor. Sarcoma-tous components increased with tumor size and were independently associated with a poor prognosis. Further study is warranted to correlate specific genetic alterations with tumor growth-related histo-logical changes in RCCs.     

Enkephalin-immunoreactive fastigial neurons in the rat cerebellum project to upper cervical cord segments

By using enkephalin immunohistochemisal combined with retrograde fluorescent labelling, a great majority of neurons in the rat cerebellum sending their axons to the spinal cord were shown to contain enkephalin immunoreactivity. These neurons were numerous and clustered in the fastigialnucleus but far less abundant in other cerebellar nuclei. Enkephalin-immunoreactive fibers present in the ventral horn and the central cervical nucleus of upper cervical cord segments almost completely disappeared contralaterally following kainic acid-induced cell loss in the fastigial nucleus. The results indicate that fastigial and some other cerebellar nucleus neurons provide enkephalin-containing projections toward these spinal sites.     

Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women.

In order to investigate whether vaginal rings delivering estradiol and progesterone could prevent endometrial hyperplasia and relieve climacteric symptoms, two variants of rings were used in 20 postmenopausal women with intact uteri for 4 months. One ring designated as PI-002 (n = 8) delivered in vitro estradiol 160 microg/day and progesterone 20 mg/day, while the other (PI-003; n = 12) delivered the same dosage of estradiol but only half the progesterone (10 mg/day). Serum estrone, estradiol and progesterone were measured at pretreatment, weekly for 4 weeks, and then monthly for 4 months. The incidence of hot flushes, frequency of night sweats, mood scores, vaginal discharge and bleeding profiles were recorded. Endometrial thickness was monitored by ultrasonography. The mean estrone level was 50 pg/ml for 16 weeks. The mean serum estradiol level was 75 pg/ml for the first 4 weeks and gradually decreased to 50 pg/ml at 16 weeks. The mean progesterone level with the PI-002 ring was 5 ng/ml for the first 4 weeks and decreased to 3.5 ng/ml at 16 weeks. With the PI-003 ring, the mean progesterone level was initially 3.5 ng/ml and then decreased to 2.5 ng/ml thereafter. Significant decreases in the incidence of hot flushes and night sweats as well as a striking improvement in mood scores were noted as early as 2 weeks after insertion. Three of the 20 women discontinued the treatment, owing to ring expulsion. Increased vaginal discharge was observed with both rings in the first 6 weeks. Vaginal bleeding was more frequently apparent among users of the PI-002 ring, although bleeding and spotting were confined to the first 6 weeks. Ultrasonographic monitoring of the endometrium constantly revealed a thickness of < 3 mm for both variants throughout use for 16 weeks. An estradiol/progesterone-releasing vaginal ring is a potential alternative to long-term hormone replacement therapy with minimum attention required. It provides effective protection against endometrial hyperplasia.     

Ulnocarpal impaction syndrome restricts even midcarpal range of motion.

Ulnocarpal impaction syndrome is believed to be caused by abutment between the ulna and the ulnar carpus. We measured radiocarpal and midcarpal ranges of motion in 40 patients with ulnocarpal impaction syndrome by radiographic motion studies. The results showed that the radiocarpal and midcarpal ranges of motion were equally restricted in the affected wrist compared with the unaffected wrist. Therefore, motion of the radiocarpal joint and midcarpal joint contributed equally to total wrist motion bilaterally. No correlation between ulnar variance and the contribution of radiocarpal motion to overall wrist motion was found. Restriction of wrist motion in ulnocarpal impaction syndrome is not caused directly by abutment between the ulna and ulnar carpus, but a satisfactory explanation for restricted motion is still lacking.     

Alumina ceramic prostheses for bone tumor surgery

Summary Between 1979 and 1990 reconstruction using a ceramic prosthesis with a polycrystal alumina segment and a monocrystal alumina stem was carried out in 65 patients after the resection of malignant or benign aggressive bone tumors. Resection of 18 osteosarcomas, 5 chondrosarcomas, 9 other sarcomas, 10 giant cell tumors, 20 metastatic bone tumors, and 3 other bone tumors was followed by replacement of 17 proximal femurs, 12 distal femurs, 12 proximal tibia, 11 proximal humeri, 3 distal radii, 5 midshafts of the long bone, 2 pelvises, and 3 other parts. Results were rated excellent in 4 cases, good in 43, fair in 13, and poor in 4. In the cases with benignly aggressive or low-grade malignant tumors and those with tumors of the proximal femur, proximal tibia, or midshaft, satisfactory results can be obtained. Four skin ulcers, three dislocations, three loosenings, two infections, and two breaks were noted. Close interfacing between the ceramic prosthesis and the bone was observed radiologically in all cases with cementless fixation except in cases with high-grade malignancies in the knee joint. These results demonstrate that the ceramic prosthesis can be beneficial for the management of patients with benignly aggressive or low-grade malignant bone tumors who have retained adequate muscle strength around the joint even after tumor resection.     

Complement activation pathways associated with islet cell surface antibody (ICSA) derived from child patients with insulin-dependent diabetes mellitus (IDDM)

We studied the pathways of complement activation associated with the islet cell surface antibody (ICSA) obtained from sera of 7 patients (age less than 15 years) with insulin dependent diabetes mellitus (IDDM). The target cells were 51CR labelled rat islet cells and the complement source was human AB serum. Complement-dependent antibody mediated cytotoxicity (CAMC activity) was obtained using the percentage of cytotoxicity. CAMC activity of untreated sera was significantly inhibited by treating with EGTA or EDTA (p less than 0.001). The CAMC activity of EDTA-treated sera was significantly lower than that of EGTA-treated sera (p less than 0.001). In the inactivated human AB serum, it was lower than that of EGTA-treated sera (p less than 0.05), but not different from that of EDTA-treated sera. These results show that the complement activation associated with ICSA in patients occurred not only via the classical pathway but also via the alternative pathway.     

Prognostic significance of argyrophilic nucleolar organizer staining in soft-tissue sarcomas.

The utility of argyrophilic stain for nucleolar organizer region (AgNOR) for estimating proliferative activity and prognosis of soft-tissue sarcomas (STS) was examined. Formalin-fixed and paraffin-embedded sections of 38 cases with STS were used; the reaction product of AgNOR stain was observed as dots mainly in the nucleoli. The mean number of AgNOR dots per nucleus of tumor cells was calculated in 200 cells (AgNOR count). The AgNOR count, ranging from 1.4 to 16.1 (mean, 7.5), showed a good correlation with cellularity (r = 0.483, p less than 0.003) and histologic grade (r = 0.626, p less than 0.00005), but less shown with mitotic counts (r = 0.350, p less than 0.04). The prognosis of cases with AgNOR low-count group (5-year survival rate was 74.6%) was much better than those in high count group (33.3%) (p less than 0.0005). The AgNOR count correlated well with reactivity of tumor cells for Ki-67 staining, which was available only in freshly prepared sections. These findings suggested that the AgNOR staining is a simple and useful method for estimating tumor-cell proliferation and prognosis of patients with STS.     

Influence of age and severity of hypertension on blood pressure response to isometric handgrip exercise.

The influence of age and severity of hypertension on the blood pressure response to isometric handgrip exercise (IHG) was studied in essential hypertensive patients (n = 122). The change in blood pressure during IHG in elderly patients with isolated systolic hypertension (ISH) (n = 12) was also studied. Left ventricular hypertrophy due to hypertension was used as an index of the severity of hypertension. The change in systolic blood pressure (SBP) during IHG was markedly greater in essential hypertensives than in normotensive subjects (n = 36). Among hypertensive patients, the change in SBP increased with increasing severity of hypertension. This change in SBP was not influenced by age. The change in SBP during IHG in patients with ISH was significantly smaller than that in essential hypertensive patients and was similar to that in normotensive subjects in the elderly. These results demonstrate that age does not affect the increased blood pressure response to IHG in essential hypertensive patients but the greater the severity of hypertension, the greater the increase in SBP during IHG. Elderly patients with ISH do not have an enhanced blood pressure response to IHG.     

Syntheses and antifungal activities of 1-[4-phenyl-2-(phenylthio or acyloxy)-n-butyl]-1H-imidazole derivatives]

The title compounds (4b, d-f, h-j) were prepared from 1-[4-(p-substituted phenyl)-2-chloro-n-butyl]-1H-imidazoles and the corresponding thiophenols or mercaptopyridines. Acyloxy compounds (5a-e) were prepared from alcohol (2b) and the corresponding acyl chlorides. In the antifungal activity test, p-tolyl compounds (4e, f) showed as good activity as butoconazole (4c).